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  • 101.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    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.
    Tesselaar, Erik
    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 Radiation Physics.
    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.
    Farnebo, Simon
    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.
    Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 101, 20-25 p.Article in journal (Refereed)
    Abstract [en]

    Background: : Venous occlusion in the skin is difficult to detect by existing measurement techniques. Our aim was to find out whether Tissue Viability Imaging (TiVi) was better at detecting venous occlusion by comparing it with results of laser Doppler flowmetry (LDF) during graded arterial and venous stasis in human forearm skin. Methods: : Arterial and venous occlusions were simulated in 10 healthy volunteers by inflating a blood pressure cuff around the upper right arm. Changes in the concentration of red blood cells (RBC) were measured using TiVi, while skin perfusion and concentration of moving red blood cells (CMBC) were measured using static indices of LDF during exsanguination and subsequent arterial occlusion, postocclusive reactive hyperaemia, and graded increasing and decreasing venous stasis. Results: : During arterial occlusion there was a significant reduction in the mean concentration of RBC from baseline, as well as in perfusion and CMBC (p less than 0.008). Venous occlusion resulted in a significant 28% increase in the concentration of RBC (p = 0.002), but no significant change in perfusion (mean change -14%) while CMBC decreased significantly by 24% (p = 0.02). With stepwise increasing occlusion pressures there was a significant rise in the TiVi index and reduction in perfusion (p = 0.008), while the reverse was seen when venous flow was gradually restored. Conclusion: : The concentration of RBC measured with TiVi changes rapidly and consistently during both total and partial arterial and venous occlusions, while the changes in perfusion, measured by LDF, were less consistent This suggests that TiVi could be a more useful, non-invasive clinical monitoring tool for detecting venous stasis in the skin than LDF.

  • 102.
    Berglund, Caroline
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Ekströmer, Karin
    Department of Radiology, Mälarsjukhuset Eskilstuna Hospital, Sweden.
    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.
    Primary Chronic Osteomyelitis of the Jaws in Children: An Update on Pathophysiology, Radiological Findings, Treatment Strategies, and Prospective Analysis of Two Cases2015In: Case Reports in Dentistry, ISSN 2090-6447, E-ISSN 2090-6455, Vol. 2015, no 152717Article in journal (Refereed)
    Abstract [en]

    Objective. Primary chronic osteomyelitis (PCO) of the jaws in children is associated with pain, trismus, and swelling. In children, temporomandibular joint involvement is rare and few studies have been published due to the relatively low incidence. This paper presents two cases of mandibular PCO in children with the involvement of the collum mandibulae. In addition, a review of the literature regarding demographic data, histological, radiological, and laboratory findings, and treatment strategies of PCO was also performed. Material and Methods. Prospective analyses of two PCO cases. A PubMed search was used and the articles were sorted according to their corresponding key area of focus. Results. Review of the literature revealed twenty-four cases of PCO with two cases of mandibular condyle involvement. The mean age was 18 years; the male to female ratio was 1 : 3. Most of the patients were treated with anti-inflammatory drugs in combination with decortication. Clinical recurrence was seen in 7 cases. Conclusion. A combination of anti-inflammatory drugs and surgical intervention appears to be the first choice of treatment. However, surgical removal of necrotic tissue adjacent to collum mandibulae has its limitations in children. Further investigations are of utmost importance in order to increase our knowledge and understanding of this disease.

  • 103.
    Bergmark, Karin
    et al.
    Divisions of Gynecological Oncology and Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Division of Gynecological Oncology Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Dickman, Paul W
    Division of Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Henningsohn, Lars
    Division of Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Steineck, Gunar
    Division of Clinical Epidemiology, Department of Oncology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
    Vaginal changes and sexuality in women with a history of cervical cancer.1999In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 340, no 18, 1383-1389 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known.

    METHODS: In 1996 and 1997, we attempted to contact 332 women with a history of early-stage cervical cancer (age range, 26 to 80 years) who had been treated in 1991 and 1992 at the seven departments of gynecological oncology in Sweden and 489 women without a history of cancer (controls) to ask them to answer an anonymous questionnaire about vaginal changes and sexual function.

    RESULTS: We received completed questionnaires from 256 of the women with a history of cervical cancer and 350 of the controls. A total of 167 of 247 women with a history of cancer (68 percent) and 236 of 330 controls (72 percent) reported that they had regular vaginal intercourse. Twenty-six percent of the women who had cancer and 11 percent of the controls reported insufficient vaginal lubrication for sexual intercourse, 26 percent of the women who had cancer and 3 percent of the controls reported a short vagina, and 23 percent of the women who had cancer and 4 percent of the controls reported an insufficiently elastic vagina. Twenty-six percent of the women who had cancer reported moderate or much distress due to vaginal changes, as compared with 8 percent of the women in the control group. Dyspareunia was also more common among the women who had cervical cancer. The frequency of orgasms and orgasmic pleasure was similar in the two groups. Among the women who had cervical cancer, the type of treatment received had little if any effect on the prevalence of specific vaginal changes.

    CONCLUSIONS: Women who have been treated for cervical cancer have persistent vaginal changes that compromise sexual activity and result in considerable distress.

  • 104.
    Bergmark, Karin
    et al.
    Department of Oncology, Gynecological Oncology, Clinical Cancer Epidemiology, Karolinska Institutet PO Box 4402 S-102 68 Stockholm Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Oncology, Gynecological Oncology, Karolinska Institutet, Stockholm Sweden.
    Dickman, Paul W
    Department of Oncology, Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Henningsohn, Lars
    Department of Oncology, Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden / Department of Urology, Huddinge Hospital, Stockholm, Sweden.
    Steineck, Gunnar
    Department of Oncology, Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Patient-rating of distressful symptoms after treatment for early cervical cancer.2002In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 81, no 5, 443-450 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: More refined information on sources of symptom-induced distress in a patient population can improve the quality of pretreatment information, make follow-up visits more efficient and guide research priorities in the efforts to modify treatments.

    METHODS: In a population-based epidemiological study covering all of Sweden, data were collected 1996-97 by means of an anonymous postal questionnaire. We attempted to enroll all 332 patients with stage IB-IIA cervical cancer registered in 1991-92 at the seven departments of gynecological oncology in Sweden.

    RESULTS: A total of 256 cases (77%) completed the questionnaire. After surgery, alone or in combination with intracavitary radiotherapy, several symptoms related to sexual dysfunction are the primary sources of symptom-induced distress (reduced orgasm frequency: much distress 23% (surgery alone) and 23% (intracavitary radiotherapy and surgery), respectively, overall intercourse dysfunction: much distress 17% and 20%, respectively, followed by lymphedema (much distress 14% and 14%, respectively). Dyspareunia (much distress 24%) and defecation urgency (much distress 22%) are two leading causes of distress after surgery and external radiotherapy. After treatment with radiotherapy alone, loose stool and dyspareunia were the two most distressful symptoms (much distress 19% each). When a symptom occurs, fecal leakage and reduced orgasm frequency are the two most distressful ones (measured as much distress, 38% each).

    CONCLUSIONS: The observed symptoms are distressful and should, if one focuses on patient satisfaction, be given priority.

  • 105.
    Bergmark, Karin
    et al.
    Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden / Department of Oncology and Pathology, Division of Clinical Cancer Epidemiology , Karolinska Institutet , Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden.
    Dickman, Paul W
    Department of Oncology and Pathology, Division of Clinical Cancer Epidemiology, and Department of Medical Epidemiology and Biostatistics , Karolinska Institutet , Stockholm, Sweden.
    Steineck, Gunnar
    Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden / Department of Urology , Karolinska University Hospital , Huddinge, Sweden.
    Henningsohn, Lars
    Gynecological Oncology, Department of Oncology and Pathology Radiumhemmet , Karolinska Institutet , Stockholm, Sweden.
    Synergy between sexual abuse and cervical cancer in causing sexual dysfunction.2005In: Journal of sex & marital therapy, ISSN 0092-623X, E-ISSN 1521-0715, Vol. 31, no 5, 361-83 p.Article in journal (Refereed)
    Abstract [en]

    Experiencing a sexual abuse creates a life-long traumatic memory. The life-long effect of such abuse on sexuality, well-being, the risk of contracting cervical cancer, or problems after treatment for cervical cancer is not known. A population-based follow-up study in 1996-97 that used an anonymous postal questionnaire for data collection, 256 women with stage IB-IIA cervical cancer registered in 1991-92 in Sweden, and 350 women without cervical cancer frequency matched for age and region of residence, provided information. Among the women with a history of cervical cancer and the control women, 46 (18%) and 50 (15%), respectively, reported a history of sexual abuse. The follow-up was 1-70 years after the sexual abuse. The relative risk (with 95% confidence interval) of decreased well-being was 2.4 (1.1-5.2) among controls and 2.7 (1.1-6.4) among former cervical cancer patients. A history of both sexual abuse and cervical cancer gave a relative risk of 30.0 (7.0-129.0) for superficial dyspareunia. Sexual abuse increased the risk of sexual problems after treatment. The sexually abused cervical cancer patients were generally less willing than other patients to trade off possible maximal survival and forgo parts of the treatment. A history of sexual abuse and cervical cancer are both independent risk factors for sexual dysfunction and decreased well-being, and there may be a large synergy when both factors are combined. Diagnosis and treatment of cervical cancer may be improved by recognition of a sexual abuse history.

  • 106.
    Bergstrand, Sara
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Källman, Ulrika
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Department of Dermatology, Södra Älvsborgs Sjukhus, Borås, Sweden.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Lindberg, Lars-Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    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.
    Lindgren, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Pressure-induced vasodilation and reactive hyperemia at different depths in sacral tissue under clinically relevant conditions2014In: Microcirculation, ISSN 1073-9688, Vol. 21, no 8, 761-771 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To characterize pressure-induced vasodilatation and reactive hyperemia at different sacral tissue depths in different populations under clinically relevant pressure exposure.

    METHODS: Forty-two subjects (< 65 years), 38 subjects (≥ 65 years), and 35 patients (≥ 65 years) participated. Interface pressure, skin temperature, and blood flow at tissue depths of 1 mm, 2 mm, and 10 mm (using laser Doppler flowmetry and photoplethysmography) were measured in the sacral tissue before, during, and after load in a supine position.

    RESULTS: pressure-induced vasodilatation and reactive hyperemia were observed at three tissue depths. At 10 mm depth, the proportion of subjects with a lack of pressure-induced vasodilatation was higher compared to superficial depths. The patients had higher interface pressure during load than the healthy individuals, but there were no significant differences in blood flow. Twenty-nine subjects in all three study groups were identified with a lack of pressure-induced vasodilatation and reactive hyperemia.

    CONCLUSIONS: pressure-induced vasodilatation and reactive hyperemia can be measured at different tissue depths. A lack of these responses was found in healthy individuals as well as in patients indicating an innate susceptibility in some individuals, and are potential important factors to evaluate in order to better understand the etiology of pressure ulcers.

  • 107.
    Bergström, Malin
    et al.
    Stockholm University, Sweden.
    Fransson, Emma
    Stockholm University, Sweden.
    Modin, Bitte
    Stockholm University, Sweden.
    Berlin, Marie
    National Board Health and Welf, Sweden; Stockholm University, Sweden.
    Gustafsson, Per A.
    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.
    Hjern, Anders
    Stockholm University, Sweden; Karolinska Institute, Sweden.
    Fifty moves a year: is there an association between joint physical custody and psychosomatic problems in children?2015In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 69, no 8, 769-774 p.Article in journal (Refereed)
    Abstract [en]

    Background In many Western countries, an increasing number of children with separated parents have joint physical custody, that is, live equally much in their parents respective homes. In Sweden, joint physical custody is particularly common and concerns between 30% and 40% of the children with separated parents. It has been hypothesised that the frequent moves and lack of stability in parenting may be stressful for these children. Methods We used data from a national classroom survey of all sixth and ninth grade students in Sweden (N=147839) to investigate the association between childrens psychosomatic problems and living arrangements. Children in joint physical custody were compared with those living only or mostly with one parent and in nuclear families. We conducted sex-specific linear regression analyses for z-transformed sum scores of psychosomatic problems and adjusted for age, country of origin as well as childrens satisfaction with material resources and relationships to parents. Clustering by school was accounted for by using a two-level random intercept model. Results Children in joint physical custody suffered from less psychosomatic problems than those living mostly or only with one parent but reported more symptoms than those in nuclear families. Satisfaction with their material resources and parent-child relationships was associated with childrens psychosomatic health but could not explain the differences between children in the different living arrangements. Conclusions Children with non-cohabitant parents experience more psychosomatic problems than those in nuclear families. Those in joint physical custody do however report better psychosomatic health than children living mostly or only with one parent. Longitudinal studies with information on family factors before and after the separation are needed to inform policy of childrens postseparation living arrangements.

  • 108.
    Berhan, Yonas T.
    et al.
    Umeå University, Sweden.
    Mollsten, Anna
    Umeå University, Sweden.
    Carlsson, Annelie
    Lund University, Sweden.
    Högberg, Lotta
    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 Norrköping.
    Ivarsson, Anneli
    Umeå University, Sweden.
    Dahlquist, Gisela
    Umeå University, Sweden.
    Five-region study finds no evidence of undiagnosed type 2 diabetes in Swedish 11- to 13-year-olds2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 10, 1078-1082 p.Article in journal (Refereed)
    Abstract [en]

    AimChildhood obesity is now an established public health problem in most developed countries, and there is concern about a parallel increase of type 2 diabetes. The aim of this study was to estimate the prevalence of undiagnosed type 2 diabetes in overweight Swedish school children from 11 to 13years of age. MethodsBody mass index (BMI) was measured in 5528 schoolchildren in the 6th grade, from 11 to 13years of age, in five different regions in Sweden. Overweight was defined by international age- and sex-specific BMI cut-offs, corresponding to adult BMI cut-offs of 25kg/m(2) at 18years of age (ISO-BMI 25, n=1275). Haemoglobin A1c (HbA1c) was measured in 1126 children with ISO-BMI 25. Children with a Diabetes Control and Complications Trial aligned HbA1c 6.1% on two occasions underwent an oral glucose tolerance test (OGTT) to establish the diabetes diagnosis. ResultsOf 1126 children with ISO-BMI 25, 24 (2.1%) had at least one HbA1c value 6.1%. Three of them had HbA1c 6.1% on two occasions, and all of them had a normal OGTT. ConclusionIn this cross-sectional, population-based screening study of a high-risk group of 11- to 13-year-old Swedish school children, we found no indication of undiagnosed diabetes or impaired glucose tolerance.

  • 109.
    Berin, Emilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hammar, Mats
    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.
    Lindblom, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Lindh Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Spetz, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Resistance training for hot flushes in postmenopausal women: Randomized controlled trial protocol2016In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 85, 96-103 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: Hot flushes and night sweats affect 75% of all women after menopause and is a common reason for decreased quality of life in mid-aged women. Hormone therapy is effective in ameliorating symptoms but cannot be used by all women due to contraindications and side effects. Engagement in regular exercise is associated with fewer hot flushes in observational studies, but aerobic exercise has not proven effective in randomized controlled trials. It remains to be determined whether resistance training is effective in reducing hot flushes and improves quality of life in symptomatic postmenopausal women. The aim of this study is to investigate the effect of standardized resistance training on hot flushes and other health parameters in postmenopausal women. Study design: This is an open, parallel-group, randomized controlled intervention study conducted in Linkoping, Sweden. Sixty symptomatic and sedentary postmenopausal women with a mean of at least four moderate to severe hot flushes per day or 28 per week will be randomized to an exercise intervention or unchanged physical activity (control group). The intervention consists of 15 weeks of standardized resistance training performed three times a week under supervision of a physiotherapist. Main outcome measures: The primary outcome is hot flush frequency assessed by self-reported hot flush diaries, and the difference in change from baseline to week 15 will be compared between the intervention group and the control group. Conclusion: The intention is that this trial will contribute to the evidence base regarding effective treatment for hot flushes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 110. Berin, Emilia
    et al.
    Sundell, micaela
    Karki, Chanda
    Department of Obstetrics and Gynecology, Kathmandu Medical College, Kathmandu, Nepal.
    Brynhildsen, Jan
    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.
    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.
    Contraceptive knowledge and attitudes among women seeking induced abortion in Kathmandu, Nepal2014In: International Journal of Women's Health, ISSN 1179-1411, Vol. 6, no 1, 335-341 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To map the knowledge about and attitudes toward birth control methods among women in Kathmandu, Nepal, and to compare the results between women seeking an induced abortion and a control group. Method: This was a cross-sectional cohort study with matched controls. Women aged 15-49 years seeking medical care at the Department of Gynecology and Obstetrics at Kathmandu Medical College were included and interviewed. A case was defined as a woman who sought an elective medical or surgical abortion. A control was defined as a woman who sought medical care at the outpatient department or had already been admitted to the ward for reasons other than elective abortion. A questionnaire developed for the study - dealing with different demographic characteristics as well as knowledge about and attitudes toward contraceptives - was filled out based on the interview. Results: A total of 153 women were included: 64 women seeking an abortion and 89 controls. Women seeking an abortion had been pregnant more times than the control group and were more likely to have been informed about contraceptives. Women with higher education were less likely to seek an abortion than women with lower education. There was no significant difference in knowledge about and attitudes toward contraceptives between cases and controls. The women considered highest possible effectiveness to be the most important feature when deciding on a birth control method. Conclusion: Women seeking abortion in Kathmandu had shorter education and a history of more pregnancies and deliveries than women in the control group. Education and counseling on sex and reproduction as well as on contraceptive methods probably need to be improved in Nepal to avoid unwanted pregnancies. Attitudes about contraceptives need to be further investigated to develop better and more effective methods to educate women about family planning in order to increase reproductive health. © 2014 Berin et al.

  • 111.
    Berkius, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Anaesthesia and Intensive Care, Västervik County Hospital, Västervik, Sweden.
    Engerström, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Orwelius, Lotti
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping,.
    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.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Walther, Sten M
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, R211- p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Mortality amongst COPD patients treated on the ICU is high. Health-related quality of life (HRQL) after intensive care is a relevant concern for COPD patients, their families and providers of health care. Still, there are few HRQL studies after intensive care of this patient group. Our hypothesis was that HRQL of COPD patients treated on the ICU declines rapidly with time.

    METHODS: Fifty-one COPD patients (COPD-ICU group) with an ICU stay longer than 24 hours received a questionnaire at 6, 12 and 24 months after discharge from ICU. HRQL was measured using two generic instruments: the EuroQoL instrument (EQ-5D and EQ-VAS) and the Short Form 36 Health Survey (SF-36). The results were compared to HRQL of two reference groups from the general population; an age- and sex-adjusted reference population (Non-COPD reference) and a reference group with COPD (COPD reference).

    RESULTS: HRQL of the COPD-ICU group at 6 months after discharge from ICU was lower compared to the COPD reference group: Median EQ-5D was 0.66 vs. 0.73, P=0.08 and median EQ-VAS was 50 vs.55, P<0.05. There were no significant differences in the SF-36 dimensions between the COPD-ICU and COPD-reference groups, although the difference in physical functioning (PF) approached statistical significance (P=0.059). Patients in the COPD-ICU group who were lost to follow-up after 6 months had low HRQL scores at 6 months. Scores for patients who died were generally lower compared to patients who failed to respond to the questionnaire. The PF and social functioning (SF) scores in those who died were significantly lower compared to patients with a complete follow up. HRQL of patients in the COPD-ICU group that survived a complete 24 months follow up was low but stable with no statistically significant decline from 6 to 24 months after ICU discharge. Their HRQL at 24 months was not significantly different from HRQL in the COPD reference group.

    CONCLUSIONS: HRQL in COPD survivors after intensive care was low but did not decline from 6 to 24 months after discharge from ICU. Furthermore, HRQL at 24 months was similar to patients with COPD who had not received ICU treatment.

  • 112.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Anti-RANKL treatment improves screw fixation in cancellous bone in rats2015In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 46, no 6, 990-995 p.Article in journal (Refereed)
    Abstract [en]

    Bisphosphonates improve implant fixation in randomised clinical trials of knee prostheses, hip prostheses and dental implants. However, a limited amount of bone resorption is required for bisphosphonates to exert an effect. Anti-RANKL treatment does not have this limitation, and we therefore tested whether if they might be more effective for improvement of implant fixation. This is of interest, as anti-RANKL treatment with denosumab is now in common clinical use. Male SD rats received a stain-less steel screw in the right proximal tibia and a drill hole in the left (n = 42). They were randomised to subcutaneous injections of either alendronate (20 mu g/kg/day), alendronate (200 mu g/kg/day), osteoprotegerin with an Fc tag (OPG-Fc; 8 mg/kg, twice weekly), or saline control. After 4 weeks, the fixation of the steel screw was measured by pull-out test. The tibia with the drill hole was evaluated with mu CT. OPG-Fc increased the pull-out force compared to saline controls by 153% (p less than 0.001). There was no significant difference between OPG-Fc and the alendronate groups. OPG-Fc increased the bone density (BV/TV) in the previous drill hole compared to controls 7-fold (p less than 0.001). This increase was higher than with any alendronate dose (p less than 0.001). OPG-Fc increased the bone density of the L5 vertebral body, but there was no significant difference between OPG-Fc and alendronate. Our results suggest that screw fixation in cancellous bone can be dramatically improved by an antiRANKL agent. The effect was comparable to very high bisphosphonate doses. Screw insertion in cancellous bone elicits a metaphyseal fracture healing response, and our findings might be relevant not only for implant fixation, but also for fracture healing in cancellous bone.

  • 113.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 6, 745-750 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods - Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results - The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation - The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model.

  • 114.
    Bill-Axelson, Anna
    et al.
    University of Uppsala Hospital, Sweden .
    Holmberg, Lars
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Garmo, Hans
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Rider, Jennifer R.
    Brigham and Womens Hospital, MA USA Harvard University, MA USA Harvard University, MA 02115 USA .
    Taari, Kimmo
    University of Helsinki, Finland .
    Busch, Christer
    University of Uppsala Hospital, Sweden .
    Nordling, Stig
    University of Helsinki, Finland .
    Haggman, Michael
    University of Uppsala Hospital, Sweden .
    Andersson, Swen-Olof
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Spångberg, Anders
    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.
    Andren, Ove
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Palmgren, Juni
    Karolinska Institute, Sweden .
    Steineck, Gunnar
    Karolinska Institute, Sweden Sahlgrens Acad, Sweden .
    Adami, Hans-Olov
    Karolinska Institute, Sweden Harvard University, MA 02115 USA .
    Johansson, Jan-Erik
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, 932-942 p.Article in journal (Refereed)
    Abstract [en]

    BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 115.
    Birch Tyrberg, Rasmus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Kjölhede, Preben
    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.
    Deliveries among teenage women - with emphasis on incidence and mode of delivery: a Swedish national survey from 1973 to 20102013In: BMC Pregnancy and Childbirth, ISSN 1471-2393, Vol. 13, no 204Article in journal (Refereed)
    Abstract [en]

    Background: Since the 1970-ies Sweden has actively developed strategies in social care, education and health care in order to counteract the negative consequences of adolescent parenthood. The aims of this study are to determine the annual incidence of singleton delivery among adolescents 1973-2010 and analyse obstetric and neonatal outcomes. Methods: A retrospective cohort study, using data from the Swedish Medical Birth Register was conducted. All singleton deliveries in Sweden between 1973 and 2010 were included. Totally 1,941,940 women had 3,761,576 deliveries during the period. Analyses of obstetric and neonatal outcome were restricted to 1992-2010. Adolescents were subdivided into three groups: less than16 years (n = 472), 16-17 years (n = 5376), 18-19 years (n = 23560). The reference group consisted of women age 20-30 years (n = 893505). Data were analysed using multivariate logistic regression models adjusted for confounding factors and presented as crude and adjusted odds ratios with 95% confidence interval. Results: The annual incidence of teenage births decreased significantly from 7.7 to 1.6%. Teenagers were more likely to deliver normally vaginally (aOR 1.70 (95% CI 1.64-1.75), less likely to have Caesarean section (aOR 0.61 (95% CI 0.58-0.64), and had a greater risk of delivering prematurely (less than 28 weeks)(aOR 1.61 (95% CI 1.31-2.00), but did not have more small-for-gestational-age babies (aOR 1.07 (95% CI 0.99-1.14). Risks of placenta previa, postpartum haemorrhage greater than 1000 ml and perineal rupture were significantly lower among teenagers. Although the rate with Apgar score less than 7 at 5 minutes was similar the teenagers neonates showed less fetal distress and meconium aspiration. Conclusion: Adolescent births have steadily decreased in Sweden. Adolescents were more likely to be delivered vaginally than the adult women. The risks for obstetric maternal complications for adolescents were lower than for adult women except for the risk of prematurity.

  • 116.
    Bjohle, J
    et al.
    Karolinska Institute, Sweden .
    Bergqvist, J
    Karolinska Institute, Sweden .
    Gronowitz, J S.
    Biov Int AB, Sweden .
    Johansson, H
    Karolinska Institute, Sweden .
    Carlsson, L
    Sundsvall Gen Hospital, Sweden .
    Einbeigi, Z
    Sahlgrens University Hospital, Sweden .
    Linderholm, B
    Sahlgrens University Hospital, Sweden .
    Loman, N
    Lund University, Sweden .
    Malmberg, M
    Helsingborg Gen Hospital, Sweden .
    Soderberg, M
    Lund University, Sweden .
    Sundquist, M
    Kalmar Gen Hospital, Sweden .
    Walz, Thomas
    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. Karolinska Institute, Sweden .
    Ferno, M
    Lund University, Sweden .
    Bergh, J
    Karolinska Institute, Sweden .
    Hatschek, T
    Karolinska Institute, Sweden .
    Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial2013In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 139, no 3, 751-758 p.Article in journal (Refereed)
    Abstract [en]

    The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.

  • 117.
    Björnsson, Bergthor
    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.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Hans
    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.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, 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 Surgery in Linköping.
    Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 6, 1775-1783 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

    METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

    RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

    CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

  • 118.
    Björnsson, Bergthor
    et al.
    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.
    Kullman, Eric
    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.
    Gasslander, Thomas
    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.
    Sandström, Per
    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.
    Early endoscopic treatment of blunt traumatic pancreatic injury2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 12, 1435-1443 p.Article, review/survey (Refereed)
    Abstract [en]

    Blunt pancreatic trauma is a rare and challenging situation. In many cases, there are other associated injuries that mandate urgent operative treatment. Morbidity and mortality rates are high and complications after acute pancreatic resections are common. The diagnosis of pancreatic injuries can be difficult and often requires multimodal approach including Computed Tomography scans, Magnetic resonance imaging and Endoscopic retrograde cholangiopancreaticography (ERCP). The objective of this paper is to review the application of endoprothesis in the settings of pancreatic injury. A review of the English literature available was conducted and the experience of our centre described. While the classical recommended treatment of Grade III pancreatic injury (transection of the gland and the pancreatic duct in the body/tail) is surgical resection this approach carries high morbidity. ERCP was first reported as a diagnostic tool in the settings of pancreatic injury but has in recent years been used increasingly as a treatment option with promising results. This article reviews the literature on ERCP as treatment option for pancreatic injury and adds further to the limited number of cases reported that have been treated early after the trauma.

  • 119.
    Björnsson, Bergthor
    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.
    Lundgren, L
    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.
    A Personal Computer Freeware as a Tool for Surgeons to Plan Liver Resections.2016In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 3, 153-157 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: The increase in liver surgery and the proportion of resections done on the margin to postoperative liver failure make preoperative calculations regarding liver volume important. Earlier studies have shown good correlation between calculations done with ImageJ and specimen weight as well as volume calculations done with more robust systems. The correlation to actual volumes of resected liver tissue has not been investigated, and this was the aim of this study.

    MATERIAL AND METHODS: A total of 30 patients undergoing well-defined liver resections were included in this study. Volumes calculated with ImageJ were compared to volume measurements done after the retrieval of resected liver tissue.

    RESULTS AND CONCLUSIONS: A strong correlation between calculated and measured liver volume was found with sample concordance correlation coefficient (ρc) = 0.9950. The knowledge on the nature of liver resections sets liver surgeons in a unique position to be able to accurately predict the volumes to be resected and, therefore, also the volume that will remain after surgery. This becomes increasingly important with the evolvement of methods to extend the boundaries of liver surgery. ImageJ is a reliable tool to preoperatively assess liver volume.

  • 120.
    Björnsson, Bergthor
    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 Linköping.
    Sandström, Per
    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.
    Laparoscopic distal pancreatectomy for adenocarcinoma of the pancreas2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 37, 13402-13411 p.Article in journal (Refereed)
    Abstract [en]

    Since the first report on laparoscopic distal pancreatectomy (LDP) appeared in the 1990s, the procedure has been performed increasingly frequently to treat both benign and malignant lesions of the pancreas. Many earlier publications have shown LDP to be a good alternative to open distal pancreatectomy for benign lesions, although this has never been studied in a prospective, randomized manner. The evidence for the use of LDP to treat adenocarcinoma of the pancreas is not as well established. The purpose of this review is to evaluate the current evidence for LDP in cases of pancreatic adenocarcinoma. We conducted a review of English language publications reporting LDP results between 1990 and 2013. All studies reporting results in patients with histologically proven pancreatic adenocarcinoma were included. Thirty-nine publications were found and included in the results for a total of 309 cases of pancreatic adenocarcinoma (potential double publications were not eliminated). Most LDP procedures are performed in selected cases and generally involve smaller tumors than open distal pancreatectomy (ODP) procedures. Some of the papers report unselected cases and include procedures on larger tumors. The number of lymph nodes harvested using LDP is comparable to the number obtained with ODP, as is the frequency of R0 resections. Current data suggest that similar short term oncological results can be obtained using LDP as those obtained using ODP.

  • 121.
    Björnsson, Bergthor
    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.
    Sparrelid, E.
    Karolinska Institute, Sweden.
    Hasselgren, Kristina
    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.
    Gasslander, Thomas
    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.
    Isaksson, B.
    Karolinska Institute, Sweden.
    Sandström, 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 Surgery in Linköping.
    Associating Liver Partition and Portal Vein Ligation for Primary Hepatobiliary Malignancies and Non-Colorectal Liver Metastases2016In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 3, 158-162 p.Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Associating liver partition and portal vein ligation for staged hepatectomy may increase the possibility of radical resection in the case of liver malignancy. Concerns have been raised about the high morbidity and mortality associated with the procedure, particularly when applied for diagnoses other than colorectal liver metastases. The aim of this study was to analyze the initial experience with associating liver partition and portal vein ligation for staged hepatectomy in cases of non-colorectal liver metastases and primary hepatobiliary malignancies in Scandinavia. Materials and Methods: A retrospective analysis of all associating liver partition and portal vein ligation for staged hepatectomy procedures performed at two Swedish university hospitals for non-colorectal liver metastases and primary hepatobiliary malignancies was performed. The primary focus was on the safety of the procedure. Results and Conclusion: Ten patients were included: four had hepatocellular cancer, three had intrahepatic cholangiocarcinoma, one had a Klatskin tumor, one had ocular melanoma metastasis, and one had a metastasis from a Wilms tumor. All patients completed both operations, and the highest grade of complication (according to the Clavien-Dindo classification) was 3A, which was observed in one patient. No 90-day mortality was observed. Radical resection (R0) was achieved in nine patients, while the resection was R2 in one patient. The low morbidity and mortality observed in this cohort compared with those of earlier reports on associating liver partition and portal vein ligation for staged hepatectomy for diagnoses other than colorectal liver metastases may be related to the selection of patients with limited comorbidity. In addition, procedures other than associating liver partition and portal vein ligation for staged hepatectomy had been avoided in most of the patients. In conclusion, associating liver partition and portal vein ligation for staged hepatectomy can be applied to primary hepatobiliary malignancies and non-colorectal liver metastases with acceptable rates of morbidity and mortality.

  • 122.
    Björnsson, Bergthor
    et al.
    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.
    Sparrelid, E.
    Karolinska Institute, Sweden.
    Rosok, B.
    Oslo University Hospital, Norway.
    Pomianowska, E.
    Oslo University Hospital, Norway.
    Hasselgren, Kristina
    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.
    Gasslander, Thomas
    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.
    Bjornbeth, B. A.
    Oslo University Hospital, Norway.
    Isaksson, B.
    Karolinska Institute, Sweden.
    Sandström, Per
    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.
    Associating liver partition and portal vein ligation for staged hepatectomy in patients with colorectal liver metastases - Intermediate oncological results2016In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 4, 531-537 p.Article in journal (Refereed)
    Abstract [en]

    Background: Colorectal liver metastases (CRLM) not amenable for resection have grave prognosis. One limiting factor for surgery is a small future liver remnant (FLR). Early data suggests that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively increases the volume of the FLR allowing for resection in a larger fraction of patients than conventional two-stage hepatectomy (TSH) with portal vein occlusion (PVO). Oncological results of the treatment are lacking. The aim of this study was to assess the intermediate oncological outcomes after ALPPS in patients with CRLM. Material and methods: Retrospective analysis of all patients with CRLM operated with ALPPS at the participating centres between December 2012 and May 2014. Results: Twenty-three patients (16 male, 7 female), age 67 years (28-80) were operated for 6.5 (1-38) metastases of which the largest was 40 nun (14-130). Six (27.3%) patients had extra-hepatic metastases, 16 (72.7%) synchronous presentation. All patients received chemotherapy, 6 cycles (3-25) preoperatively and 16 (70%) postoperatively. Ten patients (43%) were rescue ALPPS after failed PVO. Severe complications occurred in 13.6% and one (4.5%) patient died within 90 days of surgery. After a median follow-up of 22.5 months from surgery and 33.5 months from diagnosis of liver metastases estimated 2 year overall survival was 59% (from surgery) and 73% (from diagnosis). Liver only recurrences (n = 8), were treated with reresection/ablation (n = 7) while lung recurrences were treated with chemotherapy. Conclusion: The overall survival, rate of severe complications and perioperative mortality associated with ALPPS for patients with CRLM is comparable to TSH. (C) 2016 Elsevier Ltd. All rights reserved.

  • 123.
    Björnsson, Bergthor
    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 Linköping.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    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.
    Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 28, 9506-9512 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

  • 124.
    Björnsson Hallgren, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Holmgren, Theresa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Johansson, Kajsa
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Adolfsson, Lars
    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.
    A specific exercise strategy reduced the need for surgery in subacromial pain patients2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 19, 1431-1436 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up. The purposes of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score, rotator cuff status and radiological findings influenced the outcome. Patients and methods 97 patients on the waiting list for arthroscopic subacromial decompression had been randomised to a specific exercise programme or unspecific exercises (controls). After 3 months of exercises, the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up. 1 year after inclusion or 1 year after surgery, the number of patients who decided to have surgery in each group was compared. The choice of surgery was related to the baseline Constant-Murley score, ultrasound and radiographs taken at inclusion. Results All patients had improved significantly (pless than0.0001) in the Constant-Murley score at the 1-year follow-up. Significantly more patients in the control group decided to have surgery (63%) than those in the specific exercise group (24%; pless than0.0001). Patients who decided to have surgery had a significantly lower baseline Constant-Murley score and more often a full-thickness tear. Patients with partial tears did not differ from those with intact tendons. Interpretation The positive short-term results of specific exercises were maintained after 1 year, and this exercise strategy reduces the need for surgery. Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome.

  • 125.
    Björnström-Karlsson, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Turina, Dean
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Strid, Tobias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase C-epsilon-Dependent Mechanism in Neurons2014In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 5, e0097129- p.Article in journal (Refereed)
    Abstract [en]

    Background: The intravenous anaesthetic propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons. Orexin A (OA) is an endogenous neuropeptide regulating wakefulness and may counterbalance anaesthesia. We aim to investigate if OA interacts with anaesthetics by inhibition of the propofol-induced neurite retraction. Methods: In primary cortical cell cultures from newborn rats brains, live cell light microscopy was used to measure neurite retraction after propofol (2 mu M) treatment with or without OA (10 nM) application. The intracellular signalling involved was tested using a protein kinase C (PKC) activator [phorbol 12-myristate 13-acetate (PMA)] and inhibitors of Rho-kinase (HA-1077), phospholipase D (PLD) [5-fluoro-2-indolyl des-chlorohalopemide (FIPI)], PKC (staurosporine), and a PKC epsilon translocation inhibitor peptide. Changes in PKC epsilon Ser(729) phosphorylation were detected with Western blot. Results: The neurite retraction induced by propofol is blocked by Rho-kinase and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, staurosporine and PKC epsilon translocation inhibitor peptide. OA increases via PLD and propofol decreases PKC epsilon Ser(729) phosphorylation, a crucial step in the activation of PKC epsilon. Conclusions: Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC inhibits neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKC epsilon-mediated pathway, and PKC epsilon maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge.

  • 126.
    Bladh, Marie
    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.
    Birth Characteristics’ Impacton Future Reproduction and Morbidity Among Twins an dSingletons2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Globally, in both developed and developing countries, the twinning rates have increased since the early 70’s. A large proportion of twins are born preterm and/or small-for-gestational-age (SGA) and/or with a low birth weight. Several studies have been performed on the long-term effect of these non-optimal birth characteristics on future reproductive performance and morbidity. Yet, most studies exclude twins or higher order pregnancies and thus the findings are based on singleton pregnancies only.

    The aim of the present thesis was therefore to investigate the impact of non-optimal birth characteristics in terms of preterm birth, small-for-gestational age, and low birth weight, on the reproductive pattern and morbidity among twins and singletons Furthermore, the present thesis attempted to establish whether twins and singletons were affected in the same manner.

    The studies included in this thesis are prospective population-based register studies, including all men and women, alive and living in Sweden at age 13, who were born between 1973 and 1983 (1,000,037 singletons and 16,561 twins) for the first three studies with follow-up till the end of 2006 and 2009. The last study included all men and women, alive and living in Sweden at age 13, who were born between 1973 and 1993 (2,051,479 singletons and 39,726 twins) with follow-up till the end of 2012.

    In general, twins were found less likely to reproduce between 13 and 33 years of age compared with singletons. Stratifying data by different birth characteristics, it was found that twins had a lower likelihood of reproducing on several different birth characteristics (appropriate-for-gestational-age, normal birth weight, low birth weight, term birth, preterm birth). However, twins born very preterm had an increased likelihood of reproducing compared with singletons born very preterm.

    Not taking birth characteristics into account, twinning was associated with a higher degree of hospitalization. However, accounting for the diverging birth characteristics this difference diminished and for some diagnoses the relationship was reversed such that twins were actually less likely to be hospitalized compared with singletons.

    In terms of the heritability of non-optimal birth characteristics singleton mothers born preterm were more predisposed to give birth to a child that was preterm while singleton mothers born SGA more often gave birth to a child either born preterm or SGA. Among twins this heritability was not as evident. The only difference observed was among twin mothers born SGA who were more likely to give birth to a child born SGA.

    In the extended cohort comprising those born between 1973 and 1993, male and female twins were found to be less likely to become parents compared with singletons. No difference was found among women in terms of having a second child, while male twins were more likely to have a second child compared with male singletons. It was also found that the likelihood of becoming a first-time parent and second-time parent was positively associated with the number of siblings.

  • 127.
    Bladh, Marie
    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 of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    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.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Finnström, Orvar
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sydsjö, Gunilla
    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.
    Intergenerational cohort study of preterm and small-for-gestational-age birth in twins and singletons2015In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 18, no 5, 581-590 p.Article in journal (Refereed)
    Abstract [en]

    To date several studies have investigated the intergenerational effect of preterm and small-for-gestational-age births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and small for gestational age (SGA) among twins and singletons.

    A prospective population based register study of mother-first-born offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4073 twins and 264,794 singletons born in 1973-1983 and their firstborns born in 1986-2009. Preterm birth was defined as birth <37 weeks of gestation and SGA as < 2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers and mother’s socio-demographic factors in addition to maternal birth- characteristics.

    Among mothers born as singletons, being born preterm was associated with an increased risk for delivering a preterm child (adjusted OR 1.39, 95% CI 1.29-1.50) while being born SGA increased the likelihood of a SGA child (adjusted OR 3.04, 95% CI 2.80-3.30) as well as a preterm child (adjusted OR 1.30, 95% CI 1.20-1.40). In twin mothers, the corresponding ORs tended to be lower and the only statistically significant association was between a SGA mother and a SGA child (adjusted OR 2.15, 95% CI 1.40-3.31). A statistically significant interaction between twinning and mother’s size for gestational was identified in a multivariate linear regression analysis indicating that singleton mothers born SGA were associated with a lower birth weight compared to mothers not born SGA.

    Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons.

  • 128.
    Bladh, Marie
    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 of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    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.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Finnström, Orvar
    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.
    Sydsjö, Gunilla
    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.
    Reproductive pattern among twins and singletons in relation to number of siblings: a Swedish cohort study of individuals born between 1973 and 19932015Manuscript (preprint) (Other academic)
    Abstract [en]

    Background Twinning has been shown to be associated with a reduced reproductive rate compared to singletons. This can partly be explained by the birth-characteristics pertaining to twinning as many twins are born preterm, with low birth weight or small for gestational age. However, the intergenerational reproductive rate may also be due to familial factors such as number of siblings.

    Methods This is a register-based study of all men and women born in Sweden between 1973 and 1993 who were living in Sweden at 13 years of age. Data on the study objects’ own births as well as their offspring, parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios for the likelihood of becoming a parent were estimated using Cox’s proportion hazard models. All models were adjusted for socio-demographic and birth characteristics.

    Results Adjusting for number of siblings, socio-demographic factors and birth characteristics, twinning was associated with a decreased likelihood of becoming a first-time parent, compared with singletons both for females (HR (95% CI)=0.90 (0.88-0.93) and males (HR (95% CI)=0.96 (0.93-0.99). Having 3 or more siblings increased the chance of becoming a first-time parent among both male twins (HR (95% CI)=1.17 (1.08-1.27)) and singletons (HR (95% CI)=1.16 (1.15-1.18)) compared to having fewer than 3 siblings. This increased likelihood of becoming a parent was also present among female twins (HR (95% CI)=1.18 (1.10-1.26)) and singletons (HR (95% CI)=1.22 (1.21-1.24)).

    Conclusions Twins have a decreased likelihood of becoming a parent compared to singletons even when adjusting for number of siblings.

  • 129.
    Blanco, Ignacio
    et al.
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Kuchenbaecker, Karoline
    University of Cambridge, England.
    Cuadras, Daniel
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Wang, Xianshu
    Mayo Clin, MN USA.
    Barrowdale, Daniel
    University of Cambridge, England.
    Ruiz de Garibay, Gorka
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Librado, Pablo
    University of Barcelona, Spain.
    Sanchez-Gracia, Alejandro
    University of Barcelona, Spain.
    Rozas, Julio
    University of Barcelona, Spain.
    Bonifaci, Nuria
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    McGuffog, Lesley
    University of Cambridge, England.
    Pankratz, Vernon S.
    Mayo Clin, MN USA.
    Islam, Abul
    University of Dhaka, Bangladesh.
    Mateo, Francesca
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Berenguer, Antoni
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Petit, Anna
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Catala, Isabel
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Brunet, Joan
    Hospital Josep Trueta, Spain.
    Feliubadalo, Lidia
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Tornero, Eva
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Benitez, Javier
    Spanish National Cancer Centre CNIO, Spain; Biomed Network Rare Disease, Spain.
    Osorio, Ana
    Spanish National Cancer Centre CNIO, Spain; Biomed Network Rare Disease, Spain.
    Cajal, Teresa Ramon Y.
    Hospital Santa Creu and Sant Pau, Spain.
    Nevanlinna, Heli
    University of Helsinki, Finland; University of Helsinki, Finland.
    Aittomaki, Kristiina
    University of Helsinki, Finland.
    Arun, Banu K.
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Toland, Amanda E.
    Ohio State University, OH 43210 USA.
    Karlan, Beth Y.
    Cedars Sinai Medical Centre, CA 90048 USA.
    Walsh, Christine
    Cedars Sinai Medical Centre, CA 90048 USA.
    Lester, Jenny
    Cedars Sinai Medical Centre, CA 90048 USA.
    Greene, Mark H.
    National Cancer Institute, MD USA.
    Mai, Phuong L.
    National Cancer Institute, MD USA.
    Nussbaum, Robert L.
    University of Calif San Francisco, CA 94143 USA.
    Andrulis, Irene L.
    University of Toronto, Canada; University of Toronto, Canada; University of Toronto, Canada.
    Domchek, Susan M.
    University of Penn, PA 19104 USA; University of Penn, PA 19104 USA.
    Nathanson, Katherine L.
    University of Penn, PA 19104 USA; University of Penn, PA 19104 USA.
    Rebbeck, Timothy R.
    University of Penn Perelman, PA 19104 USA; University of Penn Perelman, PA 19104 USA.
    Barkardottir, Rosa B.
    University of Iceland, Iceland; University of Iceland, Iceland.
    Jakubowska, Anna
    Pomeranian Medical University, Poland.
    Lubinski, Jan
    Pomeranian Medical University, Poland.
    Durda, Katarzyna
    Pomeranian Medical University, Poland.
    Jaworska-Bieniek, Katarzyna
    Pomeranian Medical University, Poland.
    Claes, Kathleen
    University of Ghent, Belgium.
    Van Maerken, Tom
    University of Ghent, Belgium.
    Diez, Orland
    Vall Hebron Research Institute VHIR, Spain; University of Autonoma Barcelona, Spain.
    Hansen, Thomas V.
    Copenhagen University Hospital, Denmark.
    Jonson, Lars
    Copenhagen University Hospital, Denmark.
    Gerdes, Anne-Marie
    Copenhagen University Hospital, Denmark.
    Ejlertsen, Bent
    Copenhagen University Hospital, Denmark.
    de la Hoya, Miguel
    San Carlos Research Institute IdISSC, Spain.
    Caldes, Trinidad
    San Carlos Research Institute IdISSC, Spain.
    Dunning, Alison M.
    University of Cambridge, England.
    Oliver, Clare
    University of Cambridge, England.
    Fineberg, Elena
    University of Cambridge, England.
    Cook, Margaret
    University of Cambridge, England.
    Peock, Susan
    University of Cambridge, England.
    McCann, Emma
    Glan Clwyd Gen Hospital, Wales.
    Murray, Alex
    Singleton Hospital, Wales.
    Jacobs, Chris
    Guys and St Thomas National Health Serv NHS Fdn Trust, England.
    Pichert, Gabriella
    Guys and St Thomas National Health Serv NHS Fdn Trust, England.
    Lalloo, Fiona
    Central Manchester University Hospital National Health Serv NHS Fdn, England.
    Chu, Carol
    Yorkshire Regional Genet Serv, England.
    Dorkins, Huw
    Kennedy Galton Centre, England.
    Paterson, Joan
    Addenbrookes Hospital, England.
    Ong, Kai-Ren
    Birmingham Womens Hospital Healthcare National Health Serv, England.
    Teixeira, Manuel R.
    University of Porto, Portugal; University of Porto, Portugal.
    Teixeira,
    Netherlands Cancer Institute, The Netherlands.
    Hogervorst, Frans B. L.
    Netherlands Cancer Institute, The Netherlands.
    van der Hout, Annemarie H.
    University of Groningen, Netherlands.
    Seynaeve, Caroline
    Erasmus University, Netherlands.
    van der Luijt, Rob B.
    University of Medical Centre Utrecht, Netherlands.
    Ligtenberg, Marjolijn J. L.
    Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands; Leiden University, Netherlands.
    Devilee, Peter
    Leiden University, Netherlands; Leiden University, Netherlands.
    Wijnen, Juul T.
    Leiden University, Netherlands; Leiden University, Netherlands.
    Rookus, Matti A.
    Netherlands Cancer Institute, Netherlands.
    Meijers-Heijboer, Hanne E. J.
    Vrije University of VJ University of Medical Centre, Netherlands.
    Blok, Marinus J.
    Maastricht University, Netherlands.
    van den Ouweland, Ans M. W.
    Erasmus University, Netherlands.
    Aalfs, Cora M.
    University of Amsterdam, Netherlands.
    Rodriguez, Gustavo C.
    University of Chicago, IL 60637 USA.
    Phillips, Kelly-Anne A.
    Peter MacCallum Cancer Centre, Australia.
    Piedmonte, Marion
    Roswell Pk Cancer Institute, NY 14263 USA.
    Nerenstone, Stacy R.
    Hartford Hospital, CT USA.
    Bae-Jump, Victoria L.
    University of N Carolina, NC USA.
    OMalley, David M.
    Ohio State University, OH USA.
    Ratner, Elena S.
    Yale University, CT USA.
    Schmutzler, Rita K.
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Wappenschmidt, Barbara
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Rhiem, Kerstin
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Engel, Christoph
    University of Leipzig, Germany.
    Meindl, Alfons
    Technical University of Munich, Germany.
    Ditsch, Nina
    University of Munich, Germany.
    Arnold, Norbert
    University of Kiel, Germany.
    Plendl, Hansjoerg J.
    University of Kiel, Germany.
    Niederacher, Dieter
    University of Dusseldorf, Germany.
    Sutter, Christian
    University of Heidelberg Hospital, Germany.
    Wang-Gohrke, Shan
    University Hospital Ulm, Germany.
    Steinemann, Doris
    Hannover Medical Sch, Germany.
    Preisler-Adams, Sabine
    University of Munster, Germany.
    Kast, Karin
    Technical University of Dresden, Germany.
    Varon-Mateeva, Raymonda
    Charite, Germany.
    Gehrig, Andrea
    University of Wurzburg, Germany.
    Bojesen, Anders
    Vejle Hospital, Denmark.
    Sokilde Pedersen, Inge
    Aalborg University Hospital, Denmark.
    Sunde, Lone
    Aarhus University Hospital, Denmark.
    Birk Jensen, Uffe
    Aarhus University Hospital, Denmark.
    Thomassen, Mads
    Odense University Hospital, Denmark.
    Kruse, Torben A.
    Odense University Hospital, Denmark.
    Foretova, Lenka
    Masaryk Mem Cancer Institute, Czech Republic.
    Peterlongo, Paolo
    Fdn Italiana Ric Cancro, Italy.
    Bernard, Loris
    Cogentech Cancer Genet Test Lab, Italy.
    Peissel, Bernard
    Fdn Ist Nazl Tumori INT, Italy.
    Scuvera, Giulietta
    Fdn Ist Nazl Tumori INT, Italy.
    Manoukian, Siranoush
    Fdn Ist Nazl Tumori INT, Italy.
    Radice, Paolo
    Fdn Ist Nazl Tumori INT, Italy.
    Ottini, Laura
    University of Roma La Sapienza, Italy.
    Montagna, Marco
    IRCCS, Italy.
    Agata, Simona
    IRCCS, Italy.
    Maugard, Christine
    Hop University of Strasbourg, France.
    Simard, Jacques
    Centre Hospital University of Quebec, Canada; University of Laval, Canada.
    Soucy, Penny
    Centre Hospital University of Quebec, Canada; University of Laval, Canada.
    Berger, Andreas
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Fink-Retter, Anneliese
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Singer, Christian F.
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Rappaport, Christine
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Geschwantler-Kaulich, Daphne
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Tea, Muy-Kheng
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Pfeiler, Georg
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    John, Esther M.
    Cancer Prevent Institute Calif, CA USA.
    Miron, Alex
    Dana Farber Cancer Institute, MA 02115 USA.
    Neuhausen, Susan L.
    Beckman Research Institute City Hope, CA USA.
    Beth Terry, Mary
    Columbia University, NY USA.
    Chung, Wendy K.
    Columbia University, NY USA.
    Daly, Mary B.
    Fox Chase Cancer Centre, PA 19111 USA.
    Goldgar, David E.
    University of Utah, UT USA.
    Janavicius, Ramunas
    Vilnius University, Lithuania.
    Dorfling, Cecilia M.
    University of Pretoria, South Africa.
    van Rensburg, Elisabeth J.
    University of Pretoria, South Africa.
    Fostira, Florentia
    National Centre Science Research Demokritos, Greece.
    Konstantopoulou, Irene
    National Centre Science Research Demokritos, Greece.
    Garber, Judy
    Harvard University, MA USA.
    Godwin, Andrew K.
    University of Kansas, KS 66103 USA.
    Olah, Edith
    National Institute Oncol, Hungary.
    Narod, Steven A.
    University of Toronto, Canada.
    Rennert, Gad
    Clalit National Israeli Cancer Control Centre, Israel; Carmel Hospital, Israel; B Rappaport Fac Med, Israel.
    Shimon Paluch, Shani
    Chaim Sheba Medical Centre, Israel.
    Laitman, Yael
    Chaim Sheba Medical Centre, Israel.
    Friedman, Eitan
    Chaim Sheba Medical Centre, Israel; Tel Aviv University, Israel.
    Liljegren, Annelie
    Karolinska University Hospital, Sweden.
    Rantala, Johanna
    Karolinska University Hospital, Sweden.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Loman, Niklas
    University of Lund Hospital, Sweden.
    Imyanitov, Evgeny N.
    NN Petrov Institute Oncol, Russia.
    Hamann, Ute
    German Cancer Research Centre, Germany.
    Spurdle, Amanda B.
    Queensland Institute Medical Research, Australia.
    Healey, Sue
    Queensland Institute Medical Research, Australia.
    Weitzel, Jeffrey N.
    City Hope National Medical Centre, CA USA.
    Herzog, Josef
    City Hope National Medical Centre, CA USA.
    Margileth, David
    Care City Hope Clin Cancer Genet Commun Research Network, CA USA.
    Gorrini, Chiara
    University of Health Network, Canada.
    Esteller, Manel
    IDIBELL, Spain; University of Barcelona, Spain; Catalan Institute Research and Adv Studies ICREA, Spain.
    Gomez, Antonio
    IDIBELL, Spain.
    Sayols, Sergi
    IDIBELL, Spain.
    Vidal, Enrique
    IDIBELL, Spain.
    Heyn, Holger
    IDIBELL, Spain.
    Stoppa-Lyonnet, Dominique
    Institute Curie, France; Institute Curie, France; University of Paris 05, France.
    Leone, Melanie
    Hospital Civils Lyon, France.
    Barjhoux, Laure
    University of Lyon 1, France.
    Fassy-Colcombet, Marion
    Institute Curie, France.
    de Pauw, Antoine
    Institute Curie, France.
    Lasset, Christine
    University of Lyon 1, France; Centre Leon Berard, France.
    Fert Ferrer, Sandra
    Hop Hotel Dieu, France.
    Castera, Laurent
    Institute Curie, France.
    Berthet, Pascaline
    Centre Francois Baclesse, France.
    Cornelis, Francois
    Avicenne Hospital, France; Sud Francilien Hospital, France; University Hospital, France.
    Bignon, Yves-Jean
    University of Clermont Ferrand, France.
    Damiola, Francesca
    University of Lyon 1, France.
    Mazoyer, Sylvie
    University of Lyon 1, France.
    Sinilnikova, Olga M.
    Hospital Civils Lyon, France; University of Lyon 1, France.
    Maxwell, Christopher A.
    University of British Columbia, Canada.
    Vijai, Joseph
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Robson, Mark
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Kauff, Noah
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Corines, Marina J.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Villano, Danylko
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Cunningham, Julie
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Lee, Adam
    Mayo Clin, MN USA.
    Lindor, Noralane
    Mayo Clin Scottsdale, AZ USA.
    Lazaro, Conxi
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Easton, Douglas F.
    University of Cambridge, England.
    Offit, Kenneth
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Chenevix-Trench, Georgia
    Queensland Institute Medical Research, Australia.
    Couch, Fergus J.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Antoniou, Antonis C.
    University of Cambridge, England.
    Angel Pujana, Miguel
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers2015In: PLoS ONE, ISSN 1932-6203, Vol. 10, no 4, e0120020Article in journal (Refereed)
    Abstract [en]

    While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values greater than 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

  • 130.
    Block, Keith I.
    et al.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Gyllenhaal, Charlotte
    Block Centre Integrat Cancer Treatment, IL 60077 USA; National Cancer Centre, South Korea.
    Lowe, Leroy
    Getting Know Canc, Canada; University of Lancaster, England.
    Amedei, Amedeo
    University of Florence, Italy.
    Ruhul Amin, A. R. M.
    University of Florence, Italy.
    Amin, Amr
    University of Florence, Italy.
    Aquilano, Katia
    United Arab Emirates University, U Arab Emirates.
    Arbiser, Jack
    Atlanta Vet Adm Medical Centre, GA USA; Emory University, GA USA.
    Arreola, Alexandra
    University of Roma Tor Vergata, Italy.
    Arzumanyan, Alla
    University of N Carolina, NC 27599 USA.
    Salman Ashraf, S.
    Temple University, PA 19122 USA.
    Azmi, Asfar S.
    United Arab Emirates University, U Arab Emirates.
    Benencia, Fabian
    Wayne State University, MI USA.
    Bhakta, Dipita
    Ohio University, OH 45701 USA.
    Bilsland, Alan
    SASTRA University, India.
    Bishayeen, Anupam
    University of Glasgow, Scotland.
    Blain, Stacy W.
    Larkin Health Science Institute, FL USA.
    Block, Penny B.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Boosani, Chandra S.
    Suny Downstate Medical Centre, NY USA.
    Carey, Thomas E.
    Creighton University, NE 68178 USA.
    Carnero, Amancio
    University of Michigan, MI USA.
    Carotenuto, Marianeve
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Casey, Stephanie C.
    University of Naples Federico II, Italy.
    Chakrabarti, Mrinmay
    Stanford University, CA 94305 USA.
    Chaturvedi, Rupesh
    University of S Carolina, SC USA.
    Zhuo Chen, Georgia
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Chenx, Helen
    Jawaharlal Nehru University, India.
    Chen, Sophie
    University of British Columbia, Canada.
    Charlie Chen, Yi
    Ovarian and Prostate Cancer Research Lab, England; Alderson Broaddus University, PA USA.
    Choi, Beom K.
    National Cancer Centre, South Korea.
    Rosa Ciriolo, Maria
    United Arab Emirates University, U Arab Emirates.
    Coley, Helen M.
    University of Surrey, England.
    Collins, Andrew R.
    University of Oslo, Norway.
    Connell, Marisa
    Jawaharlal Nehru University, India.
    Crawford, Sarah
    So Connecticut State University, CT 06515 USA.
    Curran, Colleen S.
    University of Wisconsin, WI USA.
    Dabrosin, Charlotta
    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.
    Damia, Giovanna
    Ist Ric Farmacol Mario Negri, Italy.
    Dasgupta, Santanu
    University of Texas Health Science Centre Tyler, TX USA.
    DeBerardinis, Ralph J.
    University of Texas SW Medical Centre Dallas, TX 75390 USA.
    Decker, William K.
    Baylor Coll Med, TX 77030 USA.
    Dhawan, Punita
    Vanderbilt University, TN 37212 USA.
    Diehl, Anna Mae E.
    Duke University, NC 27710 USA.
    Dong, Jin-Tang
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Ping Dou, Q.
    United Arab Emirates University, U Arab Emirates.
    Drew, Janice E.
    University of Aberdeen, Scotland.
    Elkord, Eyad
    United Arab Emirates University, U Arab Emirates.
    El-Rayes, Bassel
    Emory University, GA 30322 USA.
    Feitelson, Mark A.
    University of N Carolina, NC 27599 USA.
    Felsher, Dean W.
    University of Naples Federico II, Italy.
    Ferguson, Lynnette R.
    University of Auckland, New Zealand.
    Fimognari, Carmela
    University of Auckland, New Zealand.
    Firestone, Gary L.
    University of Bologna, Italy.
    Frezza, Christian
    University of Calif Berkeley, CA 94720 USA.
    Fujii, Hiromasa
    University of Cambridge, England.
    Fuster, Mark M.
    Nara Medical University, Japan.
    Generali, Daniele
    University of Calif San Diego, CA 92103 USA; University of Calif San Diego, CA 92103 USA.
    Georgakilas, Alexandros G.
    University of Trieste, Italy.
    Gieseler, Frank
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Gilbertson, Michael
    National Technical University of Athens, Greece.
    Green, Michelle F.
    University Hospital Schleswig Holstein, Germany.
    Grue, Brendan
    Getting Know Canc, Canada.
    Guha, Gunjan
    Ohio University, OH 45701 USA.
    Halicka, Dorota
    Duke University, NC USA.
    Helferich, William G.
    Dalhousie University, Canada.
    Heneberg, Petr
    New York Medical Coll, NY 10595 USA.
    Hentosh, Patricia
    University of Illinois, IL 61820 USA.
    Hirschey, Matthew D.
    University Hospital Schleswig Holstein, Germany.
    Hofseth, Lorne J.
    Charles University of Prague, Czech Republic.
    Holcombe, Randall F.
    Old Domin University, VA USA.
    Honoki, Kanya
    Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
    Hsu, Hsue-Yin
    University of S Carolina, SC 29208 USA.
    Huang, Gloria S.
    Mt Sinai School Med, NY USA.
    Jensen, Lasse D.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jiang, Wen G.
    Cardiff University, Wales.
    Jones, Lee W.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Karpowicz, Phillip A.
    University of Windsor, Canada.
    Nicol Keith, W.
    SASTRA University, India.
    Kerkar, Sid P.
    Mayo Clin, MN USA.
    Khan, Gazala N.
    Henry Ford Hospital, MI 48202 USA.
    Khatami, Mahin
    National Institute Heatlh, MD USA.
    Ko, Young H.
    University of Maryland BioPark, MD USA.
    Kucuk, Omer
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Kulathinal, Rob J.
    University of N Carolina, NC 27599 USA.
    Kumar, Nagi B.
    University of S Florida, FL USA.
    Kwon, Byoung S.
    National Cancer Centre, South Korea; Tulane University, LA 70118 USA.
    Le, Anne
    Johns Hopkins University, MD USA.
    Lea, Michael A.
    Rutgers State University, NJ USA.
    Lee, Ho-Young
    Seoul National University, South Korea.
    Lichtor, Terry
    Rush University, IL 60612 USA.
    Lin, Liang-Tzung
    Taipei Medical University, Taiwan.
    Locasale, Jason W.
    Cornell University, NY 14853 USA.
    Lokeshwar, Bal L.
    Georgia Regents University, GA USA.
    Longo, Valter D.
    University of So Calif, CA USA.
    Lyssiotis, Costas A.
    University of Michigan, MI USA; University of Michigan, MI USA.
    MacKenzie, Karen L.
    Childrens Cancer Institute Australia, Australia.
    Malhotra, Meenakshi
    McGill University, Canada.
    Marino, Maria
    University of Rome Tre, Italy.
    Martinez-Chantar, Maria L.
    Technology Pk Bizkaia, Spain.
    Matheu, Ander
    Biodonostia Institute, Spain.
    Maxwell, Christopher
    Jawaharlal Nehru University, India.
    McDonnell, Eoin
    University Hospital Schleswig Holstein, Germany.
    Meeker, Alan K.
    Johns Hopkins University, MD 21205 USA.
    Mehrmohamadi, Mahya
    Cornell University, NY USA.
    Mehta, Kapil
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Michelotti, Gregory A.
    Duke University, NC 27710 USA.
    Mohammad, Ramzi M.
    United Arab Emirates University, U Arab Emirates.
    Mohammed, Sulma I.
    Purdue University, IN 47907 USA.
    James Morre, D.
    Mor NuCo Inc, IN USA.
    Muqbil, Irfana
    United Arab Emirates University, U Arab Emirates.
    Muralidhar, Vinayak
    Harvard University, MA USA; MIT, MA 02139 USA.
    Murphy, Michael P.
    MRC Mitochondrial Biol Unit, England.
    Purnachandra Nagaraju, Ganji
    Emory University, GA 30322 USA.
    Nahta, Rita
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Niccolai, Elena
    University of Florence, Italy.
    Nowsheen, Somaira
    Mayo Clin, MN USA.
    Panis, Carolina
    State University of West Parana, Brazil.
    Pantano, Francesco
    University of Campus Bio Med, Italy.
    Parslow, Virginia R.
    University of Auckland, New Zealand.
    Pawelec, Graham
    University of Tubingen, Germany.
    Pedersen, Peter L.
    Johns Hopkins University, MD USA.
    Poore, Brad
    Johns Hopkins University, MD USA.
    Poudyal, Deepak
    Charles University of Prague, Czech Republic.
    Prakash, Satya
    McGill University, Canada.
    Prince, Mark
    University of Michigan, MI USA.
    Raffaghello, Lizzia
    Ist Giannina Gaslini, Italy.
    Rathmell, Jeffrey C.
    University Hospital Schleswig Holstein, Germany.
    Kimryn Rathmell, W.
    University of Roma Tor Vergata, Italy.
    Ray, Swapan K.
    Stanford University, CA 94305 USA.
    Reichrath, Joerg
    Saarland University Hospital, Germany.
    Rezazadeh, Sarallah
    University of Rochester, NY 14627 USA.
    Ribatti, Domenico
    University of Bari, Italy.
    Ricciardiello, Luigi
    National Cancer Institute Giovanni Paolo II, Italy.
    Brooks Robey, R.
    University of Bologna, Italy; White River Junct Vet Affairs Medical Centre, VT USA.
    Rodier, Francis
    Geisel School Medical Dartmouth, NH USA; University of Montreal, Canada.
    Vasantha Rupasinghe, H. P.
    Institute Cancer Montreal, Canada.
    Luigi Russo, Gian
    University of Montreal, Canada.
    Ryan, Elizabeth P.
    Dalhousie University, Canada.
    Samadi, Abbas K.
    Dalhousie University, Canada.
    Sanchez-Garcia, Isidro
    CNR, Italy.
    Sanders, Andrew J.
    Cardiff University, Wales.
    Santini, Daniele
    University of Campus Bio Med, Italy.
    Sarkar, Malancha
    Colorado State University, CO 80523 USA.
    Sasada, Tetsuro
    Sanus Bioscience, CA USA.
    Saxena, Neeraj K.
    University of Salamanca, Spain.
    Shackelford, Rodney E.
    University of Miami, FL USA.
    Shantha Kumara, H. M. C.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Sharma, Dipali
    Kurume University, Japan.
    Shin, Dong M.
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Sidransky, David
    University of Maryland, MD 21201 USA.
    David Siegelin, Markus
    Louisiana State University, LA 71105 USA.
    Signori, Emanuela
    Johns Hopkins University, MD 21205 USA; Johns Hopkins University, MD USA.
    Singh, Neetu
    Johns Hopkins University, MD USA; King Georges Medical University, India.
    Sivanand, Sharanya
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Sliva, Daniel
    Institute Translat Pharmacol, Italy; Purdue Research Pk, IN USA.
    Smythe, Carl
    University of Sheffield, England.
    Spagnuolo, Carmela
    University of Montreal, Canada.
    Stafforini, Diana M.
    University of Utah, UT USA.
    Stagg, John
    University of Utah, UT USA.
    Subbarayan, Pochi R.
    University of Montreal, Canada.
    Sundin, Tabetha
    University of Miami, FL USA.
    Talib, Wamidh H.
    Sentara Healthcare, VA USA.
    Thompson, Sarah K.
    Appl Science University, Jordan.
    Tran, Phuoc T.
    Royal Adelaide Hospital, Australia.
    Ungefroren, Hendrik
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Vander Heiden, Matthew G.
    MIT, MA 02139 USA.
    Venkateswaran, Vasundara
    Johns Hopkins University, MD USA; University of Toronto, Canada.
    Vinay, Dass S.
    Tulane University, LA USA.
    Vlachostergios, Panagiotis J.
    Johns Hopkins University, MD USA; New York University, NY USA.
    Wang, Zongwei
    Johns Hopkins University, MD USA; Harvard University, MA USA.
    Wellendx, Kathryn E.
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Whelan, Richard L.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Yang, Eddy S.
    University of Alabama Birmingham, AL USA.
    Yang, Huanjie
    Harbin Institute Technology, Peoples R China.
    Yang, Xujuan
    Dalhousie University, Canada.
    Yaswen, Paul
    Lawrence Berkeley National Lab, CA USA.
    Yedjou, Clement
    Jackson State University, MS USA.
    Yin, Xin
    Nara Medical University, Japan.
    Zhu, Jiyue
    Washington State University, WA USA.
    Zollo, Massimo
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Designing a broad-spectrum integrative approach for cancer prevention and treatment2015In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 35, S276-S304 p.Article, review/survey (Refereed)
    Abstract [en]

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.

  • 131.
    Blockhuys, S.
    et al.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Celauro, E.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    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.
    Feizi, A.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, 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.
    Fierro-González, J.C.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Wittung-Stafshede, P.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Defining the human copper proteome and analysis of its expression variation in cancers.2017In: Metallomics : integrated biometal science, ISSN 1756-591X, Vol. 9, no 2, 112-123 p.Article in journal (Refereed)
    Abstract [en]

    Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that 'chaperone' the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic-molecular studies of Cu-dependent processes in cancer.

  • 132.
    Blockhuys, Stephanie
    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 Oncology. Chalmers, Sweden.
    Liu, Na
    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.
    Rani Agarwal, Nisha
    Chalmers, Sweden.
    Enejder, Annika
    Chalmers, Sweden.
    Loitto, Vesa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    X-radiation enhances the collagen type I strap formation and migration potentials of colon cancer cells2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 44, 71390-71399 p.Article in journal (Refereed)
    Abstract [en]

    Rectal cancer treatment still fails with local and distant relapses of the disease. It is hypothesized that radiotherapy could stimulate cancer cell dissemination and metastasis. In this study, we evaluated the effect of X-radiation on collagen type I strap formation potential, i.e. matrix remodeling associated with mesenchymal cell migration, and behaviors of SW480, SW620, HCT116 p53(+/+) and HCT116 p53(-/-) colon cancer cells. We determined a radiation-induced increase in collagen type I strap formation and migration potentials of SW480 and HCT116 p53(+/+). Further studies with HCT116 p53(+/+), indicated that after X-radiation strap forming cells have an increased motility. More, we detected a decrease in adhesion potential and mature integrin beta 1 expression, but no change in non-muscle myosin II expression for HCT116 p53(+/+) after X-radiation. Integrin beta 1 neutralization resulted in a decreased cell adhesion and collagen type I strap formation in both sham and X-radiated conditions. Our study indicates collagen type I strap formation as a potential mechanism of colon cancer cells with increased migration potential after X-radiation, and suggests that other molecules than integrin beta 1 and non-muscle myosin II are responsible for the radiation-induced collagen type I strap formation potential of colon cancer cells. This work encourages further molecular investigation of radiation-induced migration to improve rectal cancer treatment outcome.

  • 133.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Avoiding the first cesarean section-results of structured organizational and cultural changes2016In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 95, no 5, 580-586 p.Article in journal (Refereed)
    Abstract [en]

    IntroductionIn 2006 the overall rates of instrumental deliveries (10%) and cesarean sections (CS) (20%) were high in our unit. We decided to improve quality of care by offering more women a safe and attractive normal vaginal delivery. The target group was primarily nulliparous women at term with spontaneous onset of labor and cephalic presentation. Material and methodsImplementation of a nine-item list of structured organizational and cultural change in Linkoping 2006-15. The nine items include monitoring of obstetric results, recruitment of a midwife coordinator, risk classification of women, introduction of three different midwife competence levels, improved teamwork, obstetrical morning round, fetal monitoring skills, obstetrical skills training, and public promotion of the strategy. ResultsThe CS rate in nulliparous women at term with spontaneous onset of labor decreased from 10% in 2006 to 3% in 2015. During the same period the overall CS rate dropped from 20% to 11%. The prevalence of children born at the unit with umbilical cord pH &lt;7 and Apgar score &lt;4 at 5 min were the same over the years studied. At present, 95.2% of women delivering at our unit are satisfied with their delivery experience. ConclusionsThe CS rates have declined after implementing the nine items of organizational and cultural changes. It seems that a specific and persistent multidisciplinary activity with a focus on the Robson group 1 can reduce CS rates without increased risk of neonatal complications.

  • 134.
    Blomberg, Marie
    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.
    Fetma under graviditet ökar risken för både kvinna och barn: Kompetent omhändertagande kan minska riskökningen2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 48, 2156- p.Article in journal (Refereed)
    Abstract [sv]

    Fetma hos en gravid kvinna innebär ökad risk för missbildning hos fostret. Vid screeningultraljud upptäcks färre missbildningar än hos barn till normalviktiga kvinnor, men KUB-metoden för att upptäcka Downs syndrom är lika effektiv i alla BMI-grupper. Fetma hos kvinnan innebär ökad risk för gestationsdiabetes, preeklampsi, prematur förlossning och intrauterin fosterdöd. Öppningsskedet under förlossningen är förlängt hos kvinnor med BMI >30, men krystskedet är snabbt. Det finns ökad risk för atonisk postpartumblödning, vilket kan indicera profylaktisk behandling med uterotonika. Fetma hos kvinnan medför fler allvarliga komplikationer hos barnet under första levnadsveckan oavsett förlossningssätt.

  • 135.
    Blomberg, Marie
    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.
    Maternal Body Mass Index and Risk of Obstetric Anal Sphincter Injury2014In: BIOMED RESEARCH INTERNATIONAL, ISSN 2314-6133, Vol. 2014, no 395803Article in journal (Refereed)
    Abstract [en]

    Objective. To estimate the association between maternal obesity and risk of three different degrees of severity of obstetric anal sphincter injury. Methods. The study population consisted of 436,482 primiparous women with singleton term vaginal cephalic births between 1998 and 2011 identified in the Swedish Medical Birth Registry. Women were grouped into six categories of BMI. BMI 18.5-24.9 was set as reference. Primary outcome was third-degree perineal laceration, partial or total, and fourth-degree perineal laceration. Adjustments were made for year of delivery, maternal age, fetal head position at delivery, infant birth weight and instrumental delivery. Results. The overall prevalence of third-or four-degree anal sphincter injury was 6.6% (partial anal sphincter injury 4.6%, total anal sphincter injury 1.2%, unclassified as either partial and total 0.2%, or fourth degree lacerations 0.6%). The risk for a partial, total, or a fourth-degree anal sphincter injury decreased with increasing maternal BMI most pronounced for total anal sphincter injury where the risk among morbidly obese women was half that of normal weight women, OR 0.47 95% CI 0.28-0.78. Conclusion. Obese women had a favourable outcome compared to normal weight women concerning serious pelvic floor damages at birth.

  • 136.
    Blomberg, Marie
    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.
    Team-led hospital-based care reduced the number of obstetric interventions in ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA2016In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 95, no 11, 1320-1320 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 137.
    Blomberg, Marie
    et al.
    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.
    Birch Tyrberg, Rasmus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Kjölhede, Preben
    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.
    Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study2014In: BMJ Open, ISSN 2044-6055, Vol. 4, no 11, e005840- p.Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the associations between maternal age and obstetric and neonatal outcomes in primiparous women with emphasis on teenagers and older women. Design: A population-based cohort study. Setting: The Swedish Medical Birth Register. Participants: Primiparous women with singleton births from 1992 through 2010 (N=798 674) were divided into seven age groups: less than17 years, 17-19 years and an additional five 5-year classes. The reference group consisted of the women aged 25-29 years. Primary outcome: Obstetric and neonatal outcome. Results: The teenager groups had significantly more vaginal births (adjusted OR (aOR) 2.04 (1.79 to 2.32) and 1.95 (1.88 to 2.02) for age less than17 years and 1719 years, respectively); fewer caesarean sections (aOR 0.57 (0.48 to 0.67) and 0.55 (0.53 to 0.58)), and instrumental vaginal births (aOR 0.43 (0.36 to 0.52) and 0.50 (0.48 to 0.53)) compared with the reference group. The opposite was found among older women reaching a fourfold increased OR for caesarean section. The teenagers showed no increased risk of adverse neonatal outcome but presented an increased risk of prematurity less than32 weeks (aOR 1.66 (1.10 to 2.51) and 1.20 (1.04 to 1.38)). Women with advancing age (greater than= 30 years) revealed significantly increased risk of prematurity, perineal lacerations, preeclampsia, abruption, placenta previa, postpartum haemorrhage and unfavourable neonatal outcomes compared with the reference group. Conclusions: For clinicians counselling young women it is of importance to highlight the obstetrically positive consequences that fewer maternal complications and favourable neonatal outcomes are expected. The results imply that there is a need for individualising antenatal surveillance programmes and obstetric care based on age grouping in order to attempt to improve the outcomes in the age groups with less favourable obstetric and neonatal outcomes. Such changes in surveillance programmes and obstetric interventions need to be evaluated in further studies.

  • 138.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. 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.
    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.
    A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 29824Article in journal (Refereed)
    Abstract [en]

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.

  • 139.
    Boij, Roland
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Mjosberg, Jenny
    Karolinska Institute, Sweden.
    Svensson Arvelund, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    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.
    Matthiesen, Leif
    Linköping University, Faculty of Medicine and Health Sciences. 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. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    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.
    Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, no 4, 368-378 p.Article in journal (Refereed)
    Abstract [en]

    Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.

  • 140.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Metastatic Mechanisms in Malignant Tumors2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The ultimate cause of cancer related deaths is metastasis. This thesis is about three of the main human cancers; breast, colorectal and pancreatic cancer, that together account for more than 25% of the cancer-related deaths worldwide. The focus of the thesis is the spread of cancer, metastasis, and the aim was to investigate mechanisms that can be of importance for this process. We analyzed patient samples to validate the role of epithelialto-mesenchymal transition in vivo and found regulations of many related factors. However, these changes tend to fluctuate along the metastatic process, something which makes targeting complicated. We, moreover, focused on the influence of the tumor microenvironment for metastatic spread. In pancreatic cancer, the stroma constitutes the main part of many tumors. We analyzed the crosstalk between tumor and stromal cell and focused on the mediating inflammatory factor interleukin-1 (IL-1) and regulation of microRNAs. The results showed that the most commonly mutated factor in pancreatic cancer, KRAS, associates with the expression of IL-1 and subsequent activation of stromal cells. Blocking KRAS signaling together with IL-1 blockage give a more pronounced effect on in vitro proliferation and migration of cancer cells and suggests the use of a combination therapy. The cancer-associated activation of the stroma was found to be related to changes in microRNA expression. microRNA was analyzed separately in epithelial cells and stromal cells after microdissection of matched samples of primary and secondary tumors of breast and colorectal cancers. miR-214 and miR-199a were upregulated in stroma associated with progressive tumors and in pancreatic cancer stroma we could show that their expression alters the activation of stromal cells and thereby the growth and migratory ability of associated pancreatic tumor cells. In  breast and colorectal cancers we found several common microRNAs to be up- or downregulated in line with progression. We could show that one of these candidates, miR-18a, had a prognostic value in metastatic breast cancer. To further develop these studies we analyzed this microRNA in circulating microvesicles, i.e. exosomes, and investigated their role in the preparation of a pre-metastatic niche. MicroRNAs are stable biomarkers in the circulation, especially protected in exosomes, which can moreover specifically deliver their message to recipient cells. These studies facilitate the understanding of metastatic behavior and suggest new targets to stop cancer metastasis.

  • 141.
    Bojmar, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Ellegard, Sander
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Björnsson, Bergthor
    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.
    Hallböök, Olof
    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.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    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.
    Sandström, Per
    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.
    The Role of MicroRNA-200 in Progression of Human Colorectal and Breast Cancer2013In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 12, 84815- p.Article in journal (Refereed)
    Abstract [en]

    The role of the epithelial-mesenchymal transition (EMT) in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200 ZEB E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMTmarkers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200 - ZEB - E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.

  • 142.
    Bojmar, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    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.
    Olsson, Hans
    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.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    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.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuscript (preprint) (Other academic)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 143.
    Borendal Wodlin, Ninnie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Kjölhede, Preben
    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.
    Snabbspår har fördelar vid elektiv gynekologisk kirurgi.2014In: Läkartidningen, ISSN 0023-7205, Vol. 111, no 25-26, 2-7 p.Article in journal (Refereed)
    Abstract [en]

    Fast-track is a multimodal strategy aimed at achieving an improved and accelerated postoperative recovery. The strategy combines unimodal evidence-based interventions concerning preoperative preparation, peroperative principles and postoperative care. There is substantial evidence for the benefits of following fast-track concepts in general elective surgery to enhance postoperative recovery. The main findings of this review are that there are benefits likewise within elective gynecological surgery, but studies of quality of life, patient satisfaction and health economics are needed. Studies of fast-track within non-elective surgery and gynaecological oncology surgery are lacking. Widespread information and education is needed to improve the rate of implementation of fast-track. Comprehensive involvement of the entire staff dealing with the patient in the perioperative period is crucial to ensure implementation and development of surgical care aiming for enhanced postoperative recovery.

  • 144.
    Borneskog, C.
    et al.
    Uppsala University, Sweden .
    Lampic, C.
    Karolinska Institute, Sweden .
    Sydsjö, Gunilla
    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.
    Bladh, Marie
    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 Gynecology and Obstetrics UHL.
    Skoog Svanberg, A.
    Uppsala University, Sweden .
    How do lesbian couples compare with heterosexual in vitro fertilization and spontaneously pregnant couples when it comes to parenting stress?2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 5, 537-545 p.Article in journal (Refereed)
    Abstract [en]

    AimTo study parenting stress in lesbian parents and to compare that stress with heterosexual parents following in vitro fertilisation (IVF) or spontaneous pregnancies. MethodsThis survey took place during 2005-2008 and was part of the Swedish multicentre study on gamete donation. It comprised 131 lesbian parents, 83 heterosexual IVF parents, who used their own gametes, and 118 spontaneous pregnancy parents. The participants responded to the questionnaire when the child was between 12 and 36-months-old and parenting stress was measured by the Swedish Parenting Stress Questionnaire (SPSQ). ResultsLesbian parents experienced less parenting stress than heterosexual IVF parents when it came to the General Parenting Stress measure (p=0.001) and the subareas of Incompetence (pless than0.001), Social Isolation (p=0.033) and Role Restriction (p=0.004). They also experienced less parenting stress than heterosexual spontaneous pregnancy couples, according to the Social Isolation subarea (p=0.003). Birth mothers experienced higher stress than co-mothers and fathers, according to the Role Restriction measure (p=0.041). ConclusionThese are reassuring findings, considering the known challenges that lesbian families face in establishing their parental roles and, in particular, the challenges related to the lack of recognition of the co-mother.

  • 145.
    Borneskog, Catrin
    et al.
    Uppsala University, Sweden.
    Lampic, Claudia
    Karolinska Institute, Sweden.
    Sydsjö, Gunilla
    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.
    Bladh, Marie
    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.
    Skoog Svanberg, Agneta
    Uppsala University, Sweden.
    Relationship satisfaction in lesbian and heterosexual couples before and after assisted reproduction: a longitudinal follow-up study2014In: BMC Women's Health, ISSN 1472-6874, Vol. 14, no 154Article in journal (Refereed)
    Abstract [en]

    Background: More and more lesbian couples are planning parenthood through donor insemination and IVF and the number of planned lesbian families is growing in Sweden and other western countries. Research has shown that lesbian couples report as much overall satisfaction in their relationships as do heterosexual couples. However, although parenthood is highly desired, many parents are unaware of the demands of parenthood and the strain on their relationship that the arrival of the baby might bring. The aim of this study was to compare lesbian and heterosexual couples? perceptions of relationship satisfaction at a three-year follow up after assisted reproduction. Methods: The present study is a part of the Swedish study on gamete donation, a prospective longitudinal cohort study. The present study constitutes a three-year follow up assessment of lesbian and heterosexual couples after assisted reproduction. Participants requesting assisted reproduction at all fertility clinics performing gamete donation in Sweden, were recruited consecutively during 2005? 2008. A total of 114 lesbian women (57 treated women and 57 partners) and 126 heterosexual women and men (63 women and 63 men) participated. Participants responded to the ENRICH inventory at two time points during 2005? 2011; at the commencement of treatment (time point 1) and about three years after treatment termination (time point 3). To evaluate the bivariate relationships between the groups (heterosexual and lesbian) and socio-demographic factors Pearsons Chi- square test was used. Kolmogorov-Smirnov test was used for testing of normality, Mann? Whitney U-test to examine differences in ENRICH between the groups and paired samples t-test to examine scores over time. Results: Lesbian couples reported higher relationship satisfaction than heterosexual couples, however the heterosexual couples satisfaction with relationship quality was not low. Both lesbian and heterosexual couples would be classified accordingly to ENRICH-typology as vitalized or harmonious couples. Conclusions: At a follow-up after assisted reproduction with donated sperm, lesbian couples reported stable relationships and a high satisfaction with their relationships, even when treatment was unsuccessful.

  • 146.
    Bostner, Josefine
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    The Akt/mTOR Pathway and Estrogen Receptor Phosphorylations: a crosstalk with potential to predict tamoxifen resistance in breast cancer2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Estrogen receptor α content is the primary breast cancer biomarker distinguishing the patients responsive from the non-responsive to endocrine treatments. Tamoxifen is an estrogen competitor with large potential to treat breast cancer patients and prolongs time to recurrence. Despite the estrogen receptor positivity and tamoxifen treatment, many women face recurrence of the disease. An important mechanism of resistance to endocrine treatments is upregulated growth factor signaling, and the subsequent effect on the estrogen receptor, rendering an active receptor that stimulates cell proliferation or reduced estrogen-receptor dependence.

    This thesis concerns the investigation of biomarkers, as a complement to the existing markers, for determining optimal treatment for patients with primary invasive breast cancer. Randomized patient tumor materials were used in order to measure variations in gene copies, proteins, and protein phosphorylations and to further relate these variations to time-to-recurrence. Endocrine untreated groups within the patient tumor sets gave us the opportunity to study the prognostic potential of selected markers and to compare tamoxifen-treated patients with endocrine untreated, thus obtaining a treatment-predictive value of each marker or marker combination.

    In endocrine-dependent cancer the 11q13 chromosomal region is frequently amplified, harboring the genes encoding the cell cycle stimulator cyclin D1 and the estrogen receptor phosphorylating kinase Pak1, respectively. Amplification of the genes was associated with reduced time-torecurrence, indicating a prognostic value, whereas PAK1 gene amplification predicted reduced response to tamoxifen treatment. Moreover, the protein expression of Pak1 tended to predict treatment response, which led to the investigation of this protein in a larger cohort. Together with one of its targets, the estrogen receptor phosphorylation at serine 305, Pak1 predicted reduced response to tamoxifen treatment when detected in the nucleus of tumor cells, suggesting activation of this pathway as a mechanism for tamoxifen-treatment resistance. The estrogen receptor is phosphorylated by several growth factor stimulated kinases. The role of serine-167 phosphorylation has been debated, with inconsistent results. To study the biomarker value of this site the upstream activity of Akt, mTOR, and the S6 kinases were analyzed individually and in combinations. As a prognostic factor, serine 167 indicated an improved breast cancer survival, and as a treatment predictive factor we could not detect a significant value of serine 167 as a single marker. However, in combination with serine 305, and Akt/mTOR-pathway activation, the response to tamoxifen treatment was reduced. The mTOR effector protein S6K1 was found to be associated with HER2 positivity and a worse prognosis. In the group of patients with S6K1 accumulation in the tumor cell nuclei, treatment did not prolong time-to-recurrence, similarly as observed with expression of active S6 kinases. In vitro, a simultaneous knockdown of the S6 kinases in estrogen receptor-positive breast cancer cells resulted in G1 arrest, and tamoxifen-induced G1 arrest was in part S6 kinase dependent.

    The results presented herein suggest biomarkers that would improve treatment decisions in the clinic, specifically for estrogen receptor-positive breast cancer and tamoxifen treatment but in a broader perspective, also for other endocrine treatments and targeted treatments.

  • 147.
    Bostner, Josefine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Perez-Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Franzén, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Konstantinell, Aelita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fornander, Tommy
    Karolinska University Hospital, Sweden .
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    S6 kinase signaling and tamoxifen response in breast cancer cells and in two randomized breast cancer cohorts2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Detecting signals in the mammalian target of rapamycin (mTOR), and the estrogen receptor (ER) pathways for prediction of treatment response may be a future clinical tool in primary breast cancer. Here, we investigated the validity and value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen sensitivity in vitro and in two independent tamoxifen randomized postmenopausal breast cancer cohorts. In addition, the prognostic value of the S6Ks was evaluated. A simultaneous knockdown of the S6Ks in ER-positive breast cancer cells resulted in G1 arrest, and tamoxifen-induced G1 arrest was in part S6K1+S6K2 dependent, suggesting separate roles in proliferation and in tamoxifen response. We found S6K1 to correlate with HER2 and cytoplasmic Akt activity, whereas S6K2 and phosphorylated S6K were closer connected with ER positivity, low proliferation and nucleic p-Akt. Treatment prediction and prognosis were evaluated by immunohistochemical staining. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen treatment effect, compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation. Patients with a combination of S6K1 nuclear accumulation and S6K2 cytoplasmic accumulation in the tumor cells had no tamoxifen benefit. Also, S6K1 and S6K2 activation, indicated by p-S6K-t389 expression, was associated with low benefit from tamoxifen compared with untreated patients. In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis. This was not evident for variations in S6K2 or p-S6K-t389 expression.

    In conclusion, the mTOR targeted kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity andintracellular localization may provide biomarkers for breast cancer treatment, allowing for identification of a group of patients less likely tobenefit from tamoxifen and thus in need of an alternative or additional treatment.

  • 148.
    Bostner, Josefine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Elin
    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.
    Bivik Eding, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Perez-Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Franzén, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Konstantinell, Aelita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Nordenskjöld, Bo
    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.
    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.
    S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts2015In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, no 3, 331-343 p.Article in journal (Refereed)
    Abstract [en]

    Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, Pless than0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.

  • 149.
    Bostner, Josefine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Pandiyan, Muneeswaran J.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Westman, Hanna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Skoog, Lambert
    Stockholm S Gen Hospital, Sweden .
    Fornander, Tommy
    Karolinska University Hospital, Sweden .
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Activation of Akt, mTOR, and the estrogen receptor as a signature to predict tamoxifen treatment benefit2013In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 137, no 2, 397-406 p.Article in journal (Refereed)
    Abstract [en]

    The frequent alterations of the PI3K/Akt/mTOR-growth signaling pathway are proposed mechanisms for resistance to endocrine therapy in breast cancer, partly through regulation of estrogen receptor alpha (ER) activity. Reliable biomarkers for treatment prediction are required for improved individualized treatment. We performed a retrospective immunohistochemical analysis of primary tumors from 912 postmenopausal patients with node-negative breast cancer, randomized to either tamoxifen or no adjuvant treatment. Phosphorylated (p) Akt-serine (s) 473, p-mTOR-s2448, and ER phosphorylations-s167 and -s305 were evaluated as potential biomarkers of prognosis and tamoxifen treatment efficacy. High expression of p-mTOR indicated a reduced response to tamoxifen, most pronounced in the ER+/progesterone receptor (PgR) + subgroup (tamoxifen vs. no tamoxifen: hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.31-2.38; P = 0.78), whereas low p-mTOR expression predicted tamoxifen benefit (HR, 0.29; 95 % CI, 0.18-0.49; P = 0.000002). In addition, nuclear p-Akt-s473 as well as p-ER at -s167 and/or -s305 showed interaction with tamoxifen efficacy with borderline statistical significance. A combination score of positive pathway markers including p-Akt, p-mTOR, and p-ER showed significant association with tamoxifen benefit (test for interaction; P = 0.029). Cross-talk between growth signaling pathways and ER-signaling has been proposed to affect tamoxifen response in hormone receptor-positive breast cancer. The results support this hypothesis, as an overactive pathway was significantly associated with reduced response to tamoxifen. A clinical pre-treatment test for cross-talk markers would be a step toward individualized adjuvant endocrine treatment with or without the addition of PI3K/Akt/mTOR pathway inhibitors.

  • 150.
    Boström, A.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Thulin, K.
    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 Orthopaedics in Norrköping.
    Fredriksson, M.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Reese, D.
    IFK Norrköping, Norrköping, Sweden.
    Rockborn, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Hammar, Mats
    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.
    Risk factors for acute and overuse sport injuries in Swedish children 11 to 15 years old: What about resistance training with weights?2016In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, no 3, 317-323 p.Article in journal (Refereed)
    Abstract [en]

    To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48–51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50–55% vs 46%, 95% CI 43–48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries.

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