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  • 1151. Willmer, Mikaela
    et al.
    Berglind, Daniel
    Thorell, Anders
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Uddén, Joanna
    Raoof, Mustafa
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Tynelius, Per
    Ghaderi, Ata
    Näslund, Erik
    Rasmussen, Finn
    Changes in BMI and Psychosocial Functioning in Partners of Women Who Undergo Gastric Bypass Surgery for Obesity2015In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 2, p. 319-324Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There is very little research exploring the effects of Roux-en-Y gastric bypass surgery (RYGB) on the patient's partner. The aim of the present study was to investigate longitudinally whether male partners of female RYGB patients were affected in terms of BMI, sleep quality, body dissatisfaction, depression, and anxiety.

    METHODS:

    Thirty-seven women, with partners who were willing to participate, were recruited from RYGB waiting lists at five Swedish hospitals. Data collection took place during two home visits, 3 months before and 9 months after RYGB surgery. Anthropometrical data were documented, and both women and men completed the Hospital Anxiety and Depression Scale (HADS) and the Karolinska Sleep Questionnaire (KSQ). The men also completed the Male Body Dissatisfaction Scale (MBDS).

    RESULTS:

    The men's BMI changes between the two time points that were analysed using general estimating equation (GEE) regression. Their BMI decreased significantly (β = -0.9, p = 0.004). The change was more pronounced in the 26 men who had a baseline BMI of ≥25 (β = -1.4, p < 0.001). Fixed-effects regression showed a statistically significant association between the men's weight loss and that of the women (β = 0.3, p = 0.004). There were no significant changes in the men's HADS, KSQ, or MBDS scores.

    CONCLUSIONS:

    Overweight/obese male partners of RYGB patients also lose weight during the first 9 months post-operatively. However, symptoms of body dissatisfaction, anxiety, and depression remain unchanged, as does self-reported sleep quality.

  • 1152.
    Winerdal, Malin E.
    et al.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Krantz, David
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Hartana, Ciputra A.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Zirakzadeh, Ali A.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Linton, Ludvig
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Bergman, Emma A.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Rosenblatt, Robert
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden; Karolinska Inst, Stockholm South Gen Hosp, Dept Urol, Stockholm, Sweden.
    Vasko, Janos
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden.
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
    Winerdal, Max
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Marits, Per
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Sherif, Amir
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Winqvist, Ola
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness2018In: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 6, no 5, p. 528-538Article in journal (Refereed)
    Abstract [en]

    Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This discrepancy has partly been attributed to the shear misidentification of Tregs, but also to the inflammatory profile of the tumor. Our aim was to determine whether tumor-infiltrating Forkhead box P3+ (FOXP3+) cells confer a stable Treg phenotype and to investigate putative beneficial Treg functions, focusing on tumor-promoting inflammatory pathways in UBC. Patients (n = 52) with suspected UBC were prospectively included. We show, by using a broad range of analytical approaches, that tumor-infiltrating CD4+FOXP3+ T cells in UBC phenotypically, functionally, and epigenetically represent a true Treg population. At the invasive front of UBC tumors, we found an inverse relationship between Treg frequency and expression of matrix metalloproteinase 2 (MMP2), a key proinvasive factor induced by tumor-promoting inflammation. Correspondingly, a significant, dose-dependent Treg-mediated downregulation of MMP2 protein and mRNA expression was observed in both macrophages and UBC cells. Also, we found that Treg frequency specifically at the invasive front positively correlated with survival. Thus, we identify Treg-mediated suppression of MMP2 in the tumor microenvironment as a mechanism explaining the paradoxical positive prognostic impact of tumor-infiltrating Tregs in UBC.

  • 1153. Winstedt, L.
    et al.
    Malmqvist, U.
    Bjorck, L.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bengtsson, M.
    Uppsala University.
    Kjellman, C.
    The IgG Specific Cysteine Protease IdeS: A Novel Candidate Drug for Pre-Transplantation Desensitization2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, p. 666-666Article in journal (Other academic)
  • 1154. Winstedt, L.
    et al.
    Malmqvist, U.
    Bjorck, L.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kjellman, C.
    The IgG Specific Cysteine Protease IdeS: A Novel Candidate Drug for Pre-Transplantation Desensitization.2014In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 98, p. 666-666Article in journal (Other academic)
  • 1155.
    Wintzell, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Anterior shoulder dislocation: Aspects of alternative methods of treatment and MR imaging1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sixty patients (16-30 years) with traumatic primary anterior shoulder dislocation were allocated to arthroscopic lavage or non-operative treatment. The arthroscopic lavage group had a lower recurrence rate, better functional outcome and anterior stability after one year.

    Thirty patients were treated with arthroscopic lavage or non-operatively after traumatic primary anterior shoulder dislocation in a randomised trial. At two year follow-up the recurrence rate was lowerin the lavage group (20%) than in the non-operated group (60%).

    Sixteen patients were allocated to lavage or non-operative treatment after primary anterior shoulder dislocation. Weekly ultrasound examination of the pathologic joint effusion showed a significant more rapid reduction of joint effusion in the patients treated with lavage.

    Twenty-eight recurrent anterior dislocating shoulders in each of two groups, were operated on with open Bankart procedure using suture-anchor fixation or screw-fixation with a washer. Evaluation (>=2 years) revealed a better anterior stability, better functional outcome and wider external rotation for the patients operated with the suture-anchor technique.

    Twelve shoulders with anterior instability were assessed with an alternative MR technique, using the apprehension test position, an open MR device and with indirect gadodiamide MR arthrography. The apprehension test position showed to be beneficial in evaluating capsulo-labral and skeletal lesions associated with anterior shoulder instability.

    Sixteen patients with anterior shoulder instability were examined with indirect MR arthrography in the ABER (abduction, external rotation) and the apprehension position for comparison. The apprehension position showed to be a more beneficial MRI position than the ABER position in indirect arthrography.

    Fourteen patients with recurrent anterior shoulder instability and 6 shoulder healthy controls were examined with intravenous MR arthrography, using standard (0.1 mmol/kg) and triple dose (0.3 mmol/kg) of gadodiamide. Joint fluid enhancement in the unstable shoulders were 155% with standard dose while the triple dose only gave a 39% further increase. The standard dose produced an enhancement of 84-93% in the stable shoulders while the triple dose resulted in an further increase of 109-115%.

  • 1156.
    Wolf, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Osteoarthritis of the Hip and Uncemented Total Hip Arthroplasty: Effects of Immediate Weight Bearing on Implant Stability, Bone Mineral Density, and Body Composition2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The initial recommendation for the postoperative regime after uncemented total hip arthroplasty (THA) was 6-12 weeks of partial weight bearing (PWB) to obtain a stable implant position during bone ingrowth. In recent years patients with uncemented THA have increasingly practiced full weight bearing (FWB) after surgery, which has largely been based on clinical experience rather than on scientific evidence. The aim of this thesis was to investigate the effects of FWB versus PWB for 3 months on the stability of the implants and on bone mineral density (BMD), as well as body composition (BC) of the lower extremities.

    We used radiostereometric analysis (RSA) to measure implant micromotion and dual X-ray absorptiometry (DXA) to measure BMD and BC. Forty-six patients with strictly unilateral osteoarthritis of the hip (OAH) received uncemented THA. These patients were then randomized to the FWB or PWB groups and followed for 5 years.

    In a preoperative cross-sectional study the BMD of the hip and heel were compared between the OAH-affected side and the healthy side. The study showed an increase of BMD at the femoral neck and a decrease at the total hip and trochanter. The results of a RSA study of cup stability showed that there might be minimal movement in medial and proximal directions during the first postoperative week. These results indicate that the RSA baseline investigation of uncemented cups should be performed as early as possible after the first postoperative day. FWB had no adverse effects on the stability of the uncemented press-fit cups or the uncemented cementless Spotorno (CLS) femoral stems after a 5-year follow-up. There was no difference in periprosthetic BMD around the CLS stem regardless of the postoperative weight bearing regime. All zones around the femoral stem indicated a recovery in BMD toward baselines, except the calcar region, which showed progressive loss in BMD to -22% at 5 years post-surgery. FWB had no effect on the changes in BC after surgery.

    In conclusion, FWB is safe in uncemented THA in terms of stability, BMD and BC. Furthermore, THA apparently counteracts age-related changes in BC but not in BMD.

    List of papers
    1. Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips
    Open this publication in new window or tab >>Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips
    Show others...
    2009 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 80, no 3, p. 308-313Article in journal (Refereed) Published
    Abstract [en]

    Introduction In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs. Patients and methods 40 patients with strictly unilateral OAH were cross-sectionally investigated with DXA at the hips and heels bilaterally as well as body composition of the legs. 3 regions of interest in the proximal femur were measured: femoral neck (FN), trochanter (TR), and total hip (TH). The design of the study allowed us to perform paired t-test between the OAH side and the healthy side. Results BMD was increased by 4.1% in FN, and reduced by 8.3% in TR and 4.1% in TH (p < 0.001 for all comparisons). Interpretation The differences in BMD, with decrease in the trochanter and increase in the femoral neck, may offer an explanation for the pattern of hip fractures seen in osteoarthritis. External rotation of the hip cannot explain the differences in BMD.

    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-111771 (URN)10.3109/17453670903039528 (DOI)000268569700009 ()19593721 (PubMedID)
    Available from: 2009-12-21 Created: 2009-12-21 Last updated: 2017-12-12Bibliographically approved
    2. The optimal timing of baseline radiostereometric analysis of uncemented press fit cups
    Open this publication in new window or tab >>The optimal timing of baseline radiostereometric analysis of uncemented press fit cups
    Show others...
    2010 (English)In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 99, no 4, p. 244-249Article in journal (Refereed) Published
    Abstract [en]

    Background and Aims: The baseline Radiostereometric analysis (RSA) is usually performed during the first postoperative week. We investigated the micromotion of two uncemented press fit acetabular cups during the first week after total hip arthroplasty.

    Material and Methods: All study patients had unilateral osteoarthritis of the hip and received an uncemented THA combination consisting of a CLS stem and either an Allofit or an Interop acetabular cup. The study group consisted of 24 patients who underwent RSA within 1 hour after skin closure, and at 1 and 7 days after surgery.

    Results: The upper limit of the 95% confidence interval for micromotion was less than or close to the precision of the method for all studied directions during the first week after surgery. Mean values indicate proximal and medial translation of the uncemented cup at one week.

    Conclusions: We found only minimal micromotion, barely above the precision limit, measured as medial and proximal translations of these uncemented cups. This indicates that the first postoperative RSA measurement following a primary THA with an uncemented press fit acetabular cup should be made as early as possible after the first postoperative day.

    Keywords
    RSA, baseline examination, THA, uncemented cup, optimal timing, micromotion, weight bearing, muscle tonus
    National Category
    Medical and Health Sciences
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-131033 (URN)000285817800013 ()
    Available from: 2010-09-21 Created: 2010-09-21 Last updated: 2017-12-12Bibliographically approved
    3. Effects of different weight bearing regimes on stability of press fit cups: A randomized study with 5 years of follow-up using radiostereometry
    Open this publication in new window or tab >>Effects of different weight bearing regimes on stability of press fit cups: A randomized study with 5 years of follow-up using radiostereometry
    Show others...
    (English)Article in journal (Refereed) Submitted
    Abstract [en]

    There is little evidence supporting immediate weight bearing after uncemented THA. Thirty-seven patients with unilateral osteoarthritis of the hip received a press fit cup. They were randomized to immediate full weight bearing or partial weight bearing for 3 months. At 5 years we found no difference in micromotion as assessed with radiostereometry. Numerically there was more proximal translation and increased inclination with immediate weight bearing, but these values barely exceeded the precision limit for the method. Pooled data for the two groups revealed translations of 0.1-0.3 mm and rotations of 0.2-0.3° over the 5 year follow-up period. To conclude, we found no adverse effects of immediate weight bearing after THA on stability of these press fit cups. Early mobilization might have other advantages.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-131035 (URN)
    Available from: 2010-09-21 Created: 2010-09-21 Last updated: 2013-08-16Bibliographically approved
    4. A randomized study using DXA and RSA in 38 patients followed for 5 years
    Open this publication in new window or tab >>A randomized study using DXA and RSA in 38 patients followed for 5 years
    Show others...
    2010 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 3, p. 286-291Article in journal (Refereed) Published
    Abstract [en]

    Background and purpose: There is no real consensus on the best rehabilitation regime after uncemented total hip arthroplasty. Theoretically, bone ingrowth into the implant should benefit from initial partial weight bearing. We investigated whether the degree of postoperative weight bearing influences the periprosthetic bone mineral density (BMD) and/or the stability of the CLS stem.

    Patients and methods: 38 patients received an uncemented CLS stem and were randomized to either unrestricted postoperative weight bearing or to partial weight bearing for 3 months. Periprosthetic BMD was measured in the 7 Gruen zones with DXA and the stability of the femoral stem was assessed by radiostereometric analyses (RSA) after surgery and at 3, 12, 24, and 60 months.

    Results: Periprosthetic BMD was not influenced by the type of postoperative weight bearing. BMD was reduced by 8-15% in all Gruen zones at 3 months. Restoration toward initial BMD was observed in all zones except in zone 7 (calcar region), where BMD was decreased by 22% at 5 years. Immediate weight bearing after surgery did not influence the stability of the CLS stem, as assessed by RSA.

    Interpretation: Immediate full weight bearing after uncemented total hip arthroplasty is safe. There is no difference in the periprosthetic BMD or stability of the stem as measured with RSA compared to partial weight bearing for 3 months. BMD is decreased by more than 20% in the calcar region around a CLS stem after 5 years.

    Keywords
    weight bearing, DXA, periprosthetic BMD, RSA, uncemented CLS stem
    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-131005 (URN)10.3109/17453674.2010.487238 (DOI)20446828 (PubMedID)
    Available from: 2010-09-21 Created: 2010-09-20 Last updated: 2017-12-12Bibliographically approved
    5. Effects of postoperative weight-bearing on body composition and bone mineral density after uncemented total hip arthroplasty
    Open this publication in new window or tab >>Effects of postoperative weight-bearing on body composition and bone mineral density after uncemented total hip arthroplasty
    Show others...
    2013 (English)In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 45, no 5, p. 498-503Article in journal (Refereed) Published
    Abstract [en]

    Objective:

    To investigate whether a postoperative weight-bearing regimen affects changes in bone mineral density and body composition after uncemented total hip arthroplasty, and to investigate the changes over a 5-year period after the surgical procedure.

    Design:

    Secondary analysis of a previous randomized controlled trial.

    Methods:

    A total of 39 patients were randomized to immediate full weight-bearing or partial weight-bearing for 3 months. Dual-energy X-ray absorptiometry was used to measure bone mineral density of the contralateral hip and both heels and to measure body composition.

    Results:

    The weight-bearing regimen had no effect on change in bone mineral density or body composition after 3 and 12 months. At 5 years, there was a decrease in bone mineral density of 3% in the total body and 2-3% in the contralateral hip regions. At 5 years we found a decrease in total body bone mineral content of 5%, but no changes in fat mass or lean mass compared with preoperative values.

    Conclusion:

    The postoperative weight-bearing regimen had no effect on changes in body composition or bone mineral density. Five years after total hip arthroplasty there was a decrease in bone mineral content and bone mineral density, but no changes in lean mass or fat mass.

    Keywords
    osteoarthritis of the hip; uncemented total hip arthroplasty; DXA; weight-bearing; body composition; bone mineral density
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-199774 (URN)10.2340/16501977-1140 (DOI)000320345700012 ()23571688 (PubMedID)
    Available from: 2013-05-14 Created: 2013-05-14 Last updated: 2017-12-06Bibliographically approved
  • 1157.
    Wolf, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mattsson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    A randomized study using DXA and RSA in 38 patients followed for 5 years2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 3, p. 286-291Article in journal (Refereed)
    Abstract [en]

    Background and purpose: There is no real consensus on the best rehabilitation regime after uncemented total hip arthroplasty. Theoretically, bone ingrowth into the implant should benefit from initial partial weight bearing. We investigated whether the degree of postoperative weight bearing influences the periprosthetic bone mineral density (BMD) and/or the stability of the CLS stem.

    Patients and methods: 38 patients received an uncemented CLS stem and were randomized to either unrestricted postoperative weight bearing or to partial weight bearing for 3 months. Periprosthetic BMD was measured in the 7 Gruen zones with DXA and the stability of the femoral stem was assessed by radiostereometric analyses (RSA) after surgery and at 3, 12, 24, and 60 months.

    Results: Periprosthetic BMD was not influenced by the type of postoperative weight bearing. BMD was reduced by 8-15% in all Gruen zones at 3 months. Restoration toward initial BMD was observed in all zones except in zone 7 (calcar region), where BMD was decreased by 22% at 5 years. Immediate weight bearing after surgery did not influence the stability of the CLS stem, as assessed by RSA.

    Interpretation: Immediate full weight bearing after uncemented total hip arthroplasty is safe. There is no difference in the periprosthetic BMD or stability of the stem as measured with RSA compared to partial weight bearing for 3 months. BMD is decreased by more than 20% in the calcar region around a CLS stem after 5 years.

  • 1158.
    Wolf, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips2009In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 80, no 3, p. 308-313Article in journal (Refereed)
    Abstract [en]

    Introduction In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs. Patients and methods 40 patients with strictly unilateral OAH were cross-sectionally investigated with DXA at the hips and heels bilaterally as well as body composition of the legs. 3 regions of interest in the proximal femur were measured: femoral neck (FN), trochanter (TR), and total hip (TH). The design of the study allowed us to perform paired t-test between the OAH side and the healthy side. Results BMD was increased by 4.1% in FN, and reduced by 8.3% in TR and 4.1% in TH (p < 0.001 for all comparisons). Interpretation The differences in BMD, with decrease in the trochanter and increase in the femoral neck, may offer an explanation for the pattern of hip fractures seen in osteoarthritis. External rotation of the hip cannot explain the differences in BMD.

  • 1159. Wollert, S
    et al.
    Rasmussen, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lundberg, C
    Gerdin, B
    Arvidsson, D
    Haglund, U
    Inhibition of CD18-dependent adherence of polymorphonuclear leukocytes does not affect liver oxygen consumption in fecal peritonitis in pigs.1993In: Circulatory shock, ISSN 0092-6213, Vol. 41, no 4, p. 230-8Article in journal (Refereed)
    Abstract [en]

    We tested the hypothesis that circulating polymorphonuclear leukocytes (PMNs), adhering to endothelium of the liver vascular bed are involved in the alterations of the liver oxygen delivery (DO2) and consumption (VO2) that is a result of fecal peritonitis in pigs. Twenty-two pigs were divided into three groups. Animals in group I (n = 7) served as controls. Fecal peritonitis was induced in groups II (n = 7) and III (n = 8). Animals in group III were pretreated with IB4, a monoclonal anti-CD18 antibody inhibiting adherence of PMNs to the endothelium. Peritonitis increased liver VO2 in groups II and III in spite of decreased liver DO2. In group I, circulating PMNs increased during the experimental period. Sepsis caused a decrease in the number of circulating PMNs in group II, an effect that was fully counteracted in group III, where the number of PMNs rose to control level. Myeloperoxidase activity and morphometric determination of PMN infiltration in liver biopsies virtually paralleled the circulating PMN count. Although fecal peritonitis is followed by a CD18-dependent leukopenia that can be counteracted by pretreatment with an anti-CD18 antibodies, this treatment does not affect the alteration in liver VO2 and DO2 observed.

  • 1160. Wu, Lang
    et al.
    Shi, Wei
    Long, Jirong
    Guo, Xingyi
    Michailidou, Kyriaki
    Beesley, Jonathan
    Bolla, Manjeet K
    Shu, Xiao-Ou
    Lu, Yingchang
    Cai, Qiuyin
    Al-Ejeh, Fares
    Rozali, Esdy
    Wang, Qin
    Dennis, Joe
    Li, Bingshan
    Zeng, Chenjie
    Feng, Helian
    Gusev, Alexander
    Barfield, Richard T
    Andrulis, Irene L
    Anton-Culver, Hoda
    Arndt, Volker
    Aronson, Kristan J
    Auer, Paul L
    Barrdahl, Myrto
    Baynes, Caroline
    Beckmann, Matthias W
    Benitez, Javier
    Bermisheva, Marina
    Blomqvist, Carl
    Bogdanova, Natalia V
    Bojesen, Stig E
    Brauch, Hiltrud
    Brenner, Hermann
    Brinton, Louise
    Broberg, Per
    Brucker, Sara Y
    Burwinkel, Barbara
    Caldés, Trinidad
    Canzian, Federico
    Carter, Brian D
    Castelao, J Esteban
    Chang-Claude, Jenny
    Chen, Xiaoqing
    Cheng, Ting-Yuan David
    Christiansen, Hans
    Clarke, Christine L
    Collée, Margriet
    Cornelissen, Sten
    Couch, Fergus J
    Cox, David
    Cox, Angela
    Cross, Simon S
    Cunningham, Julie M
    Czene, Kamila
    Daly, Mary B
    Devilee, Peter
    Doheny, Kimberly F
    Dörk, Thilo
    Dos-Santos-Silva, Isabel
    Dumont, Martine
    Dwek, Miriam
    Eccles, Diana M
    Eilber, Ursula
    Eliassen, A Heather
    Engel, Christoph
    Eriksson, Mikael
    Fachal, Laura
    Fasching, Peter A
    Figueroa, Jonine
    Flesch-Janys, Dieter
    Fletcher, Olivia
    Flyger, Henrik
    Fritschi, Lin
    Gabrielson, Marike
    Gago-Dominguez, Manuela
    Gapstur, Susan M
    García-Closas, Montserrat
    Gaudet, Mia M
    Ghoussaini, Maya
    Giles, Graham G
    Goldberg, Mark S
    Goldgar, David E
    González-Neira, Anna
    Guénel, Pascal
    Hahnen, Eric
    Haiman, Christopher A
    Håkansson, Niclas
    Hall, Per
    Hallberg, Emily
    Hamann, Ute
    Harrington, Patricia
    Hein, Alexander
    Hicks, Belynda
    Hillemanns, Peter
    Hollestelle, Antoinette
    Hoover, Robert N
    Hopper, John L
    Huang, Guanmengqian
    Humphreys, Keith
    Hunter, David J
    Jakubowska, Anna
    Janni, Wolfgang
    John, Esther M
    Johnson, Nichola
    Jones, Kristine
    Jones, Michael E
    Jung, Audrey
    Kaaks, Rudolf
    Kerin, Michael J
    Khusnutdinova, Elza
    Kosma, Veli-Matti
    Kristensen, Vessela N
    Lambrechts, Diether
    Le Marchand, Loic
    Li, Jingmei
    Lindström, Sara
    Lissowska, Jolanta
    Lo, Wing-Yee
    Loibl, Sibylle
    Lubinski, Jan
    Luccarini, Craig
    Lux, Michael P
    MacInnis, Robert J
    Maishman, Tom
    Kostovska, Ivana Maleva
    Mannermaa, Arto
    Manson, JoAnn E
    Margolin, Sara
    Mavroudis, Dimitrios
    Meijers-Heijboer, Hanne
    Meindl, Alfons
    Menon, Usha
    Meyer, Jeffery
    Mulligan, Anna Marie
    Neuhausen, Susan L
    Nevanlinna, Heli
    Neven, Patrick
    Nielsen, Sune F
    Nordestgaard, Børge G
    Olopade, Olufunmilayo I
    Olson, Janet E
    Olsson, Håkan
    Peterlongo, Paolo
    Peto, Julian
    Plaseska-Karanfilska, Dijana
    Prentice, Ross
    Presneau, Nadege
    Pylkäs, Katri
    Rack, Brigitte
    Radice, Paolo
    Rahman, Nazneen
    Rennert, Gad
    Rennert, Hedy S
    Rhenius, Valerie
    Romero, Atocha
    Romm, Jane
    Rudolph, Anja
    Saloustros, Emmanouil
    Sandler, Dale P
    Sawyer, Elinor J
    Schmidt, Marjanka K
    Schmutzler, Rita K
    Schneeweiss, Andreas
    Scott, Rodney J
    Scott, Christopher G
    Seal, Sheila
    Shah, Mitul
    Shrubsole, Martha J
    Smeets, Ann
    Southey, Melissa C
    Spinelli, John J
    Stone, Jennifer
    Surowy, Harald
    Swerdlow, Anthony J
    Tamimi, Rulla M
    Tapper, William
    Taylor, Jack A
    Terry, Mary Beth
    Tessier, Daniel C
    Thomas, Abigail
    Thöne, Kathrin
    Tollenaar, Rob A E M
    Torres, Diana
    Truong, Thérèse
    Untch, Michael
    Vachon, Celine
    Van Den Berg, David
    Vincent, Daniel
    Waisfisz, Quinten
    Weinberg, Clarice R
    Wendt, Camilla
    Whittemore, Alice S
    Wildiers, Hans
    Willett, Walter C
    Winqvist, Robert
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Xia, Lucy
    Yang, Xiaohong R
    Ziogas, Argyrios
    Ziv, Elad
    Dunning, Alison M
    Pharoah, Paul D P
    Simard, Jacques
    Milne, Roger L
    Edwards, Stacey L
    Kraft, Peter
    Easton, Douglas F
    Chenevix-Trench, Georgia
    Zheng, Wei
    A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 7, p. 968-978Article in journal (Refereed)
    Abstract [en]

    , including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

  • 1161.
    Wärnberg, Fredrik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Prognosis in carcinoma in situ of the breast2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma.

    In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties.

    In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer.

    The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively.

    New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis.

    Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.

  • 1162.
    Wåhlin, Nils
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hydronephrosis in childhood: An experimental and clinical study2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis the pathophysiology of hydronephrosis due to ureteropelvic junction (UPJ) obstruction was studied. The kidney adapts to obstruction by changes in renal blood flow (RBF) and glomerular filtration rate (GFR). GFR is mainly regulated by the tubuloglomerular feedback (TGF) which acts as a negative feedback between the tubule and glomerular vessels.

    In earlier micropuncture experiments on rats with partial unilateral obstruction we have found an increase in TGF sensitivity during volume expansion (VE). It has also been shown that the degree of UPJ obstruction could be calculated using a pressure/flow (P/F) study technique.

    In a first series of experiments, the TGF response to VE in rats with bilateral partial obstruction was examined. A new balance between the kidneys occured, where the diuresis was greatest on the least obstructed side.

    The RBF was investigated by real transit time ultrasound in two studies. RBF was normal during basal conditions, but became significantly increased during VE in hydronephrotic animals. The response was thromboxane and/or nitric oxide dependent.

    In a last study, 44 patients with a diagnosis of hydronephrosis were examined with the P/F study technique prior to operation. It was shown that the outflow resistance of the UPJ could be accurately calculated in all cases.

    It is concluded that the normal adaptation of the kidney to obstruction depends on the presence of a normally functioning contralateral kidney. This adaptation includes a change of the filtration characteristics with is achieved through Tx and NO dependent vasodilatation and probably areduction of the filtration coefficient. It is further concluded that the degree of obstruction can be accurately calculated by a P/F study in patients with hydronephrosis.

  • 1163.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Department of surgery, Uppsala University Hospital, Uppsala, SE-75185, Sweden..
    Nelander, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ectopic pregnancy in simultaneous pancreas-kidney transplantation: A case report2016In: International journal of surgery case reports, ISSN 2210-2612, E-ISSN 2210-2612, Vol. 28, p. 152-154Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We present a case report of ectopic pregnancy (EP) after simultaneous pancreas-kidney transplantation (SKPTx). PRESENTATION OF CASE: A 33-year-old female status post SKPTx suddenly got abdominal pain in the lower level. She had high human chorionic Gonadotropin test. Ultrasonography revealed that there was no fetus in the uterus but a dilated right fallopian tube, which strongly suggested ectopic pregnancy. An emergency operation was performed and a dilated right side uterine tube was found with adhesions to her transplant. Salpingectomy was performed and no visible injury to the pancreas was found by the procedure. Pathological evaluation showed ectopic pregnant fetus, and no pancreas dysfunction was observed after the operation. DISCUSSION: This is the first case and operation report of EP after SKPTx. We should consider various causes of acute abdomen as well as several pathological condition in the transplanted pancreas such as pancreatitis, abscess, and thrombosis in vessels in the organ. Moreover, transplanted pancreas in abdomen is easily misrecognized as adipose tissue and there is high risk that the organ to get injured surgically. CONCLUSION: EP should be included in the different diagnosis in SKPTx female patients who get acute abdominal pain. It is highly desirable that transplant surgeon is included in the operation team for EP of these patients. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

  • 1164.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Univ Uppsala Hosp, Dept Surg, Div Transplantat, Uppsala, Sweden..
    Simultaneous Hand-Assisted Transperitoneal Bilateral Native Nephrectomy And Extracapsular Transplant Nephrectomy In A Patient With Polycystic Kidney Disease2015In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 216-216Article in journal (Other academic)
  • 1165. Yeung, C.K.
    et al.
    Barker, Gilian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Pathophysiology of Bladder dysfunction2010In: Pediatric Urology / [ed] John P. Gearhart, Richard C. Rink & Pierre D.E. Mouriqand, Philadelphia: Saunders/Elsevier , 2010, 2Chapter in book (Other academic)
  • 1166. Yngvesdotter, Linda
    et al.
    Huss, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Furebring, Mia
    EXCESSIVE DIURESIS DUE TO COLIMYCIN?2015Conference paper (Refereed)
  • 1167. Yngvesdotter, Linda
    et al.
    Huss, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Furebring, Mia
    Excessive diuresis due to Colimycin?2014Conference paper (Refereed)
  • 1168.
    Yonemura, Y.
    et al.
    Kusatsu Gen Hosp, Kishiwada Tokushukai Hosp, Peritoneal Surface Malignancy Ctr, Kishiwada, Shiga, Japan.;NPO Support Peritoneal Surface Malignancy Treatme, Osaka 6008189, Japan..
    Canbay, E.
    NPO Support Peritoneal Surface Malignancy Treatme, Osaka 6008189, Japan..
    Li, Y.
    Capital Med Univ, Beijin Shijitan Hosp, Dept Peritoneal Surface Oncol, Beijing 100038, Peoples R China..
    Coccolini, F.
    Gen Surg Papa Giovanni XXIII Hosp, Bergamo, Italy..
    Glehen, O.
    Univ Lyon, Ctr Hosp Lyon Sud, Dept Chirurg Gen, Hosp Civils Lyon, F-69495 Lyon, France..
    Sugarbaker, P. H.
    MedStar Washington Hosp Ctr, Ctr Gastrointestinal Malignancies, Program Peritoneal Surface Malignancies, Washington, DC 20010 USA..
    Morris, D.
    Univ New South Wales, St George Hosp, Dept Surg, Sydney, NSW 2052, Australia..
    Moran, B.
    Hampshire Hosp Fdn Trust, Peritoneal Malignancy Inst Basingstoke, Adelmaston Rd, Basingstoke RG24 9NA, Hants, England..
    Gonzaletz-Moreno, S.
    Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Peritoneal Surface Oncol Program, Madrid, Spain..
    Deraco, M.
    Natl Canc Inst, Milan, Italy..
    Piso, P.
    Univ Regensburg, Teaching Hosp, Krankenhaus Barmherzige Brieder, Regensburg, Germany..
    Elias, D.
    Inst Gustave Roussy, Dept Chirurg Gen, Villejuif, France..
    Batlett, D.
    Hillman Canc Ctr, Div Surg Oncol, 5115 Ctr Ave, Pittsburgh, PA 15232 USA..
    Ishibashi, H.
    Kusatsu Gen Hosp, Kishiwada Tokushukai Hosp, Peritoneal Surface Malignancy Ctr, Kishiwada, Shiga, Japan..
    Mizumoto, A.
    Kusatsu Gen Hosp, Kishiwada Tokushukai Hosp, Peritoneal Surface Malignancy Ctr, Kishiwada, Shiga, Japan..
    Verwaal, V.
    Ziekenhuis Eindhoven, Oncol GE Chirurg, Eindhoven, Netherlands..
    Mahtem, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    A comprehensive treatment for peritoneal metastases from gastric cancer with curative intent2016In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 8, p. 1123-1131Article, review/survey (Refereed)
    Abstract [en]

    Recently, Peritoneal Surface Oncology Group International (PSOGI) developed a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) for the treatment of peritoneal metastases (PM) from gastric cancer with curative intent. This article reviews the results of this treatment and verifies its indication. In this strategy, peritoneal cancer index (PCI) is determined by laparoscopy, and a peritoneal port is placed. Neoadjuvant bidirectional intraperitoneal/systemic chemotherapy (NIPS) is performed for 3 cycles, and then laparotomy is performed. Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemoperfusion (HIPEC) are performed. Multivariate analyses showed that completeness of cytoreduction, pathologic response to NIPS and PCI level and cytologic status after NIPS, as independent prognostic factors. PCI less than cut-off level after NIPS, negative cytology after NIPS, and positive response to NIPS were identified as the indications for comprehensive treatment. Patients who hold these criteria should be considered as the candidates for CRS and HIPEC.

  • 1169.
    Zabojova, Jorga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Thrikutam, Nikhitha
    Univ Texas Southwestern Med Ctr Dallas, Dept Plast & Reconstruct Surg, Dallas, TX 75390 USA.
    Tolley, Philip
    Univ Texas Southwestern Med Ctr Dallas, Dept Plast & Reconstruct Surg, Dallas, TX 75390 USA.
    Perez, Justin
    Univ Texas Southwestern Med Ctr Dallas, Dept Plast & Reconstruct Surg, Dallas, TX 75390 USA.
    Rozen, Shai M.
    Univ Texas Southwestern Med Ctr Dallas, Dept Plast & Reconstruct Surg, Dallas, TX 75390 USA.
    Rodriguez-Lorenzo, Andres
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Relational Anatomy of the Mimetic Muscles and Its Implications on Free Functional Muscle Inset in Facial Reanimation2018In: Annals of Plastic Surgery, ISSN 0148-7043, E-ISSN 1536-3708, Vol. 81, no 2, p. 203-207Article in journal (Refereed)
    Abstract [en]

    Background: The human smile is a complex coordinated activity of mimetic muscles predominantly recognizable by a superolateral pull at the commissure and elevation of the upper lip. The aim of this study was to revisit the muscles of facial expression responsible for these motions, evaluate their relational anatomy and orientation, and relate this to optimal positioning of free muscle transfer in smile reanimation.

    Methods: Nineteen hemifaces from fresh cadaveric specimens were dissected. A subsuperficial muscular aponeurotic system skin flap was elevated to expose the zygomaticus major, zygomaticus minor, levator labii superioris, and levator labii superioris alaeque nasi. Muscle location, length, width, angle of pull, and any anatomic variation were noted.

    Results: All specimens had zygomaticus major, levator labii superioris, and levator labii superioris alaeque nasi muscles present bilaterally. Conversely, the zygomaticus minor was present in only 10 of 19 hemifaces. There was no significant difference in muscle length, width, or line of pull between specimen sides. Of all the assessed muscles, the zygomaticus minor had the most transverse line of pull, at 31.6 degrees; the zygomaticus major was more oblique with a line of pull of 55.5 degrees; and the levator labii superioris and levator labii superioris alaeque nasi were oriented almost vertically with angles of 74.7 degrees and 79.0 degrees, respectively.

    Conclusions: The mimetic muscle vector is quite vertical in comparison to the angle obtained by traditional dynamic smile reconstruction surgeries. A more vertical vector, especially at the upper lip, should be considered in smile reconstruction.

  • 1170. Zedenius, Jan
    et al.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Endokrina organ2013In: Kirurgi / [ed] Hamberger, B och Haglund, U, Stockholm: Liber, 2013, 8, p. 383-416Chapter in book (Refereed)
  • 1171. Zelano, Johan
    et al.
    Berg, Alexander
    Thams, Sebastian
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cullheim, Staffan
    SynCAM1 expression correlates with restoration of central synapses on spinal motoneurons after two different models of peripheral nerve injury2009In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 517, no 5, p. 670-82Article in journal (Refereed)
    Abstract [en]

    SynCAM1 and neuroligins (NLGs) are adhesion molecules that govern synapse formation in vitro. In vivo, the molecules are expressed during synaptogenesis, and altered NLG function is linked to synapse dysfunction in autism. Less is known about SynCAM1 and NLGs in adult synapse remodeling. CNS synapse elimination occurs after peripheral nerve injury, which causes a transient decrease in synapse number on spinal motoneurons. Here we have studied the expression of SynCAM1 and NLGs in relation to changes in synaptic covering on spinal motoneurons. We performed sciatic nerve transection (SNT) or crush (SNC), axotomy models that result in poor or good conditions for axon regeneration, respectively. The two lesions resulted in similar synapse elimination and in poor (SNT) and good (SNC) return of synapses after 70 days. Functional recovery was good after SNC but absent after SNT. SynCAM1 mRNA decreased after 14 days in both models and was restored 70 days after SNC, but not after SNT. NLG2 and -3 mRNAs decreased to a smaller degree after SNC than after SNT. Synaptophysin immunoreactivity correlated with SynCAM1 mRNA 70 days after SNT and NLG2 mRNA 70 days after SNC. Surprisingly, an inverse correlation was seen between NLG3 mRNA and Vglut2, a marker for excitatory synapses, 70 days after SNT. We conclude that 1) SynCAM1 mRNA levels seem to reflect the loss and restoration of synapses on motoneurons, 2) down-regulation of NLGs is not a prerequisite for synapse elimination, and 3) expression of SynCAM1 and NLGs is regulated by different mechanisms during regeneration.

  • 1172.
    Zemgulis, Vitas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Energy-Related Metabolites during and after Induced Myocardial Ischemia and Retroperfusion of the Coronary Sinus: An Experimental Study in the Pig with the Microdialysis Technique and Extracorporeal Circulation2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischemic patients. The reasons for the absence of unambiguous results are not well understood nor are they scientifically explored. An experimental model was designed to mimic acute myocardial ischemia followed by extracorporeal circulation and reperfusion. This was accomplished with and without retroperfusion of the coronary sinus (RCS) during the period of vascular occlusion. Myocardial energy-related metabolites were monitored in open-chest pigs by microdialysis. The relationships between adenosine, taurine and nucleoside transport inhibition in ischemic myocardium are highlighted separately.

    Myocardial area at risk and infarct size were quantified.

    The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischemic myocardium. Of special interest was the unexpected finding of increased level of pyruvate in microdialysates of also non-ischemic myocardium. We have observed a preferentially anaerobic energy metabolism in potentially ischemic myocardium during continuous and pulsatile RCS, despite the alleviated effect of RCS as regards infarct size limitation.

    We found disturbances in energy-metabolism (studies without RCS) most probably due to a compromised function of the pyruvate dehydrogenase complex not only in ischemic but also in non-ischemic tissue during reperfusion. Even in presence of oxygen (studies with RCS-assist) the pattern of an aerobic production of lactate was obvious. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival. The overall net result of our studies on taurine transport suggests that taurine may represent an energy store of myocytes. This should be understood as a chemical intracellular gradient of taurine as a result of already performed osmotic work. This energy store could be exploited for Ca2+ extrusion to counteract Ca2+ overload and should be regarded as an equivalent to the high energy store of phosphocreatine.

  • 1173.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Clinical Studies in the Acute Phase of Subarachnoid Haemorrhage2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Patients admitted in similar clinical condition after spontaneous SAH can develop very different clinical courses. This could depend on the severity of the initial global ischemic brain injury at ictus. In the present study, we explored relations between clinical and radiological parameters at admission that indicate a more severe initial impact, and the following days hormone levels and brain metabolism.

    Early global cerebral oedema (GCE) on computed tomography occurred in 57 % of SAH patients and was associated with a more severe clinical condition. The brain’s glucose metabolism, measured with intracerebral microdialysis (MD), changed the first days. MD-glucose was initially high and MD-pyruvate low. MD-glucose gradually decreased and MD-pyruvate and MD-lactate increased, suggesting a transition to a hyperglycolytic state. This was more pronounced in patients with GCE. Similar patterns were seen for interstitial non-transmitter amino acids. From initial low concentrations, they gradually increased in parallel with MD-pyruvate. The amino acid concentrations were higher for patients admitted in better clinical condition. Insulin lowered MD-glucose and MD-pyruvate even when plasma glucose values remained high. P-ACTH and S-cortisol were elevated early after SAH. GCE was associated with higher S-cortisol acutely. Urine cortisol excretion, indicating levels of free cortisol, were higher in patients in a better clinical condition. Suppressed P-ACTH occurred in periods of brain ischemia.

    We suggest that GCE on the first CT scan is a warning sign indicating increased vulnerability if the patient is exposed to compromised energy supply or increased energy demand. Reduction of blood glucose after SAH should be done with caution. The temporal change of the glucose metabolism and the amino acid concentrations probably reflect activated repair mechanisms. This should be considered in the intensive care treatment of SAH patients. Finally, our results support earlier observations that the response of the hypothalamic-pituitary-adrenal system is important in critical care.

    List of papers
    1. Brain energy metabolism in patients with spontaneous subarachnoid hemorrhage and global cerebral edema
    Open this publication in new window or tab >>Brain energy metabolism in patients with spontaneous subarachnoid hemorrhage and global cerebral edema
    Show others...
    2010 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, no 6, p. 1102-1110Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Previous studies of spontaneous subarachnoid hemorrhage (SAH) have shown that global cerebral edema on the first computed tomography scan is associated with a more severe initial injury and is an independent predictor of poor outcome. Effects of secondary ischemic events also influence outcome after SAH. OBJECTIVE: This study demonstrates that early global edema is related to markers of an increased cerebral energy metabolism as measured with intracerebral microdialysis, which could increase vulnerability to adverse events. METHODS: Fifty-two patients with microdialysis monitoring after spontaneous SAH were stratified according to the occurrence of global cerebral edema on the first computed tomography scan taken a median of 2 hours after the initial bleed. Microdialysis levels of glucose, lactate, and pyruvate were compared between the global edema (n = 31) and no global edema (n = 21) groups. Clinical outcome was assessed with the Glasgow Outcome Scale score at >/= 6 months. RESULTS: Patients with global edema showed significantly elevated lactate and pyruvate levels 70 to 79 hours after SAH and marginally significantly higher levels of lactate 60 to 69 hours and 80 to 89 hours after SAH. There was a trend toward worse outcome in the edema group. CONCLUSION: Patients with global cerebral edema have higher interstitial levels of lactate and pyruvate. The edema group may have developed a cerebral hypermetabolism to meet the increased energy demand in the recovery phase after SAH. This stress would make the brain more vulnerable to secondary insults, increasing the likelihood of energy failure.

    Keywords
    Cerebral edema, Energy metabolism, Microdialysis, SAH
    National Category
    Medical and Health Sciences
    Research subject
    Neurosurgery
    Identifiers
    urn:nbn:se:uu:diva-128973 (URN)10.1227/01.NEU.0000370893.04586.73 (DOI)000278006200030 ()20495425 (PubMedID)
    Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
    2. Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage
    Open this publication in new window or tab >>Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage
    2010 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, no 9, p. 1527-1533Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Previous studies on spontaneous aneurysmal subarachnoid haemorrhage (SAH) treatment have found the presence of global cerebral oedema on the first CT scan to be a predictor of poor outcome. We have reviewed our own experience with SAH in order to evaluate the relation of global cerebral oedema to clinical parameters at admission and to functional outcome. METHODS: One hundred ninety patients with spontaneous aneurysmal SAH were included in the study. The first CT scan for each patient was evaluated for signs of global cerebral oedema. Clinical status on admission was assessed according to the Hunt & Hess score and the World Federation of Neurosurgical Societies (WFNS) grade and functional outcome using the Glasgow Outcome Scale (GOS). Clinical condition at admission was dichotomised as 'better' (Hunt & Hess 1-2, WFNS 1-2) or 'worse' (Hunt & Hess 3-5, WFNS 3-5) and outcome as 'favourable' (GOS 4-5) or 'poor' (GOS 1-3). The amount of blood on the CT scan was assessed using the Fisher scale. Comparisons were made between patients with and without global cerebral oedema on the first CT regarding clinical condition, age, gender, mode of aneurysm treatment, outcome, 6-month mortality, amount of blood on the CT scan and time lag to the first CT scan. RESULTS: Global cerebral oedema was observed in 57% of patients admitted with aneurysmal SAH, which is a much higher frequency than has been reported previously. Patients with oedema were admitted in a worse clinical status, but there was no difference between patients with and without oedema regarding other clinical parameters or outcome. The median time between the haemorrhage and the first CT scan was short compared to earlier studies, 2.5 h for those with oedema and 3.4 for those without. This difference was significant, suggesting that global cerebral oedema can be a very early phenomenon after SAH, and may be missed in later CT scans. Early global brain oedema, occurring within a few hours of bleeding, may be more common than previously thought. In aneurysmal SAH patients, the presence of global cerebral oedema was associated with a worse clinical condition at admission which in turn could indicate a more severe initial injury. The clinical significance of early oedema may differ from that of late oedema, which may explain the lack of an association between global oedema and poor outcome in this study. However, the nature of the oedema as well as its relation to the clinical course has to be further studied in separate studies.

    Keywords
    Subarachnoidal haemorrhage, Aneurysm, CT scan, Global brain oedema, Outcome
    National Category
    Surgery
    Research subject
    Neurosurgery
    Identifiers
    urn:nbn:se:uu:diva-128972 (URN)10.1007/s00701-010-0684-8 (DOI)000281246500011 ()20495834 (PubMedID)
    Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
    3. Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhage
    Open this publication in new window or tab >>Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhage
    Show others...
    (English)In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046XArticle in journal (Refereed) Submitted
    Abstract [en]

    Objective: An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimizing care in the acute phase of SAH.

    Patients: 55 patients with spontaneous SAH were evaluated regarding morning levels of S-Cortisol and P-ACTH seven days after the bleeding. In a subgroup of 20 patients the diurnal changes of S-Cortisol and P-ACTH levels were studied and U-Cortisol measured. The relations of hormone levels to clinical and radiological parameters and to outcome were assessed.

    Results: S-Cortisol and P-ACTH were elevated the day of SAH. S-Cortisol levels below reference range were uncommon. Early global cerebral oedema was associated with higher S-Cortisol concentrations at admission and a worse WFNS and RLS85 grade. Patients in better WFNS grade had higher U-Cortisol levels. All patients showed diurnal variations of S-Cortisol and P-ACTH. A reversed diurnal variation of S-Cortisol was more frequently seen in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-Cortisol peaks occurred especially in periods of secondary brain ischemia.

    Conclusion: There is a HPA response acutely after SAH with an increase of P-ACTH and S-Cortisol levels. Higher U-Cortisol levels in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-Cortisol levels at admission and may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischemia, indicating a possibly connection between brain ischemia and ACTH suppression. These two novel findings should be evaluated in further studies.

    Keywords
    Subarachnoid haemorrhage, Cortisol, ACTH, Diurnal variation, Cerebral oedema
    National Category
    Surgery
    Research subject
    Neurosurgery
    Identifiers
    urn:nbn:se:uu:diva-128968 (URN)
    Available from: 2010-08-04 Created: 2010-08-04 Last updated: 2017-12-12Bibliographically approved
    4. Temporal patterns of interstitial pyruvate and amino acids after subarachnoid haemorrhage are related to the level of consciousness: a clinical microdialysis study
    Open this publication in new window or tab >>Temporal patterns of interstitial pyruvate and amino acids after subarachnoid haemorrhage are related to the level of consciousness: a clinical microdialysis study
    Show others...
    2009 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, no 7, p. 771-780Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Temporal patterns of brain interstitial amino acids after subarachnoid haemorrhage (SAH) were studied in relation to energy metabolite levels and to the severity of the initial global ischaemia as reflected by the level of consciousness at admission. METHOD: Intracerebral microdialysis was used to measure brain interstitial amino acids and the energy metabolites glucose, lactate, and pyruvate during five days in 19 patients. Patients who were conscious (n = 11) were compared to those who were unconscious on admission (n = 8). FINDINGS: Eight non-transmitter amino acids (alanine, asparagine, glutamine, isoleucine, leucine, phenylalanine, serine and tyrosine), as well as glycine and pyruvate showed a pattern of increasing concentrations starting at 60-70 h after the onset of SAH. The conscious patients showed more pronounced elevations of non-transmitter amino acids, glycine, taurine and pyruvate compared to the unconscious patient group. Pyruvate levels were initially critically low for all patients, then normalised in the conscious patients but remained low in the unconscious group. CONCLUSIONS: There was an increase of the cerebral interstitial levels of non-transmitter amino acids and glycine which correlated temporally to pyruvate levels, more pronounced in patients conscious on admission. Pyruvate levels in these patients normalised, but remained reduced in the unconscious patients. The increase of the non-transmitter amino acids and glycine could reflect an increased amino acid turnover in an attempt at repairing the injured brain, which could have been hampered by the lower pyruvate levels. Interstitial pyruvate may be a useful marker of the energy metabolic situation in the acutely injured brain.

    Keywords
    amino acids, microdialysis, pyruvate, subarachnoid haemorrhage
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-107570 (URN)10.1007/s00701-009-0384-4 (DOI)000267388600007 ()19430719 (PubMedID)
    Available from: 2009-08-17 Created: 2009-08-17 Last updated: 2017-12-13Bibliographically approved
    5. Relation between brain interstitial and systemic glucose levels after subarachnoid hemorrhage
    Open this publication in new window or tab >>Relation between brain interstitial and systemic glucose levels after subarachnoid hemorrhage
    Show others...
    (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693Article in journal (Refereed) Submitted
    Abstract [en]

    Objects: The optimal blood glucose level after acute brain injury is not known. The aim of the present investigation was to study the relation between brain interstitial and systemic blood glucose levels during the acute phase after SAH. We also studied the effects of insulin administration on local brain energy metabolism.

    Methods: 19 patients with spontaneous SAH were monitored with intracerebral microdialysis (MD). The relation between plasma (P)-glucose and interstitial MD-glucose levels and the temporal pattern of MD-metabolites was studied seven days after SAH. With a target P-glucose of 5-10 mmol/L, the effect of insulin injection on brain energy metabolites (MD-glucose, lactate, pyruvate) and glutamate was evaluated.

    Results: The mean correlation coefficient between P-glucose and MD-glucose was 0.27 ± 0.27, (p=0.0005) with a high degree of individual variation. MD-glucose, MD/P-glucose ratio and MD-glutamate levels decreased in parallel with a gradual increase in MD-pyruvate and MD-lactate levels. There were no significant changes of MD-L/P ratio or MD-glycerol. Insulin administration induced a statistically significant decrease in MD-glucose and MD-pyruvate.

    Conclusion: After SAH, there was a positive correlation between P-glucose and MD-glucose levels with a high degree of individual variation. A gradual decline of MD-glucose and MD/P-glucose ratio and an increase of MD-pyruvate and MD-lactate levels during the first week after SAH could suggest a transition to a hyperglycolytic state with increased cerebral glucose consumption. Administration of insulin was related to lowering of MD-glucose and MD-pyruvate, often to critically low levels even though plasma glucose values remained above 6 mmol/L. Thus, P-glucose should not be low in the acute phase after SAH and administration of insulin should be done with caution, even more crucial when the cerebral glucose metabolism has recovered and an increased energy demand is developing in the injured, repairing brain.

    Keywords
    Brain glucose, Blood glucose, Insulin, Microdialysis, Subarachnoid hemorrhage
    National Category
    Surgery
    Research subject
    Neurosurgery
    Identifiers
    urn:nbn:se:uu:diva-128970 (URN)
    Available from: 2010-08-04 Created: 2010-08-04 Last updated: 2017-12-12Bibliographically approved
  • 1174.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Regarding "Somatotropic and thyroid hormones in the acute phase of subarachnoid hemorrhage"2014In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 156, no 5, p. 977-977Article in journal (Other academic)
  • 1175.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Hallberg, Lena
    Department of Radiology, Karolinska University Hospital, Huddinge.
    Hillered, Lars
    Uppsala University. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ronne Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhageIn: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046XArticle in journal (Refereed)
    Abstract [en]

    Objective: An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimizing care in the acute phase of SAH.

    Patients: 55 patients with spontaneous SAH were evaluated regarding morning levels of S-Cortisol and P-ACTH seven days after the bleeding. In a subgroup of 20 patients the diurnal changes of S-Cortisol and P-ACTH levels were studied and U-Cortisol measured. The relations of hormone levels to clinical and radiological parameters and to outcome were assessed.

    Results: S-Cortisol and P-ACTH were elevated the day of SAH. S-Cortisol levels below reference range were uncommon. Early global cerebral oedema was associated with higher S-Cortisol concentrations at admission and a worse WFNS and RLS85 grade. Patients in better WFNS grade had higher U-Cortisol levels. All patients showed diurnal variations of S-Cortisol and P-ACTH. A reversed diurnal variation of S-Cortisol was more frequently seen in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-Cortisol peaks occurred especially in periods of secondary brain ischemia.

    Conclusion: There is a HPA response acutely after SAH with an increase of P-ACTH and S-Cortisol levels. Higher U-Cortisol levels in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-Cortisol levels at admission and may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischemia, indicating a possibly connection between brain ischemia and ACTH suppression. These two novel findings should be evaluated in further studies.

  • 1176.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hallberg, Lena
    Department of Radiology Karolinska University Hospital, Huddinge.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage2010In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, no 9, p. 1527-1533Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies on spontaneous aneurysmal subarachnoid haemorrhage (SAH) treatment have found the presence of global cerebral oedema on the first CT scan to be a predictor of poor outcome. We have reviewed our own experience with SAH in order to evaluate the relation of global cerebral oedema to clinical parameters at admission and to functional outcome. METHODS: One hundred ninety patients with spontaneous aneurysmal SAH were included in the study. The first CT scan for each patient was evaluated for signs of global cerebral oedema. Clinical status on admission was assessed according to the Hunt & Hess score and the World Federation of Neurosurgical Societies (WFNS) grade and functional outcome using the Glasgow Outcome Scale (GOS). Clinical condition at admission was dichotomised as 'better' (Hunt & Hess 1-2, WFNS 1-2) or 'worse' (Hunt & Hess 3-5, WFNS 3-5) and outcome as 'favourable' (GOS 4-5) or 'poor' (GOS 1-3). The amount of blood on the CT scan was assessed using the Fisher scale. Comparisons were made between patients with and without global cerebral oedema on the first CT regarding clinical condition, age, gender, mode of aneurysm treatment, outcome, 6-month mortality, amount of blood on the CT scan and time lag to the first CT scan. RESULTS: Global cerebral oedema was observed in 57% of patients admitted with aneurysmal SAH, which is a much higher frequency than has been reported previously. Patients with oedema were admitted in a worse clinical status, but there was no difference between patients with and without oedema regarding other clinical parameters or outcome. The median time between the haemorrhage and the first CT scan was short compared to earlier studies, 2.5 h for those with oedema and 3.4 for those without. This difference was significant, suggesting that global cerebral oedema can be a very early phenomenon after SAH, and may be missed in later CT scans. Early global brain oedema, occurring within a few hours of bleeding, may be more common than previously thought. In aneurysmal SAH patients, the presence of global cerebral oedema was associated with a worse clinical condition at admission which in turn could indicate a more severe initial injury. The clinical significance of early oedema may differ from that of late oedema, which may explain the lack of an association between global oedema and poor outcome in this study. However, the nature of the oedema as well as its relation to the clinical course has to be further studied in separate studies.

  • 1177.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ronne Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Relation between brain interstitial and systemic glucose levels after subarachnoid hemorrhageIn: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693Article in journal (Refereed)
    Abstract [en]

    Objects: The optimal blood glucose level after acute brain injury is not known. The aim of the present investigation was to study the relation between brain interstitial and systemic blood glucose levels during the acute phase after SAH. We also studied the effects of insulin administration on local brain energy metabolism.

    Methods: 19 patients with spontaneous SAH were monitored with intracerebral microdialysis (MD). The relation between plasma (P)-glucose and interstitial MD-glucose levels and the temporal pattern of MD-metabolites was studied seven days after SAH. With a target P-glucose of 5-10 mmol/L, the effect of insulin injection on brain energy metabolites (MD-glucose, lactate, pyruvate) and glutamate was evaluated.

    Results: The mean correlation coefficient between P-glucose and MD-glucose was 0.27 ± 0.27, (p=0.0005) with a high degree of individual variation. MD-glucose, MD/P-glucose ratio and MD-glutamate levels decreased in parallel with a gradual increase in MD-pyruvate and MD-lactate levels. There were no significant changes of MD-L/P ratio or MD-glycerol. Insulin administration induced a statistically significant decrease in MD-glucose and MD-pyruvate.

    Conclusion: After SAH, there was a positive correlation between P-glucose and MD-glucose levels with a high degree of individual variation. A gradual decline of MD-glucose and MD/P-glucose ratio and an increase of MD-pyruvate and MD-lactate levels during the first week after SAH could suggest a transition to a hyperglycolytic state with increased cerebral glucose consumption. Administration of insulin was related to lowering of MD-glucose and MD-pyruvate, often to critically low levels even though plasma glucose values remained above 6 mmol/L. Thus, P-glucose should not be low in the acute phase after SAH and administration of insulin should be done with caution, even more crucial when the cerebral glucose metabolism has recovered and an increased energy demand is developing in the injured, repairing brain.

  • 1178.
    Zetterström, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Artursson, Gösta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Plasma oncotic pressure and plasma protein concentration in patients following thermal injury1980In: Acta Anaesthesiologica Scandinavica, ISSN ISSN 0001-5172, Vol. 24, p. 288-294Article in journal (Refereed)
  • 1179.
    Zhang, Rong
    et al.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Knapp, Michael
    Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany..
    Suzuki, Kentaro
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Kajioka, Daiki
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Schmidt, Johanna M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Inst Anat, Bonn, Germany..
    Winkler, Jonas
    Univ Bonn, Inst Anat, Bonn, Germany..
    Yilmaz, Oeznur
    Univ Bonn, Inst Anat, Bonn, Germany..
    Pleschka, Michael
    Univ Bonn, Inst Anat, Bonn, Germany..
    Cao, Jia
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Kockum, Christina Clementson
    Univ Lund Hosp, Dept Pediat Surg, Lund, Sweden..
    Barker, Gillian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Holmdahl, Gundela
    Queen Silvias Childrens Hosp, Dept Pediat Surg, Gothenburg, Sweden..
    Beaman, Glenda
    Univ Manchester, Ctr Genom Med, Manchester M13 9PL, Lancs, England..
    Keene, David
    Woolf, Adrian S.
    Univ Manchester, Manchester Acad Hlth Sci, Inst Human Dev, Manchester M13 9PL, Lancs, England.;Royal Manchester Childrens Hosp, Manchester, Lancs, England..
    Cervellione, Raimondo M.
    Cent Manchester Univ Hosp NHS Fdn Trust, Royal Manchester Childrens Hosp, Paediat Urol, Manchester, Lancs, England..
    Cheng, Wei
    Capital Inst Pediat, Dept Pediat Surg, Beijing, Peoples R China.;Monash Univ, Fac Med Nursing & Hlth Sci, Southern Med Sch, Dept Paediat, Clayton, Vic, Australia.;Monash Univ, Fac Med Nursing & Hlth Sci, Southern Med Sch, Dept Surg, Clayton, Vic, Australia.;Beijing United Family Hosp, Dept Surg, Beijing, Peoples R China..
    Wilkins, Simon
    Cabrini Monash Univ, Cabrini Hosp, Dept Surg, Melbourne, Vic, Australia.;Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Clayton, Vic 3800, Australia..
    Gearhart, John P.
    Johns Hopkins Sch Med, Div Pediat Urol, Baltimore, MD USA..
    Sirchia, Fabio
    Univ Torino, Citta Salute & Sci Univ Hosp, Dept Med Sci, Turin, Italy.;Univ Torino, Citta Salute & Sci Univ Hosp, Med Genet Unit, Turin, Italy..
    Di Grazia, Massimo
    IRCCS Burlo Garofalo, Inst Maternal & Child Hlth, Trieste, Italy..
    Ebert, Anne-Karolin
    Univ Hosp Ulm, Dept Urol & Pediat Urol, Ulm, Germany..
    Roesch, Wolfgang
    St Hedwig Hosp Barmherzige Bruder, Dept Pediat Urol, Regensburg, Germany..
    Ellinger, Joerg
    Univ Hosp Bonn, Dept Urol, Bonn, Germany..
    Jenetzky, Ekkehart
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;Johannes Gutenberg Univ Mainz, Dept Child & Adolescent Psychiat & Psychotherapy, Mainz, Germany..
    Zwink, Nadine
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Feitz, Wout F.
    Radboud Univ Nijmegen, Med Ctr, Pediat Urol Ctr, Dept Urol, Nijmegen, Netherlands..
    Marcelis, Carlo
    Radboud Univ Nijmegen, Med Ctr, Dept Genet, Nijmegen, Netherlands..
    Schumacher, Johannes
    Univ Bonn, Inst Human Genet, Bonn, Germany..
    Martinon-Torres, Federico
    Hosp Clin Univ Santiago, Translat Pediat & Infect Dis, Santiago De Compostela, Spain.;Inst Invest Sanitaria Santiago Santiago, GENVIP Res Grp Www Genvip Org, Galicia, Spain..
    Hibberd, Martin Lloyd
    Genome Inst Singapore, Singapore, Singapore..
    Khor, Chiea Chuen
    Univ Calif Davis, Med Ctr, Dept Pediat, Div Genom Med, Sacramento, CA 95817 USA..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Barth, Sandra
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Boyadjiev, Simeon A.
    Univ Calif Davis, Med Ctr, Dept Pediat, Div Genom Med, Sacramento, CA 95817 USA..
    Brusco, Alfredo
    Univ Torino, Citta Salute & Sci Univ Hosp, Dept Med Sci, Turin, Italy.;Univ Torino, Citta Salute & Sci Univ Hosp, Med Genet Unit, Turin, Italy..
    Ludwig, Michael
    Univ Bonn, Dept Clin Chem & Clin Pharmacol, Bonn, Germany..
    Newman, William
    Univ Manchester, Ctr Genom Med, Manchester M13 9PL, Lancs, England..
    Nordenskjold, Agneta
    Karolinska Univ Hosp, Astrid Lindgren Children Hosp, Pediat Surg, Stockholm, Sweden..
    Yamada, Gen
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Odermatt, Benjamin
    Univ Bonn, Inst Anat, Bonn, Germany..
    Reutter, Heiko
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Childrens Hosp, Dept Neonatol & Pediat Intens Care, Bonn, Germany.;Univ Bonn, Bonn, Germany..
    ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42170Article in journal (Refereed)
    Abstract [en]

    Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

  • 1180. Zoerner, Frank
    et al.
    Semenas, Egidijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Resuscitation with amiodarone increases survival after hemorrhage and ventricular fibrillation in pigs2014In: Journal of Trauma and Acute Care Surgery, ISSN 2163-0755, Vol. 76, no 6, p. 1402-1408Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this experimental study was to compare survival and hemodynamic effects of a low-dose amiodarone and vasopressin compared with vasopressin in hypovolemic cardiac arrest model in piglets. METHODS: Eighteen anesthetized male piglets (with a weight of 25.3 [1.8] kg) were bled approximately 30% of the total blood volume via the femoral artery to a mean arterial blood pressure of 35 mm Hg in a 15-minute period. Afterward, the piglets were subjected to 4 minutes of untreated ventricular fibrillation followed by 11 minutes of open-chest cardiopulmonary resuscitation. At 5 minutes, circulatory arrest amiodarone 1 mg/kg was intravenously administered in the amiodarone group (n = 9), while the control group received the same amount of saline (n = 9). At the same time, all piglets received vasopressin 0.4 U/kg intravenously administered and hypertonic-hyperoncotic solution 3-mL/kg infusion for 20 minutes. Internal defibrillation was attempted from 7 minutes of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 hours after resuscitation. RESULTS: Three-hour survival was greater in the amiodarone group (p = 0.02). After the successful resuscitation, the amiodarone group piglets had significantly lower heart rate as well as greater systolic, diastolic, and mean arterial pressure. Troponin I plasma concentrations were lower and urine output was greater in the amiodarone group. CONCLUSION: Combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters, and smaller myocardial injury compared with resuscitation with vasopressin only.

  • 1181.
    Åberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pankotai, Eszter
    Weszl, Miklós
    Forster-Horváth, Casba
    Hulsart Billström, Gry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lacza, Zombor
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vivo evaluation of an injectable premixed radiopaque calcium phosphate cement2011In: EFORT, 2011Conference paper (Refereed)
  • 1182.
    Åberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Hulsart Billström, Gry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Brisby, Helena
    Thomsen, Peter
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Evaluation of a radio-opaque premixed calcium phosphate cement2010In: Scandinavian Society or Biomaterials Annual Meeting, 2010Conference paper (Refereed)
  • 1183.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Leo Swenne, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Elective orthopedic and cardiopulmonary bypass surgery causes a reduction in serum endostatin levels2014In: European Journal of Medical Research, ISSN 0949-2321, E-ISSN 2047-783X, Vol. 19, p. 61-Article in journal (Refereed)
    Abstract [en]

    Background: Endostatin is an endogenous inhibitor of angiogenesis that inhibits neovascularisation. The aim of the study was to evaluate the effect of elective surgery on endostatin levels.

    Methods: Blood samples were collected prior to elective surgery and 4 and 30 days postoperatively in 2 patient groups: orthopedic surgery (n =27) and coronary bypass patients (n =21). Serum endostatin levels were measured by ELISA.

    Results: Serum endostatin was significantly reduced 30 days after surgery in comparison with presurgical values in both the orthopedic (P =0.03) and cardiopulmonary surgery (P =0.04) group.

    Conclusion: Serum endostatin is reduced 30 days after surgery. This reduction would favor angiogenesis and wound-healing.

  • 1184.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Circulating Human Fractalkine is Decreased Post-operatively After Orthopedic and Coronary Bypass Surgery2014In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 28, no 2, p. 185-188Article in journal (Refereed)
    Abstract [en]

    Fractalkine is an important chemokine involved in resolving normal inflammatory processes such as wound healing. Soluble fractalkine acts as a chemoattractant bringing cytotoxic and cytokine-producing cells to areas of inflammation. The aim of the present study was to investigate circulating fractalkine during inflammatory response induced by surgery.

    MATERIALS AND METHODS: Fractalkine was analyzed in serum samples from orthopedic surgery patients (n=29) and coronary bypass patients (n=21). The samples were collected prior to surgery and 4 and 30 days after surgery, respectively.

    RESULTS: Fractalkine concentrations decreased from pre-operative levels of 1,764 (1,330-2,434) pg/mL to 1,520 (1,330-2,434) pg/mL at 4 days after surgery, and to 1,285 (1,099-1,462) pg/mL 30 days after surgery in patients undergoing orthopedic procedures (p<0.01, 30 days post-operatively versus pre-operatively). Furthermore, fractalkine concentrations decreased significantly from pre-operative levels of 1,856 (1,520-2,434) pg/mL to 1,338 (964-1,650) pg/mL 4 days post-operatively and to 1,266 (1,080-1,338) pg/mL 30 days post-operatively in patients undergoing coronary bypass surgery (p<0.01, 30 days post-operative versus pre-operative values).

    CONCLUSION: A significant and persistent decrease in circulating fractalkine was observed after orthopedic and coronary bypass surgery despite a marked inflammatory response.

  • 1185.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Introduction to symposium: "New genetics with impact on treatment of endocrine tumour disease"2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 536-539Article in journal (Other academic)
    Abstract [en]

    Read more articles from the symposium: Endocrine tumors - new generation sequencing with impact on therapy.

  • 1186.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Natural History of untreated primary hyperparathyroidism2016In: Textbook of Endocrine Surgery: / [ed] Dr. Orlo H Clark MD, Dr. Quan-Yang Duh MD, Dr. Electron Kebebew MD, Dr. Jessica E Gosnell MD and Dr. Wen T Shen MA MD, Jaypee Brothers Medical Publishers , 2016, 3Chapter in book (Refereed)
  • 1187.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Resection of Small intestinal neuroendocrine tumors2016In: Atlas of endocrine surgical techniques / [ed] Sally E Carty, Jaypee Brothers Medical Publishers , 2016Chapter in book (Refereed)
  • 1188.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Remedial Parathyroid Surgery2012In: Surgery of the Thyroid and Parathyroid Glands / [ed] D. Oertli, R. Udelsman, Springer Berlin/Heidelberg, 2012, 2, p. 555-577Chapter in book (Refereed)
  • 1189.
    Åkerström, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Multiple Endocrine Neoplasia type 22018In: Textbook of Complex General Surgical Oncology / [ed] Shane Y Morita, Charles M Balch, V. Suzanne Klimberg, Timothy M. Pawlik, Mitchell C. Posner, Kenneth K. Tanabe, McGraw-Hill, 2018Chapter in book (Refereed)
  • 1190.
    Åkesson, Marlene
    et al.
    Uppsala University, Interfaculty Units, Centrum för klinisk forskning, Gävleborg.
    Rahm, Vivi-Anne
    Uppsala University, Interfaculty Units, Centrum för klinisk forskning, Gävleborg.
    Näringsdryck sju dagar före planerad operation: effekter på det pre- och postoperativa förloppet för tarmkirurgipatienter2005Report (Other (popular scientific, debate etc.))
    Abstract [en]

    Introduction: During the last decades, the contribution of good nutrition to better results in health care has been emphasised.

    Aim: To investigate if a nutritional drink, given seven days before a planned operation to patients undergoing intestinal surgery, can influence the degree of malnutrition and insulin resistance and thereby consequences in the pre and postoperative phases, as compared to when patients did not receive the nutritional drink.

    Method: En randomised controlled trial. The data collected using two instruments, a diary together with protocols and a blood test. All together there were 24 patients in the intervention group and 22 patients in the control group.

    Results: Pre and postoperative nausea were significantly lower in the intervention group. Nutrition status, assessed as transtyretin values, declined from the point of inclusion to the day of operation in both groups but twice as much in the control group, despite that the latter were more postoperatively more insulin resistance. In the intervention group, clinically postoperative effects could be seen in terms of mobilisation, feelings of well-being, complications and earlier gas releases. There were no clinically or statistically significant differences in length of care or nutrition.

    Conclusions: A nutritional drink seven days prior to planned surgery had a positive effect on the pre and postoperative condition of the patients. The study can help the health care personal to realise the importance of patients being well nourished prior to intestinal surgery

    which will in turn be of benefit to the patients.

  • 1191.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Medical Therapy of Gastrointestinal Neuroendocrine Tumors2017In: Visceral Medicine, ISSN 2297-4725, Vol. 33, no 5, p. 352-356Article, review/survey (Refereed)
    Abstract [en]

    Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium177-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.

  • 1192.
    Öhnstedt, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Ilya Pharma AB, Dag Hammarskiolds Vag, Uppsala, Sweden.
    Lofton Tomenius, Hava
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Ilya Pharma AB, Dag Hammarskiolds Vag, Uppsala, Sweden.
    Vågesjö, Evelina
    Ilya Pharma AB, Dag Hammarskiolds Vag, Uppsala, Sweden.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Ilya Pharma AB, Dag Hammarskiolds Vag, Uppsala, Sweden.
    The discovery and development of topical medicines for wound healing2019In: Expert Opinion on Drug Discovery, ISSN 1746-0441, E-ISSN 1746-045X, Vol. 14, no 5, p. 485-497Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Chronic, nonhealing skin wounds claim >3% of the health-care budget in industrialized countries, and the incidence is rising. Currently, two parallel trends influence innovations within the field of wound healing: the need to reduce spread of antibiotic resistance and the emerging use of health economy and value-based models.Areas covered: This review focuses on the discovery of drug candidates and development of treatments aiming to enhance wound healing in the heterogeneous group of patients with nonhealing wounds.Expert opinion: Nonhealing wounds are multifaceted and recognized as difficult indications. The majority of products currently in use are medical device dressings, or concepts of negative pressure or hyperbaric oxygen treatment. Global best practice guidelines for the treatment of diabetic foot ulcers recommend debridement, redressing, as well as infection control, and are critical to the lack of coherent clinical evidence for many approved products in active wound care. To accelerate wound healing, there is an emerging trend toward biologics, gene therapy, and novel concepts for drug delivery in research and in the pipeline for clinical trials. Scientific delineation of the therapeutic mechanism of action is, in our opinion, vital for clinical trial success and for an increased fraction of medical products in the pharmaceutical pipeline.

  • 1193.
    Öhrvall, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Intraoperative scintigraphic detection of abdominal endocrine tumors: Development and evaluation of hand held gamma sensitive probes for¹¹¹In1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Surgery of endocrine tumors benefit from accurate pre and- intraoperative localization methods,and scintigraphy has become an important contribution in this respect. In the present thesis therequisites for scintigraphic localization of abdominal endocrine tumors and new detectors forintraoperative gammadetection are evaluated.

    Ac5 is a monoclonal murine antibody developed against human adrenocortical carcinoma. In a nude mouse experimental model, the radiolabeled antibody and its Fab´2 fragment were evaluated after grafting of two human adrenocortical carcinoma cell-lines (SW 13, T-CAR1). During scintigraphy of grafted animals, tumors were visualized especially with the fragmented antibody. The Ac5 antibody/Fab2 fragment may become a diagnostic tool for detection of adrenocortical carcinoma.

    The somatostatin analogue [111In]-DTPA-D-[Phe1]-octreotide (OctreoScan®) has been shown to visualize endocrine tumors with scintigraphy. The biodistribution of [111In]-DTPA-D-[phe1]-octreotide was studied by use of operative biopsies. Mid-gut carcinoids and endocrine pancreatic tumors of patients exposed to [111In]-DTPA-D-[Phe1]-octreotide, revealed high uptake in tumors with a tumor-to-blood ratio up to 2000. After preoperative single photon emission computerized tomography (SPECT), commercially available hand-held gammasensitive probes were used for intraoperative detection of tumors. These detectors were found to be insufficient in the abdomen mainly because of poor adaptation to the high background activity of 111In. A novel detector, H-probe2 was constructed. It was found to detect even tiny tumors, lesions inaccessible to surgical palpation upon ex vivo scanning of operative specimens. In vivo, H-probe2 detected smaller tumors than preoperative SPECT, but the scanning procedure was too time consuming for surgical applicability. Further development resulted in Matris 16, a computerized 16 channel detector for intraoperative use in combination with [111In]-DTPA-D-[Phe1]-octreotide. Matris 16 demonstratedsubstantial sensitivity and spatial resolution. It had the ability to detect abdominal endocrine tumorsmeasuring down to a few mm both in vivo and ex vivo. By allowing faster scanning with preserved sensitivity Matris 16 can improve the intraoperative tumor detection of endocrine neoplasms.

  • 1194.
    Österberg, Asbjörn
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Faecal incontinence: Aspects of diagnosis and treatment1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rectal reservoir function and anal pressures were investigated using anorectal manovolumetry in 48 patients with faecal incontinence and in 25 control subjects. Resting and squeeze pressures were lower in patients (p<0.001), but no significant difference was seen concerning rectal sensibility or compliance. The primary defect in incontinent patients seems to be a sphincter dysfunction. Any reduction in rectal compliance is likely to be a secondary phenomenon.

    The longitudinal high pressure zone profile was evaluated in 156 patients and 25 healthy controls using anorectal manometry with a station pull-through technique, 1 to 6 cm from the anal verge. Resting and squeeze pressures were lower in patients (P<0.01-0.001) apart from the proximal half of the measured length during rest. The high pressure zone was shorter in patients (P<0.05). There was a more proximal pressure accumulation in patients at rest (P<0.05). The main difference between incontinent patients and controls was a greater magnitude of the pressure profile in the latter group.

    Results of neurophysiological investigation (pudendal nerve terminal motor latency (PNTML) and fibre density (FD)) were studied prospectively in 72 patients with faecal incontinence. Prolonged PNTML was found in 46% and increased FD in 82% of the patients. FD but not PNTML was correlated to clinical and manometric variables.

    A questionnaire used in the assessment of patients with faecal incontinence and constipation was evaluated prospectively for 36 patients with incontinence and 38 with constipation. Reliability and validity were judged acceptable. Faecal incontinence per se was reproducible, as was the need to wear a pad. Several items distinguished both patient groups from healthy controls (P<0.05-0.001).

    Effects of electrostimulation of the pelvic floor were studied in 24 patients with idiopathic (neurogenic) incontinence. The results were evaluated at 3 and 12 months with a questionnaire and anorectal manometry. Eleven patients (46%) reported improvement after 3 months, and 9 (38%) after one year. Variables reflecting sphincter competence did not improve.

    Functional results of anterior levatorplasty (n=31) and sphincteroplasty (n=20) for idiopathic incontinence or sphincter injury were evaluated at 3 and 12 months. Eighteen patients (58%) in the levatorplasty group reported continence to solid and loose stools after one year, as compared with two patients (6%) before surgery (P<0.01). The corresponding figures in the sphincteroplasty group were 50% and 11% (P<0.05). Improvements were also observed concerning social and physical handicap in both groups.

    In a randomised trial, the results of levatorplasty (n=33) were compared with electrostimulation (n=29) for idiopathic (neurogenic) faecal incontinence. Improved incontinence scores after 3 months were seen in 29 patients (88%) after levatorplasty compared with 19 patients (66%) after electrostimulation (P<0.05). Improvements concerning deferring time for stool and social and physical handicap were more pronounced after levatorplasty.

  • 1195.
    Österberg, Johanna
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice: Clinical and Experimental Studies with Special Emphasis on the Cellular Immune Response2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Patients with peritonitis or malignant obstructive jaundice (HPB+) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs.

    BT occurred infrequently in patients with acute peritonitis and in HPB+ there was no evidence of BT. Peritonitis and HPB+ causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB+ a high rate of apoptosis in MLNs was observed.

    An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB+. Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.

    List of papers
    1. Alteration in mucosal immune cell distribution in septic rats
    Open this publication in new window or tab >>Alteration in mucosal immune cell distribution in septic rats
    Show others...
    1997 In: Shock, ISSN 1073-2322, Vol. 7, no 3, p. 182-185.Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92553 (URN)
    Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
    2. Effect of Linomide on gut immune cell distribution and on TNF-α in plasma and ascites:an experimental study in the septic rat
    Open this publication in new window or tab >>Effect of Linomide on gut immune cell distribution and on TNF-α in plasma and ascites:an experimental study in the septic rat
    2002 In: Shock, ISSN 1073-2322, Vol. 18, no 5, p. 471-475Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92554 (URN)
    Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
    3. Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis
    Open this publication in new window or tab >>Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-92555 (URN)
    Available from: 2005-02-17 Created: 2005-02-17 Last updated: 2010-01-13Bibliographically approved
    4. Microbial translocation and inflammatory response in patients with acute peritonitis
    Open this publication in new window or tab >>Microbial translocation and inflammatory response in patients with acute peritonitis
    Show others...
    2004 In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 39, no 7, p. 657-664Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92556 (URN)
    Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
    5. Inflammatory response in patients with malignant obstructive jaundice
    Open this publication in new window or tab >>Inflammatory response in patients with malignant obstructive jaundice
    Show others...
    2007 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 1, p. 94-102Article in journal (Refereed) Published
    Abstract [en]

    Objective. Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract. Material and methods. Patients with obstructive jaundice (group HPB+) were compared with those without (HPB-). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-α, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis). Results. Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB+. The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased. Conclusions. Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.

    Keywords
    Apoptosis, bacterial translocation, cytokines, endotoxins, lymphocytes, obstructive jaundice, surgery
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-92557 (URN)10.1080/00365520600825190 (DOI)000243724800016 ()17190769 (PubMedID)
    Available from: 2005-02-17 Created: 2005-02-17 Last updated: 2017-12-14Bibliographically approved
  • 1196.
    Östman, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Influence of Oxidative Stress on Muscle and Bone2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Reactive oxygen species (ROS) induce oxidative stress and although are primarily recognized for playing a deleterious biological role, they can be beneficial to cell systems. ROS are extremely short-lived and normally tightly regulated by antioxidant defence systems. Cells react to oxidative stress in different ways, which primarily depends on cell type, stress severity, or both. There is a general limitation in extrapolating to humans conclusions drawn from in vitro and animal studies because of important species-specific differences. Therefore, the general aim of this thesis was to study the influence of oxidative stress on human muscle and bone in vivo.

    In paper I we presented a one-step HPLC method optimized for the simultaneous determination of purine degradation products in small microdialysis samples. The clinical utility of the method was successfully tested in a patient with traumatic brain injury. In paper II we evaluated microdialysis as an in vivo method to characterize the relative kinetics of ROS-related metabolites in human skeletal muscle exposed to ischaemia-reperfusion. Results indicated that microdialysis was feasible and safe to use in monitoring metabolic events during tourniquet-assisted surgery. In paper III we investigated the association between an oxidative stress marker (urinary 8-iso-PGF) and bone mineral density (BMD) and whether α-tocopherol modified the association. The main finding was the negative association between 8-iso-PGF and BMD and that the association was further dependent on serum α-tocopherol level. In paper IV we performed a randomized controlled trial to evaluate the influence of Q10 supplementation on exercise performance and metabolites of muscular damage. We did not observe any effects on exercise capacity after 8 weeks of Q10 administration. Nor did we find a significant effect on serum markers related to oxidative stress.

    In conclusion we have studied the influence of oxidative stress on muscle and bone in vivo in humans. The oxidative stress was triggered by four different causes (trauma, ischemia-reperfusion, ageing, and exercise exhaustion).

    List of papers
    1. Hypoxanthine, uric acid and allantoin as indicators of in vivo free radical reactions. Description of a HPLC method and human brain microdialysis data.
    Open this publication in new window or tab >>Hypoxanthine, uric acid and allantoin as indicators of in vivo free radical reactions. Description of a HPLC method and human brain microdialysis data.
    Show others...
    2000 (English)In: Acta Neurochir (Wien), Vol. 142Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-56099 (URN)
    Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-01-14
    2. Tourniquet-induced ischemia and reperfusion in human skeletal muscle
    Open this publication in new window or tab >>Tourniquet-induced ischemia and reperfusion in human skeletal muscle
    2004 (English)In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 418, p. 260-265Article in journal (Refereed) Published
    Abstract [en]

    Microdialysis conceivably enables longitudinal and simultaneous investigation of several metabolites by repeated measurements in skeletal muscle. We used and evaluated microdialysis as an in vivo method to characterize the time-course and relative kinetics of pyruvate, glucose, lactate, glycerol, hypoxanthine, uric acid, and urea, in skeletal muscles, exposed to ischemia and reperfusion, in eight patients having arthroscopic-assisted anterior cruciate ligament reconstruction. A dialysis probe was implanted before surgery in the rectus femoris muscle. Dialysate samples were collected at 10-minute intervals at a flow rate of 1 microL/minute until 2 hours after tourniquet deflation. Ninety minutes of ischemia resulted in accumulation of lactate (234% +/- 38%), hypoxanthine (582% +/- 166%), and glycerol (146% +/- 46%), consumption of glucose (54% +/- 9%) and pyruvate (16% +/- 44%), and a slight decrease of urea (78% +/- 11%) compared with baseline (100%). Uric acid was unchanged (95% +/- 12%). Within 90 minutes after tourniquet deflation the concentrations were virtually normalized for all measured metabolites, suggesting that the duration of ischemia was well tolerated by the patients. The results indicate that the use of microdialysis for monitoring energy metabolic events during orthopaedic surgery that requires ischemia and reperfusion is feasible and safe.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-82225 (URN)15043128 (PubMedID)
    Available from: 2006-09-22 Created: 2006-09-22 Last updated: 2017-12-14Bibliographically approved
    3. Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol
    Open this publication in new window or tab >>Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol
    Show others...
    2009 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 47, no 5, p. 668-673Article in journal, Letter (Refereed) Published
    Abstract [en]

    Oxidative stress has recently been identified as a pivotal pathogenetic factor of bone loss in mice, but its importance in humans is not clear. We aimed to investigate the association between urinary 8-iso-PGF(2 alpha) levels, a major F(2)-isoprostane and a reliable in vivo biomarker of oxidative stress, and bone mineral density (BMD), and to study whether vitamin E in the form of serum alpha-tocopherol, a scavenger of peroxyl radicals, modifies the association. In 405 men, urinary 8-iso-PGF(2 alpha) and serum alpha-tocopherol were measured at age 77 years and BMD at age 82 years. One SD increase in 8-iso-PGF(2 alpha) corresponded to an approximately 2-4% decrease in average adjusted BMD values of total body, lumbar spine, and proximal femur (all P<0.001). Serum alpha-tocopherol levels seemed to modify the association between urinary 8-iso-PGF(2 alpha) and BMD. Men with alpha-tocopherol levels below the median combined with high oxidative stress, i.e., 8-iso-PGF(2 alpha) above the median, had 7% (95% CI 3-11%) lower BMD at the lumbar spine and 5% (95% CI 2-9%) lower BMD at the proximal femur. In elderly men high oxidative stress is associated with reduced BMD, which is more pronounced in individuals with low serum levels of the antioxidant vitamin E.

    Keywords
    BMD, Bone, Isoprostanes, Prostaglandins, Osteoporosis, Vitamin E, α-Tocopherol
    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-109406 (URN)10.1016/j.freeradbiomed.2009.05.031 (DOI)000268995900024 ()19500667 (PubMedID)
    Available from: 2009-10-15 Created: 2009-10-15 Last updated: 2017-12-12Bibliographically approved
    4. Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans
    Open this publication in new window or tab >>Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans
    2012 (English)In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 28, no 4, p. 403-417Article in journal (Refereed) Published
    Abstract [en]

    Objective: The theoretically beneficial effects of coenzyme Q10 (Q10) on exercise-related oxidative stress and physical capacity have not been confirmed to our knowledge by interventional supplementation studies. Our aim was to investigate further whether Q10 supplementation at a dose recommended by manufacturers influences these factors. Methods: Using a randomized, double-blind, controlled design, we investigated the effect on physical capacity of 8 wk of treatment with a daily dose of 90 mg of Q10 (n = 12) compared with placebo (n = 11) in moderately trained healthy men 19 to 44 y old. Two days of individualized performance tests to physical exhaustion were performed before and after the intervention. Primary outcomes were maximal oxygen uptake, workload, and heart rate at the lactate threshold. Secondary outcomes were creatine kinase, hypoxanthine, and uric acid. Results: No significant differences between the groups were discerned after the intervention for maximal oxygen uptake (-0.11 L/min, 95% confidence interval 0.31 to 0.08, P = 0.44), workload at lactate threshold (6.3 W, 13.4 to 25.9, P = 0.36), or heart rate at lactate threshold (2.0 beats/min, -4.9 to 8.9, P = 0.41). No differences between the groups were detected for hypoxanthine or uric acid (serum markers of oxidative stress) or creatine kinase (a marker of skeletal muscle damage). Conclusion: Although in theory Q10 could be beneficial for exercise capacity and in decreasing oxidative stress, the present study could not demonstrate that such effects exist after supplementation with a recommended dose. 

    National Category
    Surgery Medical and Health Sciences
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-110356 (URN)10.1016/j.nut.2011.07.010 (DOI)000302395800011 ()
    Available from: 2009-11-12 Created: 2009-11-12 Last updated: 2018-08-24
  • 1197.
    Östman, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol2009In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 47, no 5, p. 668-673Article in journal (Refereed)
    Abstract [en]

    Oxidative stress has recently been identified as a pivotal pathogenetic factor of bone loss in mice, but its importance in humans is not clear. We aimed to investigate the association between urinary 8-iso-PGF(2 alpha) levels, a major F(2)-isoprostane and a reliable in vivo biomarker of oxidative stress, and bone mineral density (BMD), and to study whether vitamin E in the form of serum alpha-tocopherol, a scavenger of peroxyl radicals, modifies the association. In 405 men, urinary 8-iso-PGF(2 alpha) and serum alpha-tocopherol were measured at age 77 years and BMD at age 82 years. One SD increase in 8-iso-PGF(2 alpha) corresponded to an approximately 2-4% decrease in average adjusted BMD values of total body, lumbar spine, and proximal femur (all P<0.001). Serum alpha-tocopherol levels seemed to modify the association between urinary 8-iso-PGF(2 alpha) and BMD. Men with alpha-tocopherol levels below the median combined with high oxidative stress, i.e., 8-iso-PGF(2 alpha) above the median, had 7% (95% CI 3-11%) lower BMD at the lumbar spine and 5% (95% CI 2-9%) lower BMD at the proximal femur. In elderly men high oxidative stress is associated with reduced BMD, which is more pronounced in individuals with low serum levels of the antioxidant vitamin E.

  • 1198.
    Östman, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sjödin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans2012In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 28, no 4, p. 403-417Article in journal (Refereed)
    Abstract [en]

    Objective: The theoretically beneficial effects of coenzyme Q10 (Q10) on exercise-related oxidative stress and physical capacity have not been confirmed to our knowledge by interventional supplementation studies. Our aim was to investigate further whether Q10 supplementation at a dose recommended by manufacturers influences these factors. Methods: Using a randomized, double-blind, controlled design, we investigated the effect on physical capacity of 8 wk of treatment with a daily dose of 90 mg of Q10 (n = 12) compared with placebo (n = 11) in moderately trained healthy men 19 to 44 y old. Two days of individualized performance tests to physical exhaustion were performed before and after the intervention. Primary outcomes were maximal oxygen uptake, workload, and heart rate at the lactate threshold. Secondary outcomes were creatine kinase, hypoxanthine, and uric acid. Results: No significant differences between the groups were discerned after the intervention for maximal oxygen uptake (-0.11 L/min, 95% confidence interval 0.31 to 0.08, P = 0.44), workload at lactate threshold (6.3 W, 13.4 to 25.9, P = 0.36), or heart rate at lactate threshold (2.0 beats/min, -4.9 to 8.9, P = 0.41). No differences between the groups were detected for hypoxanthine or uric acid (serum markers of oxidative stress) or creatine kinase (a marker of skeletal muscle damage). Conclusion: Although in theory Q10 could be beneficial for exercise capacity and in decreasing oxidative stress, the present study could not demonstrate that such effects exist after supplementation with a recommended dose. 

21222324 1151 - 1198 of 1198
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