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  • 251.
    Fornander, Lotta
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nyman, Torbjörn
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Hansson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Brismar, Tom
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Inter-hemispheric plasticity in patients with median nerve injury2016In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 628, p. 59-66Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured amp;gt;2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.21 +/- 0.15) compared to healthy controls (0.60 +/- 0.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with changes in the afferent signal inflow to the contralateral primary somatosensory cortex.

  • 252.
    Forsberg, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Björkstén, Bengt
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.2014In: Clinical and translational allergy, ISSN 2045-7022, Vol. 4, p. 1-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mice models indicate that intact Toll like receptor (TLR) signaling may be essential for the allergy protective effects of diverse bacterial exposure observed in clinical trials and epidemiological studies. Probiotic supplementation with Lactobacillus reuteri from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at two years (ClinicalTrials.gov NCT01285830). The effect of this supplementation on innate immune responses to bacterial products and the expression of associated TLRs were explored.

    METHODS: Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 infants and cultured with TLR2, 4 and 9 ligands. Cytokine and chemokine secretion was determined as well as TLR2, 4 and 9 mRNA expression.

    RESULTS: Probiotic supplementation was associated with decreased LTA (lipoteichoic acid) induced CCL4, CXCL8, IL-1β and IL-6 responses at 12 months and decreased CCL4 and IL-1β secretion at 24 months. TLR2 mRNA expression was not affected by probiotic treatment.

    CONCLUSIONS: Decreased responses to TLR2, the main receptor for LTA from Gram positive bacteria, in probiotic treated children seem to be dependent on factors downstream of TLR mRNA expression.

  • 253.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra AB, Linköping, Sweden.
    Lindblom, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Quick, Petter
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gauffin, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Quantitative analysis of the patellofemoral motion pattern using semi-automatic processing of 4D CT data2016In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 11, no 9, p. 1731-1741Article in journal (Refereed)
    Abstract [en]

    To present a semi-automatic method with minimal user interaction for quantitative analysis of the patellofemoral motion pattern. 4D CT data capturing the patellofemoral motion pattern of a continuous flexion and extension were collected for five patients prone to patellar luxation both pre- and post-surgically. For the proposed method, an observer would place landmarks in a single 3D volume, which then are automatically propagated to the other volumes in a time sequence. From the landmarks in each volume, the measures patellar displacement, patellar tilt and angle between femur and tibia were computed. Evaluation of the observer variability showed the proposed semi-automatic method to be favorable over a fully manual counterpart, with an observer variability of approximately 1.5 for the angle between femur and tibia, 1.5 mm for the patellar displacement, and 4.0-5.0 for the patellar tilt. The proposed method showed that surgery reduced the patellar displacement and tilt at maximum extension with approximately 10-15 mm and 15-20 for three patients but with less evident differences for two of the patients. A semi-automatic method suitable for quantification of the patellofemoral motion pattern as captured by 4D CT data has been presented. Its observer variability is on par with that of other methods but with the distinct advantage to support continuous motions during the image acquisition.

  • 254.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Editorial Material: Invited commentary: nutrition during growth and reproduction: studies demonstrating possibilities and difficulties2014In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 7, no 23484Article in journal (Other academic)
    Abstract [en]

    n/a

  • 255.
    Forsum, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Flinke Carlsson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Henriksson, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Henriksson, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
    Total body fat content versus BMI in 4-year-old healthy Swedish children.2013In: Journal of Obesity, ISSN 2090-0708, E-ISSN 2090-0716, Vol. 2013, article id 206715Article in journal (Refereed)
    Abstract [en]

    Childhood overweight and obesity, a worldwide problem, is generally identified using BMI (body mass index). However, this application of BMI has been little investigated in children below 5 years of age due to a lack of appropriate methods to assess body composition. Therefore, we used air displacement plethysmography (ADP) to study 4.4-year old boys and girls since this method is accurate in young children if they accept the requirements of the measurement. The purpose was to analyze the relationship between BMI and body fat in these children. Body composition was assessed in 76 (43 boys, 33 girls) of the 84 children brought to the measurement session. Boys and girls contained 25.2 ± 4.7 and 26.8 ± 4.0% body fat, respectively. BMI-based cut-offs for overweight could not effectively identify children with a high body fat content. There was a significant (P < 0.001) but weak (r = 0.39) correlation between BMI and body fat (%). In conclusion, requirements associated with a successful assessment of body composition by means of ADP were accepted by most 4-year-olds. Furthermore, BMI-based cut-offs for overweight did not effectively identify children with a high body fatness and BMI explained only a small proportion of the variation in body fat (%) in this age group.

  • 256.
    Forsum, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Henriksson, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska Institute, Novum, Sweden.
    The Two-Component Model for Calculating Total Body Fat from Body Density: An Evaluation in Healthy Women before, during and after Pregnancy2014In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 6, no 12, p. 5888-5899Article in journal (Refereed)
    Abstract [en]

    A possibility to assess body composition during pregnancy is often important. Estimating body density (D-B) and use the two-component model (2CM) to calculate total body fat (TBF) represents an option. However, this approach has been insufficiently evaluated during pregnancy. We evaluated the 2CM, and estimated fat-free mass (FFM) density and variability in 17 healthy women before pregnancy, in gestational weeks 14 and 32, and 2 weeks postpartum based on D-B (underwater weighing), total body water (deuterium dilution) and body weight, assessed on these four occasions. TBF, calculated using the 2CM and published FFM density (TBF2CM), was compared to reference estimates obtained using the three-component model (TBF3CM). TBF2CM minus TBF3CM (mean +/- 2SD) was -1.63 +/- 5.67 (p = 0.031), -1.39 +/- 7.75 (p = 0.16), -0.38 +/- 4.44 (p = 0.49) and -1.39 +/- 5.22 (p = 0.043) % before pregnancy, in gestational weeks 14 and 32 and 2 weeks postpartum, respectively. The effect of pregnancy on the variability of FFM density was larger in gestational week 14 than in gestational week 32. The 2CM, based on D-B and published FFM density, assessed body composition as accurately in gestational week 32 as in non-pregnant adults. Corresponding values in gestational week 14 were slightly less accurate than those obtained before pregnancy.

  • 257.
    Forsum, Elisabet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Olhager, Elisabeth
    Lund University, Sweden.
    Törnqvist, Caroline
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    An Evaluation of the Pea Pod System for Assessing Body Composition of Moderately Premature Infants2016In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 8, no 4, p. 238-Article in journal (Refereed)
    Abstract [en]

    (1) Background: Assessing the quality of growth in premature infants is important in order to be able to provide them with optimal nutrition. The Pea Pod device, based on air displacement plethysmography, is able to assess body composition of infants. However, this method has not been sufficiently evaluated in premature infants; (2) Methods: In 14 infants in an age range of 3-7 days, born after 32-35 completed weeks of gestation, body weight, body volume, fat-free mass density (predicted by the Pea Pod software), and total body water (isotope dilution) were assessed. Reference estimates of fat-free mass density and body composition were obtained using a three-component model; (3) Results: Fat-free mass density values, predicted using Pea Pod, were biased but not significantly (p &gt; 0.05) different from reference estimates. Body fat (%), assessed using Pea Pod, was not significantly different from reference estimates. The biological variability of fat-free mass density was 0.55% of the average value (1.0627 g/mL); (4) Conclusion: The results indicate that the Pea Pod system is accurate for groups of newborn, moderately premature infants. However, more studies where this system is used for premature infants are needed, and we provide suggestions regarding how to develop this area.

  • 258.
    Fransen, Jian
    et al.
    Uppsala University, Sweden.
    Huss, Fredrik R. M.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Surveillance of antibiotic susceptibility in a Swedish Burn Center 1994-20122016In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 42, no 6, p. 1295-1303Article in journal (Refereed)
    Abstract [en]

    Patients with burn trauma are at risk for infections caused by antibiotic resistant bacteria (ABR) with subsequent increase in morbidity and mortality. As part of the Swedish strategic program against antibiotic resistance in intensive care (ICU-Strama), we have surveyed the distribution of species and ABR in isolates from patients admitted to a Swedish burn center at Linkoping University Hospital from 1994 through 2012. In an international comparison Strama has been successful in reducing the antibiotic consumption among animals and humans in primary care. The aim of this study was to investigate the antibiotic consumption pressure and resistance rates in a Swedish burn unit. Methods: Microbiology data, total body surface area (TBSA), patient days, and mortality were collected from a hospital database for all patients admitted to the Burn Center at the University Hospital of Linkoping from April 1994 through December 2012. Results: A total of 1570 patients were admitted with a mean annual admission rate of 83 patients (range: 57-152). 15,006 microbiology cultures (approximately 10 per patient) were collected during the study period and of these 4531 were positive (approximately 3 per patient). The annual mean total body surface area (TBSA) was 13.4% (range 9.5-18.5) with an annual mortality rate of 5.4% (range 1-8%). The MRSA incidence was 1.7% (15/866) which corresponds to an MRSA incidence of 0.34/1000 admission days (TAD). Corresponding figures were for Escherichia coli resistant to 3rd generation cephalosporins (ESBL phenotype) 8% (13/170) and 0.3/TAD, Klebsiella spp. ESBL phenotype 5% (6/134) and 0.14/TAD, carbapenem resistant Pseudomonas aeruginosa 26% (56/209) and 1.28/TAD, and carbapenem resistant Acinetobacter spp. 3% (2/64) and 0.04/TAD. Conclusions: Our results show a sustained low risk for MRSA and high, although not increasing, risk for carbapenem resistant P. aeruginosa. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.

  • 259.
    Franzen, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Tibbling, Lita
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Is the severity of gastroesophageal reflux dependent on hiatus hernia size?2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 6, p. 1582-1584Article in journal (Refereed)
    Abstract [en]

    AIM:

    To determine if the severity of gastroesophageal reflux disease is dependent on the size of a hiatus hernia.

    METHODS:

    Seventy-five patients with either a small (n = 25), medium (n = 25) or large (n = 25) hiatus hernia (assessed by high resolution esophageal manometry) were investigated using 24-h esophageal monitoring and a self-assessed symptom questionnaire. The questionnaire comprised the following items, each graded from 0 to 3 according to severity: heartburn; pharyngeal burning sensation; acid regurgitation; and chest pain.

    RESULTS:

    The percentage total reflux time was significantly longer in the group with hernia of 5 cm or more compared with the group with a hernia of < 3 cm (P < 0.002), and the group with a hernia of 3 to < 5 cm (P < 0.04). Pharyngeal burning sensation, heartburn and acid regurgitation were more common with large hernias than small hernias, but the frequency of chest pain was similar in all three hernia groups.

    CONCLUSION:

    Patients with a large hiatus hernia are more prone to have pathological gastroesophageal reflux and to have more acid symptoms than patients with a small hiatus hernia. However, it is unlikely that patients with an absence of acid symptoms will have pathological reflux regardless of hernia size.

  • 260.
    Frisk, Jessica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ingvar, Martin
    Karolinska Institute, Sweden .
    Spetz, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    How long do the effects of acupuncture on hot flashes persist in cancer patients?2014In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 22, no 5, p. 1409-1415Article, review/survey (Refereed)
    Abstract [en]

    Purpose Acupuncture has been suggested as therapy for hot flashes in women with breast cancer and men with prostate cancer. In this systematic review, we sought to evaluate the long-term effects on vasomotor symptoms after the end of a defined treatment period of acupuncture in women with breast cancer and men with prostate cancer. Methods A literature search revealed 222 articles within the field. With defined exclusion criteria, we identified 17 studies. We also used the Jadad quality score and identified seven studies with a score of at least 3. Results Six of seven identified studies qualified for inclusion in an analysis that measured frequency of hot flashes weighted in relation to number of patients (n=172). The average reduction from baseline to end of acupuncture (ranging between 5 and 12 weeks of treatment) showed 43.2 % reduction of hot flashes. At the last follow-up (mean 5.8 months, range 39 months) after the end of therapy, the weighted reduction from baseline was sustained at 45.6 % in the 153 of 172 patients (89 %) who were followed up. Conclusions Data from six prospective analyzed studies indicate at least 3-month effects after the end of acupuncture treatment for flashes in women with breast cancer and men with prostate cancer. However, larger randomized trials with long-term follow-up will be needed to confirm these preliminary findings.

  • 261.
    Gabrielson, Marike
    et al.
    University of Örebro, Sweden; Karolinska Institute, Sweden.
    Reizer, Edwin
    University of Örebro, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Tina, Elisabet
    University of Örebro, Sweden.
    Mitochondrial regulation of cell cycle progression through SLC25A432016In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 469, no 4, p. 1090-1096Article in journal (Refereed)
    Abstract [en]

    An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclear Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G(1)-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G(1)-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. (C) 2015 Elsevier Inc. All rights reserved.

  • 262.
    Garvin, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Oda, Husam
    Cty Hosp Ryhov, Sweden; Umea Univ, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Lindström, Annelie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Shabo, Ivan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery2018In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 144, no 7, p. 1253-1263Article in journal (Refereed)
    Abstract [en]

    Cancer cell fusion with macrophages results in highly tumorigenic hybrids that acquire genetic and phenotypic characteristics from both maternal cells. Macrophage traits, exemplified by CD163 expression, in tumor cells are associated with advanced stages and poor prognosis in breast cancer (BC). In vitro data suggest that cancer cells expressing CD163 acquire radioresistance. Tissue microarray was constructed from primary BC obtained from 83 patients treated with breast-conserving surgery, 50% having received postoperative radiotherapy (RT) and none of the patients had lymph node or distant metastasis. Immunostaining of CD163 in cancer cells and macrophage infiltration (MI) in tumor stroma were evaluated. Macrophage:MCF-7 hybrids were generated by spontaneous in vitro cell fusion. After irradiation (0, 2.5 and 5 Gy gamma-radiation), both hybrids and their maternal MCF-7 cells were examined by clonogenic survival. CD163-expression by cancer cells was significantly associated with MI and clinicopathological data. Patients with CD163-positive tumors had significantly shorter disease-free survival (DFS) after RT. In vitro generated macrophage:MCF-7 hybrids developed radioresistance and exhibited better survival and colony forming ability after radiation compared to maternal MCF-7 cancer cells. Our results suggest that macrophage phenotype in tumor cells results in radioresistance in breast cancer and shorter DFS after radiotherapy.

  • 263.
    Gauffin, Emelie
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Uppsala University, Sweden.
    Öster, Caisa
    Uppsala University, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Gerdin, Bengt
    Uppsala University, Sweden.
    Ekselius, Lisa
    Uppsala University, Sweden.
    Health-related quality of life (EQ-5D) early after injury predicts long-term pain after burn2016In: BURNS, ISSN 0305-4179, Vol. 42, no 8, p. 1781-1788Article in journal (Refereed)
    Abstract [en]

    Background: Chronic pain after burn can have severe physical and psychological effects on former patients years after the initial injury. Although the issue of pain after burn has gained increased attention over the past years, prospective, longitudinal studies are scarce. Our aim was to prospectively investigate consecutive burn patients for pain severity over time and to evaluate the prevalence and characteristics of post-burn pain to 2-7 years after the burn. As an additional aim, the effects of burn and individual-related factors, especially health related Quality of Life (HRQoL), were investigated. Method: Sixty-seven consecutive burn patients were assessed during acute care at 3, 6, 12 and 24 months, as well as at 2-7 years post-burn. HRQoL, symptoms of post-traumatic stress disorder (PTSD) and other psychiatric disorders were investigated. During the interviews that took place 2-7 years after the injury (mean 4.6 1.9 years), current chronic post-burn pain was assessed using the Brief Pain Inventory-Short Form (BPI-SF). Results: One-third of the patients still reported pain 2-7 years after the injury. Pain severity and interference with daily life were mainly mild to moderate though they were found to be associated with significantly lower HRQoL. Chronic pain after bum was associated with both burn- and individual-related factors. In logistic regression analysis HRQoL at 3 and 12 months and symptoms of PTSD at 12 months were independent factors in predicting chronic pain after burn. Conclusion: Pain after burn becomes a chronic burden for many former burn patients and decreases HRQoL. A novel finding in this study was that HRQoL assessed early after burn was a predictor for the development of chronic pain. This finding may help to predict future pain problems and serve as an indicator for pain preventive measures. (C) 2016 The Authors. Published by Elsevier Ltd.

  • 264.
    Gauffin, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tagesson (Sonesson), Sofi
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Meunier, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Magnusson, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Kvist, Joanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Knee arthroscopic surgery is beneficial to middle-aged patients with meniscal symptoms: a prospective, randomised, single-blinded study2014In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 22, no 11, p. 1808-1816Article in journal (Refereed)
    Abstract [en]

    Objective: There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy. Method: 150 out of 179 eligible patients, aged 45 to 64 (mean: 54 +/- 5), symptom duration more than 3 months and standing X-ray with Ahlback grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN). Results: In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P = 0.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results. Conclusion: Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme. Patients age or symptom history (i.e., mechanical symptoms or acute onset of symptoms) didnt affect the outcome.

  • 265.
    Gauthier Westergård, Veronica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barnets rätt att komma till tals i familjebehandling. Familjebehandlarnas röster om Barnkonventionens artikel 12 i praktiken.2014Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of the study was to investigate if the article 12 of the Convention of the Rights of the Child to be heard is applied in family treatment by making a pilot study. Family practitioners within the municipal outpatients care had to answer how they did involve the children, the manner in which children were heard and if there were times when children should not be participate in family treatment. To get answers to these questions a semi-structured survey was made. The selected theory was systems theory.  The study also included the Convention of the Rights of the Child, family treatment and BBIC. The results showed that family practitioners used various methods to get children to be heard. There was a lot of flexibility around these practices making children involved and creating the opportunity to get children to talk. There were times when children should not participate in family therapy for example when parents had their own difficulties and when it was a predominantly adult problem.

  • 266.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    James, A. Rani
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Liljenstrom, R.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Muraro, A.
    Padua University Hospital, Italy .
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    The Allergic Airway Inflammation Repository - a user-friendly, curated resource of mRNA expression levels in studies of allergic airways2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 8, p. 1115-1117Article in journal (Refereed)
    Abstract [en]

    Public microarray databases allow analysis of expression levels of candidate genes in different contexts. However, finding relevant microarray data is complicated by the large number of available studies. We have compiled a user-friendly, open-access database of mRNA microarray experiments relevant to allergic airway inflammation, the Allergic Airway Inflammation Repository (AAIR, http://aair.cimed.ike.liu.se/). The aim is to allow allergy researchers to determine the expression profile of their genes of interest in multiple clinical data sets and several experimental systems quickly and intuitively. AAIR also provides quick links to other relevant information such as experimental protocols, related literature and raw data files.

  • 267.
    Gerdin, Bengt
    et al.
    Uppsala University Hospital.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Professor Gösta Arturson (1927–2013): Obituary2013In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 39, no 8, p. 1654-1655Article in journal (Other (popular science, discussion, etc.))
  • 268.
    Gerdin, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Department of Surgery, Höglandssjukhuset, Eksjö, Sweden.
    Eriksson, Anders S.
    Sahlgrens University Hospital, Sweden.
    Olaison, Gunnar
    Northern Hospital Zeeland, Denmark.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 1, p. 50-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

  • 269.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Medullary thyroid carcinoma - Characteristics, diagnostics, therapy and follow-up [Medulläres Schilddrüsenkarzinom - Besonderheiten, Diagnostik, Therapie und Nachsorge]2012In: Klinikarzt, ISSN 0341-2350, Vol. 41, no 10, p. 476-480Article in journal (Refereed)
    Abstract [en]

    Medullary thyroid carcinoma (MTC) is a rare malignant tumor of the thyroid gland, it probably accounts for about 3 - 8% of all thyroids cancers. In contrast to the majority of thyroid cancers that develop from thyreocytes, MTC has its origins in parafollicular C cells. Among others, these cells synthesize calcitonin which thus represents a very sensitive tumor marker. MTC is not responsive to the usually employed conventional radio-iodine therapy because C cells, in contrast to threocytes, do not take up iodine. This fact places additional demands on surgical treatment. The management of MTCs that are not suitable for operative treatment because of their inoperable nature or, respectively, due to the presence of distant disseminated metastases is a hot topic of current intensive research. © Georg Thieme Verlag KG · Stuttgart · New York.

  • 270.
    Ginning, Lise-Lotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Familjearbete på institution förändrar relationer och minskar konflikter.2014Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this essay has been find out if working with a family which has its younger members placed in an institution, SiS Youthhome Folåsa, will affect the adolescents experience of anxiety and problems within their family and their mental health.

    Through an analysis of the interviews given to the adolescents upon arrival and departure to the facility and later on in the follow up interview, I have tried find the answers to the essay`s questions.

    When the adolescents themselves have to assess their experience, they find that life is better or much better in most areas that ADAD intends to explore. It shows that, one year after they have been discharged, the adolescents experience less conflicts in their families and they also worry less about family related problems. However, their apprehension of their mental health has increased somewhat compared to how they felt before the treatment.

    The majority of the adolescents consider that they got the help they needed with the problem they had and only two (2/26) of the participants in this study were placed at another institution after their stay at Folåsa.

  • 271.
    Ginstman, Charlotte
    et al.
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Frisk, Jessica
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ottosson, Johan
    University of Örebro, Sweden.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Contraceptive Use Before and After Gastric Bypass: a Questionnaire Study2015In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 11, p. 2066-2070Article in journal (Refereed)
    Abstract [en]

    At present, women are recommended to avoid pregnancy 12-18 months after bariatric surgery. Our aim in this study was to describe patterns of contraceptive use before and after gastric bypass in Sweden, and to describe the contraceptive counseling given preoperatively to women undergoing gastric bypass. In October 2012, a questionnaire was sent to 1000 Swedish women who all had undergone gastric bypass during 2010. The women had been included in the Scandinavian Obesity Surgery Register at time of surgery. The main outcome measures were patterns of use of contraception before and after bariatric surgery. The response rate was 57 %. The most commonly used contraceptive methods were intrauterine devices, 29 % preoperatively and 26 % postoperatively even though there was a postoperative switch from the copper intrauterine device to the levonorgestrel intrauterine system. Thirty percent did not use any contraceptive during the first 12 months after surgery. Sixty percent of the responders were aware of the recommendations to avoid pregnancy after surgery. Many women who undergo bariatric surgery are not using any contraceptive method despite the recommendation that they should avoid pregnancy for at least 12 months. There is a great need to improve contraceptive counseling for this growing group of women.

  • 272.
    Gjessing, Kristian
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Torgé, Cristina Joy
    Linköping University, Department of Social and Welfare Studies, NISAL - National Institute for the Study of Ageing and Later Life. Linköping University, Faculty of Arts and Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dahlberg, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Improvement of quality and safety in health care as a new interprofessional learning module – evaluation from students2014In: Journal of Multidisciplinary Healthcare, ISSN 1178-2390, E-ISSN 1178-2390, no 7, p. 341-347Article in journal (Refereed)
    Abstract [en]

    Background: Interprofessional teamwork is in many ways a norm in modern health care, and needs to be taught during professional education.

    Description: This study is an evaluation of a newly introduced and mandatory learning module where students from different health profession programs used Improvement of Quality and Safety as a way to develop interprofessional competence in a real-life setting. The intention of this learning module was to integrate interprofessional teamwork within the students' basic education, and to give students a basic knowledge about Improvement of Quality and Safety. This report focuses on evaluations from the participating students (n=222), mainly medical and nursing students.

    Materials and methods: To evaluate this new learning module, a questionnaire was developed and analyzed using a mixed methods design, integrating both qualitative and quantitative methods. The evaluation addressed learning concepts, learning objectives, and interprofessional and professional development.

    Results and conclusion: A majority of students responded positively to the learning module as a whole, but many were negative towards specific parts of the learning module and its implementation. Medical students and male students were less positive towards this learning module. Improvements and alterations were suggested. 

  • 273. Glimelius, Bengt
    et al.
    Dahl, Olav
    Cedermark, Björn
    Jakobsen, Anders
    Bentzen, Sören M
    Starkhammar, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Grönberg, Henrik
    Hultborn, Ragnar
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Påhlman, Lars
    Tveit, Kjell-Magne
    Adjuvant chemotherapy in colorectal cancer: A joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 904-912Article in journal (Refereed)
    Abstract [en]

    Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444, 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to ±levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations. © 2005 Taylor & Francis.

  • 274.
    Gnosa, Sebastian
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The incidence and death rate for colorectal cancer (CRC) decreased during the last decades as a result of improved diagnosis and treatment. However, CRC is still the third most common cancer in the world, and is responsible for about 700 000 deaths per year worldwide. Therefore, it is important to understand the mechanisms of the disease, and to find molecular markers in order to further improve prognosis, and to develop new treatment strategies. Astrocyte elevated gene-1 (AEG-1), encoded by the MTDH gene, is upregulated in a variety of cancers. AEG-1 is involved in cell survival, proliferation, migration, invasion, metastasis,  angiogenesis, and apoptosis.

    The aim of this thesis was to investigate the role of AEG-1 in CRC development and the impact of AEG-1 on the response of radiation treatment. The AEG-1 expression, analysed in different CRC patient cohorts in paper I and III, was increased in the tumour tissue compared with the normal mucosa, and higher in the lymph node and liver metastases. Expression analyses in normal and cancer cell lines confirmed these results. In paper II, sequencing of the complete coding sequence of the MTDH gene in 356 patients revealed 50 single nucleotide variants of which 29 were novel. Eight exonic variants were detected, including three frameshift variants which were probably pathogenic, and two missense variants located in functional protein regions. There was no correlation of the MTDH variants or AEG-1 expression with the patient survival. In paper III, we also investigated the impact of AEG-1 on the response to radiation treatment. AEG-1 knockdown decreased the cellular survival upon radiation in several colon cancer cell lines. The AEG-1 expression was furthermore analysed in patients, which were randomised to either surgery alone or preoperative radiotherapy (RT), followed by surgery. The rectal cancer patients with high AEG-1 expression treated with RT had a significantly higher risk of developing distant recurrence and had a worse disease free survival, likely due to the metastasis promoting properties of AEG-1. In paper IV, the impact of AEG-1 knockdown and radiation on migration and invasion was analysed in colon cancer cell lines in vitro  and in a novel zebrafish model in vivo. AEG-1 knockdown decreased migration and invasion, and radiation-enhanced migration and invasion in the cell lines tested.

    In conclusion, our data suggest that AEG-1 is involved in CRC development, while MTDH gene variants probably not have a high clinical importance in CRC. Furthermore, AEG-1 is a promising radiosensitising target and a valuable prognostic marker in CRC. We further showed that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced cell migration and invasion.

  • 275.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dahl Ejby Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 49, p. 81634-81644Article in journal (Refereed)
    Abstract [en]

    Background Radiotherapy is a well-established anti-cancer treatment. Although radiotherapy has been shown to significantly decrease the local relapse in rectal cancer patients, the rate of distant metastasis is still very high. Several studies have shown that radiation enhances migration and invasion both in vitro and in vivo. The aim of this study was to evaluate whether AEG-1 is involved in radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.

    Materials and Methods We evaluated the involvement of AEG-1 in migration and invasion and radiation-enhanced migration and invasion by Boyden chamber assay in three colon cancer cell lines and respective AEG-1 knockdown cell lines. Furthermore, we injected the cells in zebrafish embryos and evaluated the amount of disseminated cells into the tail.

    Results Migration and invasion was decreased in all the AEG-1 knockdown cell lines. Furthermore, radiation enhanced migration and invasion, while AEG-1 knockdown could abolish this effect. The results from the zebrafish model confirmed the results obtained in vitro. MMP-9 secretion and expression were decreased in AEG-1 knockdown cells.

    Conclusion Our results demonstrate that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced migration and invasion. We speculate that this is done via the downregulation of the intrinsic or radiation-enhanced MMP-9 expression. The zebrafish model can be used to study early events in radiation-enhanced invasion.

  • 276.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ticha, Ivana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    MTDH genetic variants in colorectal cancer patients2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cancer worldwide and accounts for around 8.5% of all cancer related death. The colorectal carcinogenesis is a complex process of genetic alterations. For better prognosis it is very important to understand the composition of genetic alterations in a tumor. Astrocyte elevated gene-1 (AEG-1) has been shown to be overexpressed in CRC and had prognostic significance. The aim of this study was to determine the frequency and the spectrum of MTDH variants, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. We detected 42 intronic variants, whereby 25 were novel. Furthermore, we found eight exonic variants of which four, one missense (c.977C>G) and three frameshift mutations (c.533delA, c.1731delA, c.1340dupA), were novel. In silico prediction analyses revealed that four variants c.232G>T, c.533delA, c.1340dupA and c.1731delA were deleterious. There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. The detection of pathogenic mutations and alterations in functional protein domains suggest their involvement in tumorigenesis, although none of the variants had prognostic potential.

  • 277.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, H.
    University of Örebro, Sweden .
    Brodin Patcha, Veronika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health and Society. Linköping University, Faculty of Health Sciences.
    Adell, G.
    Karolinska University Hospital, Sweden .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial2014In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, no 1, p. 166-173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.

    METHODS:

    The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay.

    RESULTS:

    The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.

    CONCLUSIONS:

    The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.

  • 278.
    Gonzalez-Arto, Marta
    et al.
    University of Zaragoza, Spain.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez-Pastor, Felipe
    University of Leon, Spain.
    Fernandez-Alegre, Estela
    University of Leon, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Miro, Jordi
    University of Barcelona, Spain.
    Rigau, Teresa
    University of Barcelona, Spain.
    Rodriguez-Gil, Joan E.
    University of Barcelona, Spain.
    Perez-Pe, Rosaura
    University of Zaragoza, Spain.
    Muino-Blanco, Teresa
    University of Zaragoza, Spain.
    Cebrian-Perez, Jose A.
    University of Zaragoza, Spain.
    Casao, Adriana
    University of Zaragoza, Spain.
    Melatonin receptors MT1 and MT2 are expressed in spermatozoa from several seasonal and nonseasonal breeder species2016In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 86, no 8, p. 1958-1968Article in journal (Refereed)
    Abstract [en]

    Melatonin is a ubiquitous and multipurpose molecule, and one of its roles is to regulate reproduction in some seasonal mammals. Our group has previously reported the variation in the melatonin levels in ram seminal plasma along the year and identified MT1 and MT2 receptors in ram spermatozoa. The objective of this study was to elucidate whether the presence of melatonin receptors (MT1 and MT2) in the sperm plasma membrane, and melatonin in the seminal plasma is related to seasonal breeding. For this purpose, the presence of melatonin receptors and tseasonal breeder (epididymal spermatozoa); bull as a conventional nonseasonhe levels of melatonin in seminal plasma have been examined in several species: donkey and stallion as long-day breeders; red deer as a wild, short-day, highly al breeder; boar as a seasonal breeder, under management techniques; and dog as possible a seasonal breeder not regulated by melatonin. We have detected measurable levels of melatonin in the seminal plasma of all ejaculated semen samples (from donkey, stallion, boar, bull, and dog). Also, and for the first time, we have demonstrated the presence of MT1 and MT2 melatonin receptors in the spermatozoa of all these species, regardless their type of reproduction or sperm source (ejaculated or epididymal), using indirect immunofluorescence techniques and Western blotting. Our findings suggest that melatonin and melatonin receptors may be universally distributed in the reproductive system of mammals and that the sperm melatonin receptors cells may not be necessarily related with seasonal reproduction. Furthermore, the presence of MT1 at the cytoplasmic droplet in immature ejaculated stallion spermatozoa found in one sample and epididymal red deer spermatozoa suggests that melatonin may be involved in specific functions during spermatogenesis and sperm maturation, like protecting spermatozoa from oxidative damage, this activity being mediated through these receptors. (C) 2016 Elsevier Inc. All rights reserved.

  • 279.
    Gothlin Eremo, Anna
    et al.
    University of Örebro, Sweden.
    Tina, Elisabet
    Örebro University Hospital, Sweden.
    Wegman, Pia
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fransen, Karin
    University of Örebro, Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Wingren, Sten
    University of Örebro, Sweden.
    HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen2015In: International Journal of Oncology, ISSN 1019-6439, Vol. 47, no 4, p. 1311-1320Article in journal (Refereed)
    Abstract [en]

    The human epidermal growth factor receptor (HER) 4 is a relative of HER2 and has been associated to endocrine breast cancer and prediction of tamoxifen response. In addition to PI3K/Akt and MAPK pathway activation, ligand binding to HER4 triggers proteolytic cleavage and release of an intracellular receptor domain (4ICD) with signaling properties. The aim of the present study was to analyze HER4 protein expression and intracellular localization in breast cancer tissue from patients randomized to treatment with or without adjuvant tamoxifen. To investigate HER4 expression and localization in response to estradiol (E2) and 4-hydroxytamoxifen (4-OHT) exposure, we also performed in vitro studies. Cytoplasmic, nuclear and membrane expression of HER4 protein was evaluated by immunohistochemical staining in tumor tissue from 912 breast cancer patients. Three different breast epithelia cancer cell lines were exposed to E2 and 4-OHT and mRNA expression was analyzed using qPCR. Further, nuclear and cytoplasmic proteins were separated and analyzed with western blotting. We found an association between nuclear HER4 protein expression and ER-positivity (P=0.004). Furthermore, significant association was found between cytoplasmic HER4 and ER-negativity (Pless than0.0005), PgR-negativity (Pless than0.0005), tumor size greater than20 mm (P=0.001) and HER2-negativity (P=0.008). However, no overall significance of HER4 on recurrence-free survival was found. After E2 exposure, HER4 mRNA and protein expression had decreased in two cell lines in vitro yet no changes in nuclear or cytoplasmic protein fractions were seen. In conclusion, nuclear HER4 seem to be co-located with ER, however, we did not find support for overall HER4 expression in independently predicting response of tamoxifen treatment. The possible influence of separate isoforms was not tested and future studies may further evaluate HER4 significance.

  • 280.
    Gothlin Eremo, Anna
    et al.
    University of Örebro, Sweden .
    Wegman, Pia
    University of Örebro, Sweden .
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fornander, Tommy
    Stockholm South Gen Hospital, Sweden .
    Wingren, Sten
    University of Örebro, Sweden .
    Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients2013In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 4, p. 1467-1474Article in journal (Refereed)
    Abstract [en]

    Reduced or absent Wwox expression has recently been associated with tamoxifen resistance in breast cancer and has also been proposed as a candidate predictive marker for treatment. We aimed to investigate the correlation of Wwox expression with the outcome of tamoxifen treatment by examining tissues from 912 randomized breast cancer patients. Paraffin-embedded tissues from patient tumors were arranged on tissue microarray, and Wwox protein was stained using immunohistochemistry. After microscopic examination, the results were analyzed with Cox regression, Kaplan-Meier survival curves and the log-rank test. In the group of cases having a tumor absent for Wwox expression, there was no difference in recurrence-free survival between treated and untreated patients (P=0.81). For treated cases with a tumor expressing moderate or strong Wwox protein, recurrence-free survival was improved (P=0.001 and P=0.003, respectively). The test for interaction between Wwox and treatment response demonstrated a decreased risk of recurrence for treated patients with a moderate or strong Wwox expression (HR=0.31, 95% CI 0.10-0.98 and HR=0.28, 95% CI 0.08-0.97, respectively). Our results indicate that patients with high expression of Wwox may gain more benefit from treatment with tamoxifen.

  • 281.
    Grahnat, Carl Johan
    et al.
    County Hospital Ryhov, Sweden.
    Herard, Sebastian
    County Hospital Ryhov, Sweden.
    Ackzell, Annicka
    County Hospital Ryhov, Sweden.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    High Probability of an Underlying Colorectal Cancer Among Patients Treated for Acute Diverticulitis. A Population-Based Cohort Follow-Up Study2016In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 40, no 9, p. 2283-2288Article in journal (Refereed)
    Abstract [en]

    Introduction Patients treated conservatively for acute diverticulitis (AD) are recommended colonic assessment to rule out an underlying Colorectal cancer (CRC). This has been questioned in patients with a CT diagnosis of uncomplicated AD. We analyzed the frequency of CRC and compared the characteristics of the CRC patients with controls. Method A cohort of patients treated conservatively for AD during 2005-2011 was identified through an administrative database. Patients diagnosed with CRC within 1 year after the index admission and four randomly selected controls were identified. The patients files were reviewed to verify the diagnosis and obtain information about the clinical characteristics and the management. A blinded review was performed of CT examinations. The expected number of CRC was calculated from age, sex, and period-specific incidence data. The characteristics of the CRC patients were compared with the controls in a nested case-control study. Results 890 patients (298 men and 592 women) were treated conservatively for AD. 12 patients were diagnosed with CRC within 1 year, and ten of them in the sigmoid, giving a Standardized Incidence Ratio of 20.0 (95 % CI 10.2-35.7, pamp;lt;0.001) for sigmoidal cancer. All CRC patients were aged over 70 years. The cancer was missed in six CT scans at the primary reading and in five at the blinded review. Conclusion Patients conservatively treated for AD are at high risk for an underlying CRC, especially if older than 70 years, which motivates routine follow-up. A CT diagnosis of uncomplicated AD does not rule out CRC.

  • 282.
    Granbom, Elin
    et al.
    Umeå University, Sweden; Ostersund Hospital, Sweden.
    Fernlund, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Pediatric Heart CenterLund University, Sweden.
    Sunnegardh, Jan
    Sahlgrenska University Hospital, Sweden.
    Lundell, Bo
    Karolinska University Hospital, Sweden.
    Naumburg, Estelle
    Umeå University, Sweden; Östersund Hospital, Sweden.
    Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study2016In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 37, no 6, p. 1098-1105Article in journal (Refereed)
    Abstract [en]

    Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006-2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.

  • 283.
    Granfors, Maria
    et al.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Augustin, Hanna
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Brekke, Hilda K
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    No association between use of multivitamin supplement containing vitamin D during pregnancy and risk of Type 1 Diabetes in the child2016In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 17, no 7, p. 525-530Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Sweden has the second highest incidence of type 1 diabetes in the world. Nutritional aspects in utero and in infancy affect the development. We conducted a survey to determine whether reported maternal use of vitamin D-containing micronutrient supplements during pregnancy was associated with the risk of developing type 1 diabetes in the child.

    METHODS:

    This report was based on data from the ABIS (All Babies In Southeast Sweden) study, with questionnaire data on 16 339 mother and infant pairs at birth and at 1-yr of age (n = 10 879), of whom 108 children were registered with type 1 diabetes before 14-16 yr of age. The questions 'during pregnancy, did you take any vitamin/mineral supplements?' and 'if yes, which? (open answer)' in addition to other lifestyle questions were answered. Logistic regression was performed with onset of type 1 diabetes as the dependent variable and vitamin D supplementation use as the independent variable, adjusted for relevant factors.

    RESULTS:

    Vitamin D supplementation during pregnancy was consumed by 9.3% of mothers whose children later got type1 diabetes and among 11.3% of those mothers whose children did not get type 1 diabetes (p = 0.532). No significant association was found between reported supplement intake of vitamin D during pregnancy and risk of type 1 diabetes, even when adjusting for factors which could influence the association.

    CONCLUSION:

    Maternal use of vitamin D-containing multivitamin supplements during pregnancy was not related to the risk of developing type 1 diabetes in children before 14-16 yr of age in Southeast of Sweden.

  • 284.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Mirghani, Rajaa A
    Karolinska University .
    Rymark, Per
    Västerås Hospital.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska University Hospital.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer2009In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 104, no 2, p. 130-137Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty-eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performed in vivo with quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activity in vivo affected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.

  • 285.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Mirghani, Rajaa A.
    Rymark, Per
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Pharmacogenetics of Paclitaxel in the Treatment of Ovarian Cancer – a Pilot Study in Preparation of Individualized Chemotherapy2007In: Clinical Cancer Research, ISSN 1078-0432Article in journal (Refereed)
  • 286.
    Gren Landell, Malin
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ekerfelt Allvin, Cornelia
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Bradely, Maria
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Teachers' views on risk factors for problematic school absenteeism in Swedish primary school students2015In: Educational Psychology in Practice, ISSN 0266-7363, E-ISSN 1469-5839, Vol. 31, no 4, p. 412-423Article in journal (Refereed)
    Abstract [en]

    In the present online survey, 158 teachers in regular and special education teaching in grades six to nine were asked to rate the importance of probable reasons for problematic school absenteeism. On average, the teachers estimated that among their students, 19 students had presented with problematic school absenteeism over the last five years. Teachers viewed school absenteeism as a multifactorial problem. Family factors were considered to contribute most and low mood or depression were rated as one of the five most contributing factors. Teachers in special education viewed school factors as more influential than teachers in mainstream education did (t156 = −3.94, p < 0.05). The current findings stress the importance of collaboration between the school, parents and the student to be able to address all factors that may lead to problematic school absenteeism.

  • 287.
    Grundström, Hanna
    et al.
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kjølhede, Preben
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Alehagen, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    “A challenge” – healthcare professionals' experiences when meeting women with symptoms that might indicate endometriosis2016In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 7, p. 65-69Article in journal (Refereed)
    Abstract [en]

    Objective

    The aim of the study was to identify and describe the experiences of healthcare professionals when meeting women with symptoms that might indicate endometriosis.

    Methods

    Semi-structured interviews were conducted with 10 gynecologists, six general practitioners and nine midwives working at one university hospital, one central hospital, one private gynecology clinic and five healthcare centers in south-east Sweden. The interviews were recorded and transcribed verbatim and analyzed using qualitative conventional content analysis.

    Results

    Three clusters were identified: the corroborating encounter, the normal variation of menstruation cycles, and the suspicion of endometriosis. The healthcare professionals tried to make a corroborating encounter by acknowledging the woman, taking time to listen, and giving an explanation for the problems. Healthcare professionals had different ways to determine what was normal as regards menstrual pain, ovulation pain and dyspareunia. They also needed to have the competence to act and react when the symptoms indicated endometriosis.

    Conclusions

    Meeting women with symptoms that might indicate endometriosis is challenging and demands a certain level of competence from healthcare professionals. Sometimes the symptoms are camouflaged as “normal” menstruation pain, making it hard to satisfy the needs of this patient group.

  • 288.
    Gudjonsson, Sigurdur
    et al.
    Skåne University Hospital, Sweden .
    Blackberg, Mats
    Helsingborg County Hospital, Sweden .
    Chebil, Gunilla
    Helsingborg County Hospital, Sweden .
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olsson, Hans
    Lund University, Sweden .
    Bendahl, Par-Ola
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Mansson, Wiking
    Skåne University Hospital, Sweden .
    Liedberg, Fredrik
    Skåne University Hospital, Sweden Vaxjo County Hospital, Sweden .
    The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)2012In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 110, no 2B, p. E41-E45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.

  • 289.
    Gudmundsson, Jens Kristjan
    et al.
    Eskilstuna Hospital, Sweden.
    Ajan, Aida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    The accuracy of fine-needle aspiration cytology for diagnosis of parotid gland masses: a clinicopathological study of 114 patients2016In: Journal of Applied Oral Science, ISSN 1678-7757, E-ISSN 1678-7765, Vol. 24, no 6, p. 561-567Article in journal (Refereed)
    Abstract [en]

    Objective: Fine-needle aspiration cytology is a valuable method for preoperative assessment of head and neck tumors. However, its accuracy in detection of salivary gland masses is controversial compared with other methods. The aim of this work was to evaluate the effectiveness and accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses. Material and Methods: Over a 10-year period, 126 parotid gland masses were resected. Retrospective chart reviews of 114 patients were performed. The results of FNAC and final histological diagnosis were compared and the accuracy of FNAC was determined. Results: Final histological evaluation revealed 11 malignant tumors and 103 benign lesions. Pleomorphic adenoma was the most common neoplasm (63%), followed by Warthins tumor (17.5%). The sensitivity of FNAC in detecting malignant tumors was 73% and the specificity was 97%. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 97%. The overall accuracy of FNAC in detecting parotid masses was 95%. False-negative diagnosis was found in mucoepidermoid carcinoma, acinic cell carcinoma, and epithelial-myoepithelial carcinoma whereas there was false-positive diagnosis in cases of pleomorphic adenoma and normal parotid gland tissue. Conclusion: FNAC is a reliable minimally invasive diagnostic method with a high sensitivity in diagnosis of lesions in parotid glands. The sensitivity of detection of malignant tumors in parotid glands was low due to the biopsy technique used, and depended on tumor location. Postoperative complications decreased after superficial parotidectomy.

  • 290.
    Gustafsson, Anna
    et al.
    Lund University, Sweden.
    Schilcher, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Grassi, Lorenzo
    Lund University, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Isaksson, Hanna
    Lund University, Sweden.
    Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture2016In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 88, p. 125-130Article in journal (Refereed)
    Abstract [en]

    Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healink. A patient specific finite element model was developed, based on clinical CT images and high resolution CT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% cif the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. (C) 2016 Elsevier Inc. All rights reserved.

  • 291.
    Gustafsson, Berit M.
    et al.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Högland Hospital, Sweden; Jönköping University, Sweden.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Proczkowska, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Hospital Jönköping, Sweden.
    The Strengths and Difficulties Questionnaire (SDQ) for preschool childrena Swedish validation2016In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 70, no 8, p. 567-574Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, 80-90% of children aged 1-5 years attend preschool, and that environment is well suited to identify behaviours that may be signs of mental health problems. The Strengths and Difficulties Questionnaire (SDQ) is a well-known short and structured instrument measuring child behaviours that indicate mental health problems well suited for preschool use.Aim: To investigate whether SDQ is a reliable and valid instrument for identifying behavioural problems in children aged 1-3 years and 4-5 years in a Swedish population, as rated by preschool teachers.Methods: Preschools situated in different sized municipalities in Sweden participated. The preschool teacher rated each individual child. Concurrent validity was tested using the Child-Teacher Report Form (C-TRF) and Child Engagement Questionnaire (CEQ). Exploratory factor analysis was conducted for age groups, 1-3 years and 4-5 years.Results: The preschool teachers considered most of the SDQ items relevant and possible to rate. For the children aged 1-3 years, the subscales Hyperactivity (Cronbach alpha=0.84, split half=0.73) and Conduct (Cronbach alpha=0.76, split half=0.80) were considered to be valid. For the age group 4-5 years, the whole original SDQ scale, 4-factor solution was used and showed reasonable validity (Cronbach alpha=0.83, split half=0.87).Conclusion: SDQ can be used in a preschool setting by preschool teachers as a valid instrument for identifying externalizing behavioural problems (hyperactivity and conduct problems) in young children.Clinical implications: SDQ could be used to identify preschool children at high-risk for mental health problems later in life.

  • 292.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Edström, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Tojo, James
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Kockum, Ingrid
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Olsson, Tomas
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Serra-Musach, Jordi
    IDIBELL, Spain .
    Bonifaci, Nuria
    IDIBELL, Spain .
    Angel Pujana, Miguel
    IDIBELL, Spain .
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment2014In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 17Article in journal (Refereed)
    Abstract [en]

    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

  • 293.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Liljenström, H. Robert I.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 313, article id 313ra178Article in journal (Refereed)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

  • 294.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barabasi, Albert-Laszlo
    Northeastern University, MA 02115 USA.
    Baranzini, Sergio
    University of Calif San Francisco, CA 94143 USA.
    Brunak, Soeren
    Technical University of Denmark, Denmark; University of Copenhagen, Denmark.
    Fan Chung, Kian
    University of London Imperial Coll Science Technology and Med, England.
    Federoff, Howard J.
    Georgetown University, DC 20057 USA.
    Gavin, Anne-Claude
    European Molecular Biol Lab, Germany.
    Meehan, Richard R.
    University of Edinburgh, Scotland.
    Picotti, Paola
    University of Zurich, Switzerland.
    Angel Pujana, Miguel
    Bellvitge Biomed Research Institute IDIBELL, Spain.
    Rajewsky, Nikolaus
    Max Delbruck Centre Molecular Med, Germany.
    Smith, Kenneth G. C.
    University of Cambridge, England; University of Cambridge, England.
    Sterk, Peter J.
    University of Amsterdam, Netherlands.
    Villoslada, Pablo
    Hospital Clin Barcelona, Spain; Hospital Clin Barcelona, Spain.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Modules, networks and systems medicine for understanding disease and aiding diagnosis2014In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 82Article, review/survey (Refereed)
    Abstract [en]

    Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.

  • 295.
    Göranson, Emma
    et al.
    Östergötlands Läns Landsting, Public Dental Health Care.
    Lundström, Fredrik
    Östergötlands Läns Landsting, Public Dental Health Care.
    Bågesund, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care.
    Outcome of orthodontic care and residual treatment need in Swedish 19-year-olds2014In: Swedish Dental Journal, ISSN 0347-9994, Vol. 38, no 3, p. 133-142Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to assess the outcome of orthodontic care in Linkoping, Sweden. The dental records of 207 (107 M,100 F) 19-year-olds registered at one public dental health clinic were studied. A clinical examination was performed where malocclusions were registered, where after residual orthodontic treatment need was measured using the Index of Complexity, Outcome and Need (ICON). The 19-year-olds also filled in a questionnaire regarding residual subjective orthodontic treatment demand. Differences between genders were analysed. One hundred and ten (47 M, 63 F) individuals (53.1%) had partaken in orthodontic consultations. Orthodontic appliance treatment had been received by 86 (38 M, 48 F) individuals (41.6%). A residual orthodontic treatment need was registered in 28 (22 M, 6 F) individuals (13.5%). Residual subjective orthodontic treatment demand was expressed by 9 (3 M, 6 F) individuals (4.3%). Eight (2 M, 6 F) of those had no residual treatment need. A higher (p=0.006) rate of females (63.0%) than males (44.0%) had participated in orthodontic consultations. The proportion of males (35.5%) who had experienced orthodontic treatment was not significantly lower (p=0.069) than among the females (48.0%). However, a lower (p=0.009) proportion of treated males (55.3%; n=21 out of 38) than of treated females (81.3%; n=39 out of 48) had received their treatment by orthodontic specialists. At 19 years of age, the proportion of males with residual treatment need (20.6%) was higher (p=0.002) than among the females (6.0%). Every patient with orthodontic treatment need and -demand at 19 years of age had previously been offered orthodontic treatment. The conclusion was drawn that the orthodontic care scheme had successfully diagnosed and treated orthodontic problems in the population. However, notable differences between genders regarding treatment modalities and the amount of residual treatment need at age 19 were found.

  • 296.
    Hagg, Mary
    et al.
    Hudiksvall Hospital, Sweden; Uppsala University, Sweden.
    Tibbling, Lita
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Franzen, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Esophageal dysphagia and reflux symptoms before and after oral IQoro(R) training2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 24, p. 7558-7562Article in journal (Refereed)
    Abstract [en]

    AIM: To examine whether muscle training with an oral IQoro(R) screen (IQS) improves esophageal dysphagia and reflux symptoms. METHODS: A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (greater than= 15 N), velopharyngeal closure test (greater than= 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high-resolution manometry. RESULTS: Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P less than 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow-up [1.7 (0-3) vs 0.5 (0-2), P less than 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P less than 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P less than 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P less than 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). CONCLUSION: Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence.

  • 297.
    Hagman, H.
    et al.
    County Hospital Ryhov, Sweden.
    Frodin, J. -E.
    Karolinska University Hospital, Sweden.
    Berglund, A.
    University of Uppsala Hospital, Sweden.
    Sundberg, J.
    Skåne University Hospital, Sweden.
    Vestermark, L. W.
    Odense University Hospital, Denmark.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fernebro, E.
    Vaxjo Hospital, Sweden.
    Johnsson, A.
    Skåne University Hospital, Sweden.
    A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 1, p. 140-147Article in journal (Refereed)
    Abstract [en]

    Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.

  • 298.
    Hagopian, William
    et al.
    Pacific Northwest Diabet Research Institute, WA USA .
    Ferry, Robert J Jr.
    Le Bonheur Childrens Hospital, TN USA .
    Sherry, Nicole
    Massachusetts Gen Hospital, MA USA .
    Carlin, David
    MacroGenics, MD USA .
    Bonvini, Ezio
    MacroGenics, MD USA .
    Johnson, Syd
    MacroGenics, MD USA .
    Stein, Kathryn E.
    MacroGenics, MD USA .
    Koenig, Scott
    MacroGenics, MD USA .
    Daifotis, Anastasia G.
    MacroGenics, MD USA .
    Herold, Kevan C.
    Yale University, CT USA .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Teplizumab Preserves C-Peptide in Recent-Onset Type 1 Diabetes2013In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, no 11, p. 3901-3908Article in journal (Refereed)
    Abstract [en]

    Protege was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean area under the curve (AUC), a prespecified secondary end point, at 2 years versus placebo. In analyses of prespecified and post hoc subsets at entry, U.S. residents, patients with C-peptide mean AUC andgt;0.2 nmol/L, those randomized 6 weeks after diagnosis, HbA(1c) andlt;7.5% (58 mmol/mol), insulin use andlt;0.4 units/kg/day, and 8-17 years of age each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Antidrug antibodies developed in some patients, without apparent change in drug efficacy. No new safety or tolerability issues were observed during year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.

  • 299.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Behm, Pascal
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. University of Applied Sciences in Northwest Switzerland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence spectroscopy using indocyanine green for lymph node mapping2014In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, ISSN 0277-786X, Vol. 8935, no 893504, p. 1-6Article in journal (Refereed)
    Abstract [en]

    The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

  • 300.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Fluorescence spectroscopy and optical coherence tomography for brain tumor detection2016Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.

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