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  • 251.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Selection of antibiotic resistance at very low antibiotic concentrations2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, p. 103-107Article, review/survey (Refereed)
    Abstract [en]

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  • 252. Sandler, S
    et al.
    Nilsson, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Andersson, A
    Cryopreservation of mouse pancreatic islets: effects of human serum on islet survival.1987In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 92, no 2, p. 177-184Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the survival of cryopreserved mouse pancreatic islets frozen in the presence of either a simple salt solution (Hanks' balanced salt solution) or a complete tissue culture medium (RPMI 1640). Moreover, the addition of 10% human serum to the freezing solutions was evaluated. Collagenase isolated islets were kept in culture for three days, before being cooled at a rate of 5 degrees C/min or 25 degrees C/min to -70 degrees C, at which temperature the islets were transferred to liquid nitrogen. All freezing media were supplemented with 2 M dimethylsulphoxide as cryoprotectant. The islets were rapidly thawed at 37 degrees C and subsequently cultured for another three days. The recovery of islets was higher when the more rapid cooling rate was used and the addition of serum further improved the recovery. Compared to non-frozen cultured islets there was a loss of cells in all groups of cryopreserved islets, as measured by their DNA content, and this was accompanied by a lowered insulin content. All groups of frozen-thawed islets responded to a high glucose stimulus in vitro with a 5-9 fold increase in insulin secretion. There was no obvious advantage of using a complete tissue culture medium for islet cryopreservation, but the addition of serum had some beneficial effects. Data obtained from non-frozen control islets suggest that human serum slightly impairs the function of mouse pancreatic B-cells.

  • 253. Selassie, Gunilla Rejnö-Habte
    et al.
    Olsson, Ingrid
    Jennische, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Patterns of language and auditory dysfunction in 6-year-old children with epilepsy2009In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, no 2, p. 82-89Article in journal (Refereed)
    Abstract [en]

    In a previous study we reported difficulty with expressive language and visuoperceptual ability in preschool children with epilepsy and otherwise normal development. The present study analysed speech and language dysfunction for each individual in relation to epilepsy variables, ear preference, and intelligence in these children and described their auditory function. Twenty 6-year-old children with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y-6 y 11 mo) and 30 reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range 6 y-6 y 11 mo) were assessed for language and auditory ability. Low scores for the children with epilepsy were analysed with respect to speech-language domains, type of epilepsy, site of epileptiform activity, intelligence, and language laterality. Auditory attention, perception, discrimination, and ear preference were measured with a dichotic listening test, and group comparisons were performed. Children with left-sided partial epilepsy had extensive language dysfunction. Most children with partial epilepsy had phonological dysfunction. Language dysfunction was also found in children with generalized and unclassified epilepsies. The children with epilepsy performed significantly worse than the reference children in auditory attention, perception of vowels and discrimination of consonants for the right ear and had more left ear advantage for vowels, indicating undeveloped language laterality.

  • 254.
    Siegbahn, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Odlind, V.
    Hedner, U.
    Venge, Per
    Coagulation and fibrinolysis during the normal menstrual cycle1989In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 94, no 2, p. 137-152Article in journal (Refereed)
    Abstract [en]

    Thirteen healthy women (age 24-44 yrs) were studied during their menstrual cycle. Samples were taken 2-3 times weekly for six consecutive weeks. Plasma concentrations of oestradiol and progesterone were determined in each blood sample and only women found to be ovulatory were included. From the hormone data the cycles were divided in five phases (early follicular phase, late follicular phase, early luteal phase, late luteal phase and menstrual period). The samples for the coagulation and fibrinolysis assays as well as the venous occlusion (20 min) tests were drawn or performed between 8-9 a m after fasting for 8 hrs. The fibrinogen F VIII:C and AT III were assayed and did not show any variations through the study period. Neither were any differences found in platelet counts, platelet mean volumes or platelet function measured as platelet adhesion and plasma beta-thromboglobulin. The fibrinolytic activity after venous occlusion decreased slightly during the late luteal phase (phase 4) as compared with the other phases. Large individual differences were, however, seen and no statistically significant differences between the five different phases were found. The plasminogen activator inhibitor (PAI-1) varied during the cycle but in most individuals within the normal range. In 7/13 women substantial fluctuations of the fibrinolytic activities during the cycle were seen. Four women had a significant fall of the fibrinolytic activity after venous occlusion during the late luteal phase (phase 4) and 3 others during the menstrual phase (phase 5). No co-variation between the fibrinolytic activities and PAI-1 was found. Multiple regression analysis showed a co-variation between fibrinolytic activities and progesterone.

  • 255.
    Silvemark, Annika Junemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Kallmen, Hakan
    Molander, Carl
    Improved life satisfaction and pain reduction: Follow-up of a 5-week multidisciplinary long-term pain rehabilitation programme2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 278-286Article in journal (Refereed)
    Abstract [en]

    Background. Multidisciplinary rehabilitation programmes can improve physical functioning and help patients with long-term pain back to work. Little is known, however, of the extent to which such rehabilitation also affects life satisfaction, pain severity, and disability. We wanted to evaluate if a 5-week rehabilitation programme for patients with long-term pain improves life satisfaction and decreases pain severity and disability. Methods. The subjects were 164 patients aged 18-65 years from a pain rehabilitation clinic. Most of them were referred from primary care units. One group of repeated tests was used. Participants were asked to fill out the LiSat-11 checklist and parts of the Multidimensional Pain Inventory (MPI), including pain severity, at admission, at discharge, and 1 year after the rehabilitation programme. Results. Satisfaction with life as a whole, and six of ten LiSat-11 domains improved during the follow-up, though none reached the levels for the general population. MPI subscales pain severity, pain interference, life control, and affective distress improved, whereas no change was observed for general activity. Patients older than 38 years decreased more in MPI affective distress than younger patients. Gender, pain severity, and work status before the programme did not significantly influence the outcome. Conclusions. The results indicate that multidisciplinary rehabilitation improves life satisfaction, reduces pain severity, and reduces negative psychological, social, and behavioural effects of pain. These outcome variables relate to domains known to be of interest for patients and should therefore be considered for evaluation of rehabilitation programmes for long-term pain.

  • 256.
    Singh, Umashankar
    et al.
    Indian Inst Technol, Biol Sci & Engn, Gandhinagar, Gujarat, India..
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    CGGBP1-an indispensable protein with ubiquitous cytoprotective functions2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 219-232Article, review/survey (Refereed)
    Abstract [en]

    The human genome contains multiple stretches of CGG trinucleotide repeats, which act as transcription- and translation-regulatory elements but at the same time form secondary structures that impede replication and give rise to sites of chromosome fragility. Proteins binding to such DNA elements may be involved in divergent cellular processes such as transcription, DNA damage, and epigenetic state of the chromatin. We review here the work done on CGG repeats and associated proteins with special focus on a factor called CGGBP1. CGGBP1 presents with an interesting example of factors that do not have any single dedicated function, but participate indispensably in multiple processes. Both experimental results and data from cancer genome sequencing have revealed that any alteration in CGGBP1 that compromises its function is not tolerated by normal or cancer cells alike. Based upon a large amount of published data, information from databases, and unpublished results, we decipher in this review how CGGBP1 is a classic example of the one factor, divergent functions' paradigm of cytoprotection. By taking cues from the studies on CGGBP1, more such factors can be discovered for a better understanding of the evolution of mechanisms of cellular survival.

  • 257.
    Skogsdal, Yvonne
    et al.
    Orebro Univ, Fac Med & Hlth, Maternal Hlth Care Unit, Orebro, Sweden.
    Fadl, Helena
    Orebro Univ, Fac Med & Hlth, Dept Obstet & Gynecol, Orebro, Sweden.
    Cao, Yang
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Biostat, Orebro, Sweden.
    Karlsson, Jan
    Orebro Univ, Fac Med & Hlth, Univ Hlth Care Res Ctr, Orebro, Sweden.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    An intervention in contraceptive counseling increased the knowledge about fertility and awareness of preconception health-a randomized controlled trial2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 203-212Article in journal (Refereed)
    Abstract [en]

    Background: Reproductive life plan counseling (RLPC) is a tool to encourage women and men to reflect upon their reproduction, to avoid unintended pregnancies and negative health behavior that can threaten reproduction. The aim was to evaluate the effect of RLPC among women attending contraceptive counseling. Outcomes were knowledge about fertility and awareness of preconception health, use of contraception, and women's experience of RLPC. Material and methods: Swedish-speaking women, aged 20-40 years, were randomized to intervention group (IG) or control group (CG). Participants (n = 1,946) answered a questionnaire before and two months after (n = 1,198, 62%) the consultation. All women received standard contraceptive counseling, and the IG also received the RLPC, i.e. questions on reproductive intentions, information about fertility, and preconception health. Results: Women in the IG increased their knowledge about fertility: age and fertility, chances of getting pregnant, fecundity of an ovum, and chances of having a child with help of IVF. They also increased their awareness of factors affecting preconception health, such as to stop using tobacco, to refrain from alcohol, to be of normal weight, and to start with folic acid before a pregnancy. The most commonly used contraceptive method was combined oral contraceptives, followed by long-acting reversible contraception. Three out of four women (76%) in the IG stated that the RLPC should be part of the routine in contraceptive counseling. Conclusions: Knowledge about fertility and awareness of preconception health increased after the intervention. The RLPC can be recommended as a tool in contraceptive counseling.

  • 258. Skram, Marius Kurås
    et al.
    Gulati, Sasha
    Larsson, Erik
    Lindal, Sigurd
    Torp, Sverre Helge
    Muscle biopsies in children: an evaluation of histopathology and clinical value during a 5-year period2009In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, no 1, p. 41-45Article in journal (Refereed)
    Abstract [en]

    Muscle biopsy is an important diagnostic tool in the investigation of children with neuromuscular disorders. This report presents the experience with paediatric muscle biopsies during a 5-year period at a routine pathology laboratory. A total number of 58 cases were included, and indications, microscopical findings, and final histopathological diagnoses were recorded. A total of 21 biopsies were from females (36%) and 37 biopsies from males (64%); 53% of the cases were from children under 2 years of age. Major pathological findings were found in 30% comprising muscular dystrophy, neurogenic atrophy, and congenital and metabolic disorders, even in cases with vague clinical manifestations. These findings confirm the high diagnostic yield of muscle biopsies, especially as new techniques have been introduced such as immunohistochemistry. Muscle pathology is difficult and emphasizes the importance of this service being undertaken by specialized laboratories with an experienced staff. Microscopical examination of muscle biopsies should be based on adequate clinical information, demonstrating the necessity of close contact between pathologists and referring physicians.

  • 259.
    Snäckerström, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansen, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    De-identified linkage of data across separate registers: a proposal for improved protection of personal information in registry-based clinical research2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 29-32Article in journal (Refereed)
    Abstract [en]

    Over the last decades the advent of digital documentation has provided research communities with valuable resources of information for clinical research. To utilize the potential of information about patients, their health care, and its outcome that is already available in different registers, the possibility to cross-reference information from different registers is inevitably required. When performing linkage, we are currently forced to disclose information of participating subjects either to the administration of the other register(s) or to the researcher. Considering the increased concern of issues around personal integrity, this is a limitation that affects the ethical implications of proposed research and that might in the end affect the willingness of subjects to participate in registers. For this reason we propose a different methodology for performing cross-referencing, one that effectively prevents information leakage between the different organizations participating in linking the data. We believe that it is possible to use commonly adopted technologies within the area of data security and encryption to perform linkage without disclosing any sensitive information between different participants. In this paper we demonstrate how common techniques of encryption could be implemented to achieve that and furthermore significantly simplify discovery and feasibility surveying ahead of studies.

  • 260.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kals, Jaak
    Low dialysate potassium and central arterial pressure waveform2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 3, p. 207-212Article in journal (Refereed)
    Abstract [en]

    Background. Cardiovascular mortality is high in hemodialysis (HD) patients. Early arterial pressure wave reflections predict mortality in HD patients, and HD acutely improves the central pressure waveform. Potassium (K) plays a crucial role in cardiac electrophysiology, and patients with end-stage kidney disease depend on HD for neutral K balance. We aimed to study the impact of dialysate K concentrations on central arterial pressure waveform. Methods. Thirty-three chronic HD patients were studied before and after a HD session, and the prescribed dialysate K concentration was recorded. In a subset of 23 patients without arrhythmias, pulse wave analysis was performed on radial arteries. Nine patients had dialysate K set to 1 mmol/L (group 1), and 14 patients had K set to 2 or 3 mmol/L (group 2). Augmentation index (AIx), defined as difference between the second and first systolic peak divided by central pulse pressure, was used as a measure of arterial stiffness. Results. HD reduced the AIx in group 1 only (p = 0.0005). Likewise, central systolic pressure was reduced in group 1 only (p = 0.006). The relative reduction of AIx post-HD was significantly higher in group 1 compared with group 2 (p < 0.0001). The association between low dialysate K and AIx reduction remained statistically significant after adjustment for variables including the change in central and peripheral systolic pressure and mean arterial pressure. Conclusion. Low dialysate K is strongly and independently associated with the acute improvement of AIx.

  • 261.
    Stridh, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Linköping university.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Inhibition of hyaluronan synthesis in rats reduces renal ability to excrete fluid and electrolytes during acute hydration2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 217-221Article in journal (Refereed)
    Abstract [en]

    Background. Hyaluronan (HA) is the dominant glycosaminoglycan in the renomedullary interstitium. Renomedullary HA has been implicated in tubular fluid handling due to its water-attracting properties and the changes occurring in parallel to acute variations in the body hydration status.

    Methods. HA production was inhibited by 4-methylumbelliferone (4-MU in drinking water for 5 days, 1.45 ± 0.07 g/day/kg body weight) in rats prior to hydration.

    Results. Following hypotonic hydration for 135 min in control animals, diuresis and osmotic excretion increased while sodium excretion and glomerular filtration rate (GFR) remained unchanged. The medullary and cortical HA contents were 7.85 ± 1.29 ng/mg protein and 0.08 ± 0.01 ng/mg protein, respectively. Medullary HA content after 4-MU was 38% of that in controls (2.98 ± 0.95 ng/g protein, p < 0.05), while the low cortical levels were unaffected. Baseline urine flow was not different from that in controls. The diuretic response to hydration was, however, only 51% of that in controls (157 ± 36 versus 306 ± 54 µl/g kidney weight/135 min, p < 0.05) and the osmolar excretion only 47% of that in controls (174 ± 47 versus 374 ± 41 µOsm/g kidney weight/135 min, p < 0.05). Sodium excretion, GFR, and arterial blood pressure were similar to that in control rats and unaltered during hydration.

    Conclusions. Reduction of renomedullary interstitial HA using 4-MU reduces the ability of the kidney to respond appropriately upon acute hydration. The results strengthen the concept of renomedullary HA as a modulator of tubular fluid handling by changing the physicochemical properties of the interstitial space.

  • 262.
    Stridh, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Takahashi, Tomoko
    Hoshi University, Tokyo, Japan .
    Ikegami-Kawai, Mayumi
    Hoshi University, Tokyo, Japan .
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Inhibition of mTOR activity in diabetes mellitus reduces proteinuria but not renal accumulation of hyaluronan2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 233-240Article in journal (Refereed)
    Abstract [en]

    Objectives. Accumulation of extracellular matrix (ECM) components is an early sign of diabetic nephropathy. Also the glycosaminoglycan hyaluronan (HA) is elevated in the renal interstitium during experimental diabetes. The mammalian target of rapamycin (mTOR) pathway participates in the signaling of hyperglycemia-induced ECM accumulation in the kidney, but this has not yet been investigated for HA. We hypothesized that interstitial HA accumulation during diabetes may involve mTOR activation.Methods. Diabetic rats (6 weeks post-streptozotocin (STZ)) were treated with rapamycin to inhibit mTOR or vehicle for 2 additional weeks. Kidney function (glomerular filtration rate, renal blood flow, urine output) and regional renal HA content were thereafter analyzed. The ability of the animals to respond to desmopressin was also tested.Results. Diabetic animals displayed hyperglycemia, proteinuria, hyperfiltration, renal hypertrophy, increased diuresis with reduced urine osmolality, and reduced weight gain. Cortical and outer medullary HA was elevated in diabetic rats. Urine hyaluronidase activity was almost doubled in diabetic rats compared with controls. The ability to respond to desmopressin was absent in diabetic rats. Renal blood flow and arterial blood pressure were unaffected by the diabetic state. In diabetic rats treated with rapamycin the proteinuria was reduced by 32%, while all other parameters were unaffected.Conclusion. Regional renal accumulation of the ECM component HA is not sensitive to mTOR inhibition by rapamycin, while proteinuria is reduced in established STZ-induced diabetes. Whether the diabetes-induced renal accumulation of HA occurs through different pathways than other ECM components, or is irreversible after being established, remains to be shown.

  • 263.
    Stålhammar, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Håkansson, Lena Douhan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Differential Neutrophil Chemotactic Response towards IL-8 and Bacterial N-formyl Peptides in Term Newborn Infants2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A prerequisite for an effective innate immunity is the migrative ability of neutrophils to respond to inflammatory and infectious agents such as the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic capacity of neutrophils from newborn infants and adults in response to IL-8 and the bacterial peptide fMLP.

    METHODS: In the under-agarose cell migration assay, isolated leukocytes from healthy adults and from cord blood of healthy term newborn infants were studied with dose responses towards IL-8 and fMLP. The same number of leukocytes (1 × 10(5) cells), with the same distribution of neutrophils and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil pattern of migration, i.e. the migration distance and the number of migrating neutrophils per distance, was evaluated.

    RESULTS: In comparison to adults, fewer neutrophils from newborn infants migrated towards IL-8 and for a shorter distance (P < .01, respectively). The number of neutrophils migrating to different gradients of fMLP, the distance they migrated, and the correlation between the number and the distance were the same for neonates and adults. Random migration did not differ in any instance.

    CONCLUSION: Chemotaxis of neutrophils from newborn infants was as co-ordinated as neutrophils from adults in response to fMLP, whereas the response to IL-8 was reduced. The differential response of neutrophils from neonates to intermediate and end-target chemoattractants could indicate a reduced infectious response.

  • 264. Sunde, Kathrin
    et al.
    Nilsen, Tom
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Performance characteristics of a cystatin C immunoassay with avian antibodies2007In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 112, no 1, p. 21-37Article in journal (Refereed)
    Abstract [en]

    Background: A new particle-enhanced turbidimetric immunoassay (PETIA) with avian antibodies for measuring serum/plasma cystatin C has been developed. The performance characteristics of the assay are described. Methods: Measurements were performed on a Roche Modular P and on an Abbott Architect ci8200 using Gentian cystatin C immunoassay. Results: Measuring range was 0.3 - 8.0 mg/ L. Reference range was 0.57 - 1.09 mg/ L. Total analysis time was 10 minutes. Linearity was absolute over the whole assay range. Recovery of samples and controls was within 98.6 - 109.4%. Total imprecision CV, measured over 20days with two lots, was <= 4.2%. Comparision with a particle enhanced nephelometric cystatin C immunoassay (PENIA) by linear regression resulted in a slope within 0.97 - 1.02 and intercept within +/- 0.05 mg/ L. Interference studies with drugs, anticoagulants, intralipid (<= 11g/L), triglycerides (<= 14 g/L) and bilirubin (<= 420 mg/L) showed no significant interference. Due to the use of avain antibodies, no interference with rheumatoid factor was observed. No carry-over was detected. Lower detection limit and lower quantification limit (CV <= 6%) were both below 0.33 mg/L, which is less than the lowest standard. Sample stability was up to one month at 2 - 8 degrees C. Stability of the reagents at 2 - 8 degrees C was estimated to be 24 months. Stability of the reagents in use was minimum 9 weeks. Conclusions: Gentian cystatin C PETIA is shown to have excellent performance between methods. Interference results are improved due to avian antibodies and a broader span of the calibration curve. Avian antibodies are also known to have better immune response than mammalian antibodies towards mammalian antigens.

  • 265.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Björkelund, Cecilia
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med Primary Hlth Care, Gothenburg, Sweden.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hansson, Per-Olof
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Koupil, Ilona
    Stockholm Univ, Dept Publ Hlth Sci, Stockholm, Sweden;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Kristenson, Margareta
    Linkoping Univ, Dept Med & Hlth Sci, Div Community Med, Linkoping, Sweden.
    Lagerros, Ylva Trolle
    Karolinska Inst, Dept Med, Unit Clin Epidemiol, Stockholm, Sweden;Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Huddinge, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lissner, Lauren
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med Epidemiol & Social, Gothenburg, Sweden.
    Johansson, Ingegerd
    Umea Univ, Sch Dent, Dept Odontol, Umea, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Orebro Univ, Orebro Univ Hosp, Dept Pediat, Orebro, Sweden.
    Nilsson, Peter M.
    Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden;Lund Univ, Lund, Sweden.
    Olsson, Håkan
    Lund Univ, Dept Clin Sci Canc Epidemiol, Lund, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Karlsson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rosengren, Annika
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Sandin, Sven
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA;Seaver Autism Ctr Res & Treatment Mt Sinai, New York, NY USA.
    Snäckerström, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stenbeck, Magnus
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Umea Univ, Heart Ctr, Umea, Sweden.
    Weiderpass, Elisabete
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Inst Populat Based Canc Res, Dept Res, Canc Registry Norway, Oslo, Norway;Univ Helsinki, Fac Med, Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland;Univ Tromso, Arctic Univ Norway, Dept Community Med, Tromso, Norway.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wennberg, Patrik
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Fortier, Isabel
    McGill Univ, Res Inst, Hlth Ctr, Montreal, PQ, Canada.
    Heller, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storgärds, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rationale for a Swedish cohort consortium2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

  • 266.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Nowrouzi, Shamim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Marttala, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekman, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Öhagen, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The Precision HYpertenSIon Care (PHYSIC) study: a double-blind, randomized, repeated cross-over study2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 51-58Article in journal (Refereed)
    Abstract [en]

    High blood pressure is the leading risk factor for premature deaths and a major cost to societies worldwide. Effective blood pressure-lowering drugs are available, but patient adherence to them is low, likely partly due to side effects. To identify patient-specific differences in treatment effects, a repeated cross-over design, where the same treatment contrasts are repeated within each patient, is needed. Such designs have been surprisingly rarely used, given the current focus on precision medicine. The Precision HYpertenSIon Care (PHYSIC) study aims to investigate if there is a consistent between-person variation in blood pressure response to the common blood pressure-lowering drug classes of a clinically relevant magnitude, given the within-person variation in blood pressure. The study will also investigate the between-person variation in side effects of the drugs. In a double-blind, randomized, repeated cross-over trial, 300 patients with mild hypertension will be treated with four blood pressure-lowering drugs (candesartan, lisinopril, amlodipine, and hydrochlorothiazide) in monotherapy, with two of the drugs repeated for each patient. If the study indicates that there is a potential for precision hypertension care, the most promising predictors of blood pressure and side effect response to the drugs will be explored, as will the potential for development of a biomarker panel to rank the suitability of blood pressure-lowering drug classes for individual patients in terms of anticipated blood pressure effects and side effects, with the ultimate goal to maximize adherence. The study follows a protocol pre-registered at ClinicalTrials.gov with the identifier NCT02774460.

  • 267.
    Svensson, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lundström, Kristina Lamberg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Cherif, Honar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Utility of bronchoalveolar lavage in diagnosing respiratory tract infections in patients with hematological malignancies: are invasive diagnostics still needed?2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 56-60Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients treated for hematological malignancies have an increased risk of serious infections. Diagnosis and prompt initiation of therapy are essential. Bronchoalveolar lavage (BAL) is a well-established investigation for identifying the cause of pulmonary infiltrates in immunocompromised patients. The aim of the study was to determine the diagnostic yield of BAL in patients treated for hematological malignancies and how often it contributed to a modification of the anti-infectious therapy.

    METHODS: We reviewed records from 151 consecutive BAL procedures in 133 adult patients with hematological malignancies, treated at a tertiary hematology unit from 2004 to 2013. Extensive microbiological work-ups on BAL samples had been performed according to a standardized protocol.

    RESULTS: A microbiological finding causing the infectious episode could be identified in 59 (39%) cases. In 44 (29%) of the cases, results from BAL had an impact on clinical management either by contributing to a specific diagnosis (25%) or by leading to cessation of ongoing microbiological therapy. The most common diagnoses were invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). Diagnoses of IPA and PJP were based on results from BAL in 65% and 93% of cases, respectively. Several microbiological tests on BAL samples rendered no positive results. Complications were few and mainly mild.

    CONCLUSION: BAL is still important for either verifying or excluding some of the most important respiratory tract pathogens in patients with hematological malignancies, particularly IPA and PJP. Standardized procedures for BAL sampling should be continually revised to exclude unnecessary microbiological tests.

  • 268.
    Swartling, Fredrik J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Myc proteins in brain tumor development and maintenance2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 2, p. 122-131Article, review/survey (Refereed)
    Abstract [en]

    Myc proteins are often deregulated in human brain tumors, especially in embryonal tumors that affect children. Many observations have shown how alterations of these pleiotropic Myc transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the role of Myc family members (particularly c-myc and Mycn) in tumors like medulloblastoma and glioma and will further discuss how to target stabilization of these proteins for future brain tumor therapies.

  • 269.
    Swartling, Fredrik Johansson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Identifying Candidate Genes Involved in Brain Tumor Formation2008In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 113, no 1, p. 1-38Article, review/survey (Refereed)
    Abstract [en]

    Malignant primary brain tumors, gliomas, often overexpress both platelet-derived growth factor (PDGF) ligands and receptors providing an autocrine and/or paracrine boost to tumor growth. Glioblastoma multiforme (GBM) is the most frequent glioma. Its aggressive and infiltrative growth renders it extremely difficult to treat. Median survival after diagnosis is currently only 12-14 months. The present review describes the use of retroviral tagging to identify candidate cancer-causing genes that cooperate with PDGF in brain tumor formation. Newborn mice injected intracerebrally with a Moloney murine leukemia retrovirus carrying the sis/PDGF-B oncogene and a replication competent helper virus developed brain tumors with many characteristics of human gliomas. Analysis of proviral integrations in the brain tumors identified almost 70 common insertion sites (CISs). These CISs were named brain tumor loci and harbored known but also putative novel cancer-causing genes. Microarray analysis identified differentially expressed genes in the mouse brain tumors compared to normal brain. Known tumor genes and markers of immature cells were upregulated in the tumors. Tumors developed 13-42 weeks after injection and short latency tumors were further distinguished as fast growing and GBM-like. Long latency tumors resembled slow-growing oligodendrogliomas and contained significantly less integrations as compared to short latency tumors. Several candidate genes tagged in this retroviral screen have known functions in neoplastic transformation and oncogenesis. Some candidates with a previously unknown function in tumorigenesis were found and their putative role in brain tumor formation will be discussed in this review. The results show that proviral tagging may be a useful tool in the search for candidate glioma genes.

  • 270.
    Tammivaara-Hilty, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Central Haemodynamics at Rest and during Exercisein Severe Chronic Obstructive Lung Disease1972In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 77, no 3, p. 149-162Article in journal (Refereed)
    Abstract [en]

    Twenty-five patients of ages 39-72 years, with a maximumventilatory capacity (MVVF) of < 35 % of the predicted values,were classified into a respiratory insufficiency (R) and a comparison(C) group according to the clinical progress of thedisease. With the patients in their habitual state, the totalhaemoglobin (THb, g), the pulmonary and systemic pressures,cardiac output (Q, l/min) and pulmonary (PVR) and systemic(SVR) vascular resistance in (mmHg/l). min were measuredat rest and during work.The mean values and S.E.M. in groups R and C were asfollows: for THb 7.4f0.3 and 8.6f0.5 g/kg, blood volume59.1 f 2.0 and 64.9 f2 .8 ml/kg, S ~ O8,6 .2+ 2.2 and 90.4 f 1.4 Yo,avos 48.5f2.5 and 53.2f2.6 ml/l, pulmonary arterial meanpressure 31+ 2 and 26f 2 mmHg, PVR 4.7f 0.5 and 3.2k 0.3(mmHg/l). min, arterial mean pressure 105f4 and 102f4mmHg, SVR 23.1f1.2 and 23.9k1.8 (mmHg/l). min. Qwas 4.5 f 0.2 in the R-group male patients and 4.7f 0.3 I/minin the females, and 4.5f 0.3 in the C-group male patients and3.5 I/min in the one female patient.During work (not performed in all patients of group R) atmean work loads of 160 kpm/min in 4 male patients of groupR, Q was 6.5f 0.5 l/min, at 90 kpm/min in 3 female patients ofgroup R 6.4f0.2 I/min, at 150 kpm/min in 10 male patientsof group C 6.7k 0.4 I/& and at 150 kpmimin in the femalepatient of group C 5.2 I/min. It is emphasized that both theright and

  • 271.
    Tammivaara-Hilty, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Physical Working Capacity in Severe ChronicObstructive Lung Disease1972In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 77, no 3, p. 189-201Article in journal (Refereed)
    Abstract [en]

    Twenty-five patients (mean age 61+2, range 39-72 years)with severe chronic obstructive lung disease, with a maximumvoluntary ventilation (MWF), without bronchodilating spray,< 35 % of the individually predicted normal value, were classifiedinto two groups: (1) a group who had suffered from atleast one period of absolute respiratory insufficiency (R), with8 men and 6 women, and (2) a comparison (C) group withthe corresponding degree of MVVF limitation but withoutany period of absolute respiratory insufficiency, with 10 menand 1 woman. The patients were studied in their habitualstate by a standard ergometer-bicycle exercise test. Thehighest performed work load, near maximal (Wmax), wasdetermined, and also the pulmonary gas exchange, arterialblood(0, and CO,) gas tensions, lactate concentration andacid-base balance under the conditions of maximum work load.MVVF and W,,, were found to be positively correlatedin the R and C groups, but not in the female patients. W,,,was also correlated to other factors, namely negatively toresting FRC/TLC and RV/TLC, and to V,/ V, measured undermaximum working conditions. Average W,,, was 189+ 52 inthe male R group and 118+37 kpm/min in the female, andin the male C group 256+40 kpm/min. W,,, in kpm/minper kg body weight was in the R group 2.63+ 0.57 and in theC group 4.29k0.65. There was a tendency to lower PaOIand CaO, during maximum work and higher heart rate in relationto work load in the R group than in the C group althoughthis was not statistically significant.

  • 272.
    Tegler, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 229-235Article in journal (Refereed)
    Abstract [en]

    Objective. The aetiology and early pathophysiological mechanisms of aortic aneurysm formation are still unknown and challenging to study in vivo. Positron emission tomography (PET) is a potentially valuable instrument for non-invasive in vivo pathophysiological studies. No specific tracer to identify the pathophysiological process of aneurysmal dilatation is yet available, however. The aim of this study was to explore if different PET tracers could be useful to image aneurysmal disease. Methods and results. Human aneurysmal aortic tissue, collected during elective resection of abdominal aortic aneurysm (AAA) of asymptomatic patients, was investigated in vitro by means of autoradiography with [Ga-68]CRP-binder targeting C-reactive protein, [C-11]DAA1106 targeting translocator protein (18 kDa), [C-11]D-deprenyl with unknown target receptor, [C-11] deuterium-L-deprenyl targeting astrocytes, [F-18]fluciclatide targeting integrin alpha(V)beta(3), [Ga-68]IMP461 and bi-specific antibody TF2 052107 targeting carcinoembryonic antigen, [F-18]F-metomidate targeting mitochondrial cytochrome P-450 species in the adrenal cortex, and [F-18]vorozole targeting aromatase. Of the investigated tracers, only [F-18]fluciclatide exhibited specific binding, whereas the other PET tracers failed to show specific uptake in the investigated tissue and are probably not useful for the intended purpose. Conclusion. It seems likely that alpha(V)beta(3) integrin expression in AAA can be visualized with PET and that the alpha(V)beta(3) selective tracer, [F-18]fluciclatide, may be suitable for in vivo molecular imaging of asymptomatic AAA. Additional evaluation of [F-18]fluciclatide and alpha(V)beta(3) integrin expression in AAA will be performed in vitro as well as in vivo.

  • 273.
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Cyclic AMP dynamics in the pancreatic beta-cell2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 4, p. 355-369Article, review/survey (Refereed)
    Abstract [en]

    Insulin secretion from pancreatic beta-cells is tightly regulated by glucose and other nutrients, hormones, and neural factors. The exocytosis of insulin granules is triggered by an elevation of the cytoplasmic Ca2+ concentration ([Ca2+](i)) and is further amplified by cyclic AMP (cAMP). Cyclic AMP is formed primarily in response to glucoincretin hormones and other G(s)-coupled receptor agonists, but generation of the nucleotide is critical also for an optimal insulin secretory response to glucose. Nutrient and receptor stimuli trigger oscillations of the cAMP concentration in beta-cells. The oscillations arise from variations in adenylyl cyclase-mediated cAMP production and phosphodiesterase-mediated degradation, processes controlled by factors like cell metabolism and [Ca2+](i). Protein kinase A and the guanine nucleotide exchange factor Epac2 mediate the actions of cAMP in beta-cells and operate at multiple levels to promote exocytosis and pulsatile insulin secretion. The cAMP signaling system contains important targets for pharmacological improvement of insulin secretion in type 2 diabetes.

  • 274.
    Thorbjörnsen, Knut
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Svensjö, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Falun Cty Hosp, Dept Surg, Falun, Sweden.
    Gidlund, Khatereh Djavani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Gilgen, Nils-Peter
    Eskilstuna Cty Hosp, Dept Surg, Eskilstuna, Sweden.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Prevalence and natural history of and risk factors for subaneurysmal aorta among 65-year-old men2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 180-186Article in journal (Refereed)
    Abstract [en]

    Background: The aims of this study were to determine the prevalence of screening-detected subaneurysmal aorta (SAA), i.e. an aortic diameter of 2.5-2.9 cm, its associated risk factors, and natural history among 65-year-old men.

    Methods: A total of 14,620 men had their abdominal aortas screened with ultrasound and completed a health questionnaire containing information on smoking habits and medical history. They were categorized based on the aortic diameter: normal aorta (n = 14,129), SAA (2.5-2.9 cm; n = 258), and abdominal aortic aneurysm (AAA) (>= 3.0 cm; n = 233). The SAA-group was rescanned after 5 years. Associated risk factors were analyzed.

    Results: The SAA-prevalence was 1.9% (95% confidence interval 1.7%-2.1%), with 57.0% (50.7%-63.3%) expanding to >= 3.0 cm within 5 years. Frequency of smoking, coronary artery disease, hypertension, hyperlipidemia, and claudication were significantly higher in those with SAA and AAA compared to those with normal aortic diameter. Current smoking was the strongest risk factor for SAA (odds ratio [OR] 2.8; P < 0.001) and even stronger for AAA (OR 3.6; P < 0.001). Men with SAA expanding to AAA within 5 years presented pronounced similarities to AAA at baseline.

    Conclusions: Men with SAA and AAA presented marked similarities in the risk factor profile. Smoking was the strongest risk factor with an incremental association with disease severity, and disease progression. This indicates that SAA and AAA may have the same pathophysiological origin and that SAA should be considered as an early stage of aneurysm formation. Further research on the cost-effectiveness and potential benefits of surveillance as well as smoking cessation and secondary cardiovascular prevention in this subgroup is warranted.

  • 275.
    Thornadtsson, Alexandra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Drca, Nikola
    Karolinska Inst, Dept Med; Karolinska Univ Hosp, Dept Cardiol.
    Ricciardolo, Fabio
    Univ Torino, Div Resp Dis, Dept Clin & Biol Sci, Turin, Italy..
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Increased levels of alveolar and airway exhaled nitric oxide in runners2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 2, p. 85-91Article in journal (Refereed)
    Abstract [en]

    Aim: The objective of this study was to apply extended NO analysis for measurements of NO dynamics in the lung, divided into alveolar and airway contribution, in amateur runners and marathoners. Methods: The athletes participated in either a marathon or a half marathon. The athletes self-reported their age, weight, height, training distance per week, competing distance, cardio-pulmonary health, atopic status, and use of tobacco. Measurements of exhaled NO (FENO) with estimation of alveolar NO (CANO) and airway flux (J(aw)NO), ventilation, pulse oximetry, and peak flow were performed before, immediately after, and 1hour after completing the race. Results: At baseline the alveolar NO was higher in amateur runners, 2.91.1ppb (p=0.041), and marathoners, 3.6 +/- 1.9ppb (p=0.002), than in control subjects, 1.4 +/- 0.5ppb. J(aw)NO was higher in marathoners, 0.90 +/- 0.02 nLs(-1) (p=0.044), compared with controls, 0.36 +/- 0.02 nLs(-1), whereas the increase in amateur runners, 0.56 +/- 0.02 nLs(-1), did not attain statistical significance (p=0.165). Immediately after the race there was a decrease in FENO in both amateur runners and marathoners, whereas CANO and J(aw)NO were decreased in marathoners only. Conclusion: Our results support the view that there is an adaptation of the lung to exercise. Thus strenuous exercise increased both airway and alveolar NO, and this might in turn facilitate oxygen uptake.

  • 276.
    Thörn, Mari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Finnström, Niklas
    Lundgren, Stefan
    Rane, Anders
    Lööf, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Expression of cytochrome P450 and MDR1 in patients with proctitis2007In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 112, no 3, p. 303-312Article in journal (Refereed)
    Abstract [en]

    Background. The aim of this study was to investigate the effect of inflammation on the gene expression of three cytochrome P450's (CYP) and P-glycoprotein (P-gp) in the rectal and colonic mucosa in patients with proctitis. Methods. Biopsies were obtained from inflamed and normal mucosa in association with routine sigmoidoscopy in patients with proctitis. The biopsies were snap-frozen in liquid nitrogen. Real time PCR (polymerase chain reaction) was used for quantitative analyses of mRNA specific for the CYP2E1, CYP3A4 and CYP3A5 gene and the MDR1 genes. Values were normalised based on gene expression of beta-actin to enable comparisons between samples. Results. The gene expression of CYP2E1 and CYP3A4 was lower in mucosa with severe inflammation vs normal mucosa (p<0.05). For CYP3A5 and P-gp there was no significant difference when comparing normal and inflammatory changed mucosa. Conclusion. Our study suggests that at least for some of the CYP enzymes the expression decreases in response to the inflammatory process in the gastrointestinal tract.

  • 277.
    Tonkonogi, Aleksandra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Helmersson-Karlqvist, Johanna
    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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 174-178Article in journal (Refereed)
    Abstract [en]

    AIM: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes.

    METHODS: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7-13.4 years), 33 participants died of cardiovascular causes.

    RESULTS: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03-2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk.

    CONCLUSION: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.

  • 278.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Why is preconception health and care important?2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 4, p. 207-207Article in journal (Other academic)
  • 279.
    Tydén, Tanja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Verbiest, Sarah
    Univ N Carolina, Sch Social Work, Chapel Hill, NC 27514 USA.;Univ N Carolina, Ctr Maternal & Infant Hlth, Chapel Hill, NC 27514 USA.;Natl Preconcept Hlth & Hlth Care Initiat, Chapel Hill, NC USA..
    van Achterberg, Theo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Katholieke Univ Leuven, Dept Publ Hlth & Primary Care, Acad Ctr Nursing & Midwifery, Leuven, Belgium..
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stern, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Using the Reproductive Life Plan in contraceptive counselling2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 4, p. 299-303Article in journal (Refereed)
    Abstract [en]

    Having children or not is one of the most important decisions that a person will make in his or her lifetime. The Reproductive Life Plan (RLP) is a protocol that aims to encourage both women and men to reflect on their reproductive intentions and to find strategies for successful family planning, for example to have the wanted number of children and to avoid unwanted pregnancies as well as ill-health that may threaten reproduction. The RLP was developed in an American context for promotion of reproductive health in a life cycle perspective. Few studies have systematically evaluated the effectiveness of using an RLP protocol in clinical practice. This article describes the application of using the RLP protocol in contraceptive counselling in Sweden.

  • 280.
    Tängdén, Thomas Grenholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, p. 149-153Article, review/survey (Refereed)
    Abstract [en]

    Combination antibiotic therapy for Gram-negative sepsis is controversial. The present review provides a brief summary of the existing knowledge on combination therapy for severe infections with multidrug-resistant Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae. Empirical combination antibiotic therapy is recommended for severe sepsis and septic shock to reduce mortality related to inappropriate antibiotic treatment. Because definitive combination therapy has not been proven superior to monotherapy in meta-analyses, it is generally advised to de-escalate antibiotic therapy when the antibiotic susceptibility profile is known, although it cannot be excluded that some subgroups of patients might still benefit from continued combination therapy. Definitive combination therapy is recommended for carbapenemase-producing Enterobacteriaceae and should also be considered for severe infections with Pseudomonas and Acinetobacter spp. when beta-lactams cannot be used. Because resistance to broad-spectrum beta-lactams is increasing in Gram-negative bacteria and because no new antibiotics are expected to become available in the near future, the antibacterial potential of combination therapy should be further explored. In vitro data suggest that combinations can be effective even if the bacteria are resistant to the individual antibiotics, although existing evidence is insufficient to support the choice of combinations and explain the synergistic effects observed. In vitro models can be used to screen for effective combinations that can later be validated in animal or clinical studies. Further, in the absence of clinical evidence, in vitro data might be useful in supporting therapeutic decisions for severe infections with multidrug-resistant Gram-negative bacteria.

  • 281.
    Uddenfeldt, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Rask-Andersen, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Sensitization to pets is a major determinant of persistent asthma and new asthma onset in Sweden2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 2, p. 111-121Article in journal (Refereed)
    Abstract [en]

    Introduction. Our knowledge about atopy as a longitudinal predictor of asthma is limited. The purpose of this study was to investigate the prognosis of asthma and risk factors for asthma onset, especially sensitization of specific allergens in a population sample.

    Material and methods. A cohort responded to a respiratory questionnaire in 1990 and 2003. At baseline, 2,060 subjects who, in the screening questionnaire, reported respiratory symptoms and 482 controls were investigated with interviews, spirometry, and skin-prick test. A total of 721 asthmatics and 976 subjects without respiratory disease were clinically verified. At follow-up in 2003, 340 subjects with persistent asthma and 186 subjects with asthma remission were identified, while 76 subjects reported new asthma onset.

    Results. Sensitization to pets and a high symptom score were significant determinants of persistent asthma (odds ratio (OR) 3.2 (95% CI 1.9-5.6) and 5.7 (2.5-13.3), respectively) and onset of asthma (OR 2.6 (1.1-6.0), and 1.7 (1.2-2.3)). A high self-reported responsiveness to airway irritants (OR 1.6 (1.1-2.2)), and more asthma medications (OR 2.0 (1.3-2.9)) were additional indicators of persistent asthma at the follow-up. Belonging to the older age group decreased the risk both of having persistent asthma and asthma onset.

    Discussion. Asthmatics sensitized to pets have a more severe outcome than asthmatics not sensitized to pets. Sensitization to pets was also a strong predictor for onset of asthma. Special attention should be given to asthmatics who report having severe symptoms and problems with airway irritants as such patients are more likely to have persistent problems.

  • 282.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Swedish Soc Oncol, Stockholm, Sweden.
    Cancer treatment of today in view of the Nobel Prize2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 205-206Article in journal (Other academic)
  • 283.
    Velders, Matthijs A.
    et al.
    Vastmanland Cty Hosp, Dept Med, Sigtunagatan, S-72189 Vasteras, Sweden.
    Calais, Fredrik
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Dahle, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Huddinge, Sweden.
    Tenerz, Åke
    Vastmanland Cty Hosp, Dept Med, Sigtunagatan, S-72189 Vasteras, Sweden.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, Vasteras, Sweden.
    Cathepsin D improves the prediction of undetected diabetes in patients with myocardial infarction2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 187-192Article in journal (Refereed)
    Abstract [en]

    Background: Newer therapeutic agents for type 2 diabetes mellitus can improve cardiovascular outcomes, but diabetes remains underdiagnosed in patients with myocardial infarction (MI). We sought to identify proteomic markers of undetected dysglycaemia (impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) to improve the identification of patients at highest risk for diabetes.

    Materials and methods: In this prospective cohort, 626 patients without known diabetes underwent oral glucose tolerance testing (OGTT) during admission for MI. Proximity extension assay was used to measure 81 biomarkers. Multivariable logistic regression, adjusting for risk factors, was used to evaluate the association of biomarkers with dysglycaemia. Subsequently, lasso regression was performed in a 2/3 training set to identify proteomic biomarkers with prognostic value for dysglycaemia, when added to risk factors, fasting plasma glucose, and glycated haemoglobin A1c. Determination of discriminatory ability was performed in a 1/3 test set.

    Results: In total, 401/626 patients (64.1%) met the criteria for dysglycaemia. Using multivariable logistic regression, cathepsin D had the strongest association with dysglycaemia. Lasso regression selected seven markers, including cathepsin D, that improved prediction of dysglycaemia (area under the receiver operator curve [AUC] 0.848 increased to 0.863). In patients with normal fasting plasma glucose, only cathepsin D was selected (AUC 0.699 increased to 0.704).

    Conclusions: Newly detected dysglycaemia, including manifest diabetes, is common in patients with acute MI. Cathepsin D improved the prediction of dysglycaemia, which may be helpful in the a priori risk determination of diabetes as a motivation for confirmatory OGTT.

  • 284.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Human neutrophil lipocalin (HNL) as a biomarker of acute infections2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 1-8Article, review/survey (Refereed)
    Abstract [en]

    The early and accurate discrimination between bacterial and viral causes of acute infections is the key to a better use of antibiotics and will help slow down the fast-growing resistance to commonly used antibiotics. This discrimination is in the vast majority of cases possible to achieve by blood assay of the biomarker human neutrophil lipocalin (HNL), which we showed to be uniquely increased in patients suffering from bacterial infections. In serum, sensitivities and specificities of >90% are achieved in both adults and children. In order to eliminate the need to produce serum, a whole-blood assay with an assay time of <10 min was developed in which blood neutrophils are activated to release HNL. The diagnostic accuracy of this assay also showed sensitivities and specificities of >90% in most infectious diseases and was clearly superior to contemporary assays such as blood neutrophil counts, C-reactive protein, procalcitonin, and expression of CD64 on blood neutrophils. This format lends itself to the development of a point-of-care HNL assay and will be a major step forward to accomplish the goal of accurately diagnosing patients with symptoms of acute infections within 10 min at the emergency room or at the doctor's office.

  • 285.
    Vessby, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Järvi, Anette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Andersson, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Diet, Nutrition and Diabetes Mellitus2000In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 105, no 2, p. 151-160Article in journal (Refereed)
    Abstract [en]

    Nutritional management of diabetes mellitus, and the importance of diet in the development of insulin resistance, have for many years been important areas of research and education at the Unit for Clinical Nutrition Research at the Department of Public Health and Caring Sciences (formerly Department of Geriatrics) at Uppsala University. The research has more recently focussed on effects of dietary fat quality in the development of insulin resistance and in treatment of diabetes, on interaction between dietary fat and physical activity in relation to insulin sensitivity and on the importance of carbohydrate rich foods with low glycaemic index in the diabetic diet. Much work has also been directed towards development of educational material about nutrition recommendations and dietary treatment in diabetes mellitus. The ultimate goals for all oureffortsare to visualize, and promote, the possibilities and fundamental importance of lifestyle changes. This includes an improved diet and increased physical activity, in the prevention and treatment of diabetes mellitus.

  • 286. Vilhelmsdotter Allander, Susanne
    et al.
    Marké, Lars-Åke
    Wihlen, Björn
    Svensson, Maria
    Elinder, Carl-Gustaf
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Regional variation in use of exogenous and endogenous glomerular filtration rate (GFR) markers in Sweden2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 3, p. 273-278Article in journal (Refereed)
    Abstract [en]

    Background.

    Markers of renal function (glomerular filtration rate (GFR)) are frequently used in the Swedish health care. GFR is usually estimated based on plasma creatinine concentration, but plasma cystatin C concentration, creatinine clearance, iohexol clearance, and 51Cr-EDTA clearance are also used. These markers are all part of the daily patient care, but there is little specific information on the clinical use of these markers. The aim of this study was to compare the use of these various GFR markers in different parts of Sweden and potential changes over time.

    Methods.

    Retrospective study using questionnaires to collect information for the years 2006-2009 divided per county on the specific use of GFR markers with type of test reports.

    Results.

    Plasma/serum creatinine concentration (96%) is by far the dominating GFR marker in Sweden, while cystatin C concentration (3.5%), creatinine clearance (0.1%), iohexol clearance (0.1%), and 51Cr-EDTA clearance (0.1%) are less frequently used. The use of GFR markers, including creatinine, continues to increase on a national level with the exception of creatinine clearance and 51Cr-EDTA clearance. There were considerable variations between different counties in the use of GFR markers and the type of test reports that the laboratories provided.

    Conclusions.

    The inter-county variations of GFR markers used in Sweden are large and indicate that savings associated with optimized test utilization in this regard could be substantial. Regional habits and traditions are likely to influence the variations in GFR marker use.

  • 287.
    von Celsing, Anna-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Wallman, Thorne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Predicting return to work among sickness-certified patients in general practice: Properties of two assessment tools2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Abstract Aim. The purpose was to analyse the properties of two models for the assessment of return to work after sickness certification, a manual one based on clinical judgement including non-measurable information ('gut feeling'), and a computer-based one. Study population. All subjects aged 18 to 63 years, sickness-certified at a primary health care centre in Sweden during 8 months (n = 943), and followed up for 3 years. Methods. Baseline information included age, sex, occupational status, sickness certification diagnosis, full-time or part-time current sick-leave, and sick-leave days during the past year. Follow-up information included first and last day of each occurring sick spell. In the manual model all subjects were classified, based on baseline information and gut feeling, into a high-risk (n = 447) or a low-risk group (n = 496) regarding not returning to work when the present certificate expired. It was evaluated with a Cox's analysis, including time and return to work as dependent variables and risk group assignment as the independent variable, while in the computer-based model the baseline variables were entered as independent variables. Results. Concordance between actual return to work and return to work predicted by the analysis model was 73%-76% during the first 28-180 days in the manual model, and approximately 10% units higher in the computer-based model. Based on the latter, three nomograms were constructed providing detailed information on the probability of return to work. Conclusion. The computer-based model had a higher precision and gave more detailed information than the manual model.

  • 288.
    Von Zur-Mühlen, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadstrom, Jonas
    Single-centre long-term follow-up of live kidney donors demonstrates preserved kidney function but the necessity of a structured lifelong follow-up2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 236-241Article in journal (Refereed)
    Abstract [en]

    Background. The increase of live kidney donation (LKD) demands that we scrutinize its long-term consequences. Socialized medicine in Sweden has allowed us to survey long-term consequences of LKD with a high response rate. Methods. Between 1974 and 2008, 455 LKDs were performed; 28 donors were deceased and 14 had moved abroad at the time of the survey. Of the remaining 413, 96% agreed to participate in a retrospective study with laboratory testing and answering a questionnaire. Results. Mean age at donation was 49 +/- 10 years, and the mean time since nephrectomy was 11 +/- 7 years (range 1-33). No death was of renal cause. S-creatinine at follow-up was 93 +/- 18 mu mol/L, 28% had treated hypertension, of whom only 52% had BP <140/90. Eleven per cent had spot microalbuminuria, and 1% were diagnosed with diabetes mellitus. Seventy-one per cent had check-ups at least every second year, but 14% had no check-ups. Eighty per cent would be willing to donate again if it were possible, and only 3% regretted the donation. Conclusion. Renal function is well preserved in the long term after donation, no case of end-stage renal disease was identified, and a large majority of our donors would donate again if it were possible. Although rates of microalbuminuria and hypertension were at expected levels, a significant number of donors demonstrated elevated blood pressure levels and inadequate antihypertensive treatment. A relatively large number of donors did not receive regular check-ups. Both of these issues demonstrate the need for a better-structured lifelong follow-up.

  • 289.
    Vægter, Keld
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Wahlström, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    General practitioners' awareness of their own drug prescribing profiles after postal feedback and outreach visits2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 4, p. 439-444Article in journal (Refereed)
    Abstract [en]

    Background. General practice accounts for the vast majority of drug prescribing in the Nordic countries. Various methods have been used to promote rational drug prescribing. Awareness of own prescribing profile may be a first crucial step in the quality assessment and improvement process. Aim of the study. To analyse awareness among general practitioners of their drug prescribing profile during two outreach visits one year apart. Methods. All 94 practices with a total of 166 general practitioners in the former Storstrom County, Denmark, were invited to participate in a project launching outreach visits led by a general practitioner; 88 practices with 160 general practitioners agreed to participate. Results. During the first round of outreach visits the general practitioners were asked to rate their own prescribing level of 13 major drug groups as being in the lowest 25%, the middle 26%74%, or the highest 25% of the distribution across all 88 practices. The result was better than chance (chi-square 337, 4 df, r 0.37, both P < 0.0001). After the assessment a one-hour discussion on rational drug prescribing was held. One year later a new round of outreach visits was held. This time the assessment accuracy was generally greatly improved (chi-square 724, 4 df, r 0.48, both P < 0.0001). The main determinants for the improved accuracy during the second round were high accuracy during the first round, and the number of general practitioners in the practice. Conclusions. General practitioners' awareness of their prescribing volumes was substantially improved by a single outreach visit with discussion on rational drug prescribing.

  • 290.
    Vægter, Keld
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Wahlström, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Wedel, Hans
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Effect of mailed feedback on drug prescribing profiles in general practice: a seven-year longitudinal study in Storstrom County, Denmark2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 4, p. 238-244Article in journal (Refereed)
    Abstract [en]

    Background. Whether written feedback on drug prescribing in general practice affects prescribing habits is controversial. Most short-term studies showed no effect. However, the issue has not been tested in long-term studies involving the local general practitioner community. Aims of the study. To assess whether prescribing levels in general practice are affected by long-term, unsolicited, systematically repeated, mailed feedback. Methods. Each of the 94 general practices in Storstrom County, Denmark, received semi-annual, mailed feedback about their prescribing volumes and costs within 13 major drug groups, in relation to the levels for all the other 93 practices over a 7-year period in a project initiated by the local general practitioner association. Data on the number of defined daily doses (DDDs) prescribed per 1000 listed patients in each practice per 6-months, and practice characteristics, were obtained from the Pharmaceutical Database at the County Health Department. Results. There was a large variation in drug prescribing volume between practices, but little within-practice variation over time. After adjustments for the influence of practice size and other potential outcome-affecting variables, there was no evidence of a general change of prescribing volume over time, no change among practices with a high or a low prescribing level, and no significant change within the various drug groups. Conclusions. We found no significant effects on prescribing levels of mailed feedback, even when repeated semi-annually during 7 years and initiated by the local general practitioner community.

  • 291.
    Wahlberg, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Erikson, Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Fuchs, Laszlo
    Andersson, Anders
    Attefall, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Dosin--a new pump device. Its construction and function2007In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 112, no 1, p. 83-93Article in journal (Refereed)
    Abstract [en]

    The cyclic flow of the Dosin(R) is useful in interventional radiology since it prevents clotting and increases the mixing with the blood. The flow rate varies from 0.03 mL/s to 5 mL/s and it is recommended to use fluid with a viscosity lower than 3 mPa.s. The outlet pressure is recommended below 300 mm Hg. The Dosin(R) must be replaced after each patient, alternatively after maximum 24h continuous use.

  • 292. Wahlberg, Andreas
    et al.
    Eriksson, Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Attefall, Anna
    Andersson, Anders
    Gastrointestinal radiological investigations with a new pump device: experimental and clinical experiences2008In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 113, no 1, p. 73-78Article in journal (Refereed)
    Abstract [en]

    In an earlier paper a new pump device for medical applications was described. This enabled a continuous flow of saline, barium contrast agent and gases. We now report further study of this device: The use of gases was experimentally studied to give a basis for use in CT-colonography. We also report experiences from injection of barium contrast agent via a naso-duodenal tube for radiological investigation of the small intestine in patients with gastrointestinal suffering. The radiation exposure to the x-ray staff was reduced. The investigation procedure was standardised and shortened.

  • 293.
    Walfridsson, Angelica
    et al.
    Ostervala Primary Hlth Care Ctr, Ostervala, Sweden..
    Sehlberg, Maja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gillespie, Ulrika
    Uppsala Univ Hosp Akad Sjukhuset, Uppsala, Sweden..
    Dahlkvist, Jonathan
    Uppsala Lans Landsting, Uppsala, Sweden..
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Ostervala Primary Hlth Care Ctr, Ostervala, Sweden..
    Diabetes treatment and hypoglycaemic episodes in elderly patients at nursing homes in Uppsala County2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 179-183Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to examine the situation for elderly patients with diabetes living in nursing homes with regard to diabetes treatment, clinical variables, and vascular complications associated with diabetes. A second aim was to evaluate if the patients were at risk of hypoglycaemia. Methods: This was a cross-sectional study including diabetes patients from all 30 nursing homes in Uppsala County, Sweden. Current antidiabetic medications, HbA(1c) hypoglycaemic events, and diabetes complications were registered from the medical records. The patients were stratified into a general group and divided into three groups according to HbA(1c) (<52, 52-73, and >73 mmol/mol). Results: Of 1,350 individuals, 218 patients were identified with diabetes mellitus. The diabetes duration was 11.2 +/- 9.4 years and their serum HbA(1c) concentration 56.0 +/- 1.2 mmol/mol. Hypoglycaemic events were reported in 24% of the diabetic individuals, and 43.1% of them had HbA(1c) <52 mmol/mol (mean value 44.0 +/- 1.1 mmol/mol). Of these, 36% were taking antidiabetic drugs. Another 35.8% of the patients had HbA(1c) values between 52-73 mmol/mol (mean value 60.0 +/- 1.1 mmol/mol), and 82% of these patients were taking antidiabetic drugs. Almost 80% of the diabetic patients had either micro- or macrovascular complications, with diabetes duration as an association for both micro- or macrovascular complications and hypoglycaemic events. Conclusions: A reduction of the use of antidiabetic drugs with follow-up of HbA(1c) level should be considered, especially for multimorbid elderly patients with low HbA(1c) and hypoglycaemia.

  • 294.
    Wallentin, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Uppsala Clinical Research Center: development of a platform to promote national and international clinical science2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Uppsala Clinical Research Center (UCR) is a non-profit organization that provides service for clinical research aiming for development and improvement of health care in Sweden and worldwide. UCR was started in 2001 with the ambition to shift the focus of clinical research from new medications or devices launched by the industry to problem-based research on issues identified in clinical reality, for example through the national quality registries. In order to accomplish these goals, UCR has established services in: 1) clinical trials of new and old methods in health care; 2) quality development of the health care system supported by internet-based national quality registries; 3) biostatistics, epidemiology, and data management; 4) biobanking of biological materials (Uppsala Biobank); 5) high-throughput biochemical analyses (UCR laboratory); and 6) academic leadership by the members of the UCR research faculty. The UCR clinical trials group provides services for investigator-driven projects in all areas of health care, for global mega-trials on new pharmaceutical treatments and devices, for biobanking including biomarker and genetics analyses, and for clinical events adjudication in national as well as global mega-trials. During the last few years, UCR has been a pioneer in establishing the registry-based randomized clinical trial (R-RCT), which today is an international model on how to perform cost-effective pragmatic randomized trials in the real-world environment. In 2002, UCR started the first national competence center for national quality registries, which pioneered the development of the current internet-based technologies for registering, reporting, and supporting continuous systematic improvement of health care. UCR is currently harboring around 20 national quality registries in all areas of health care. Today, UCR is the leading European center for registry-based quality development and evaluation of new medical treatments in cardiovascular care and has started to support other European countries in implementing the UCR registry platform in order to improve quality of care in the European Union.

  • 295.
    Wallén-Mackenzie, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Wootz, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Englund, Hillevi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Genetic inactivation of the vesicular glutamate transporter 2 (VGLUT2) in the mouse: what have we learnt about functional glutamatergic neurotransmission?2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, p. 11-20Article, review/survey (Refereed)
    Abstract [en]

    During the past decade, three proteins that possess the capability of packaging glutamate into presynaptic vesicles have been identified and characterized. These three vesicular glutamate transporters, VGLUT1-3, are encoded by solute carrier genes Slc17a6-8. VGLUT1 (Slc17a7) and VGLUT2 (Slc17a6) are expressed in glutamatergic neurons, while VGLUT3 (Slc17a8) is expressed in neurons classically defined by their use of another transmitter, such as acetylcholine and serotonin. As glutamate is both a ubiquitous amino acid and the most abundant neurotransmitter in the adult central nervous system, the discovery of the VGLUTs made it possible for the first time to identify and specifically target glutamatergic neurons. By molecular cloning techniques, different VGLUT isoforms have been genetically targeted in mice, creating models with alterations in their glutamatergic signalling. Glutamate signalling is essential for life, and its excitatory function is involved in almost every neuronal circuit. The importance of glutamatergic signalling was very obvious when studying full knockout models of both VGLUT1 and VGLUT2, none of which were compatible with normal life. While VGLUT1 full knockout mice die after weaning, VGLUT2 full knockout mice die immediately after birth. Many neurological diseases have been associated with altered glutamatergic signalling in different brain regions, which is why conditional knockout mice with abolished VGLUT-mediated signalling only in specific circuits may prove helpful in understanding molecular mechanisms behind such pathologies. We review the recent studies in which mouse genetics have been used to characterize the functional role of VGLUT2 in the central nervous system.

  • 296.
    Wang, Eugen Y-H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Eriksson, Hans G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Quality of life and functional outcomes 10 years after laparoscopic radical prostatectomy2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    Background.

    Minimally invasive laparoscopic radical prostatectomy (LRP) has proven equally effective as open surgery in terms of cancer control and peroperative complication rate with less bleeding and postoperative pain. However, long-term follow-up data after LRP are scarce, especially as related to quality of life (QoL).

    Aim.

    To compare QoL and functional outcomes at least 10 years after LRP with a population-based control group matched for age and region.

    Methods.

    Follow-up data were obtained by mailed questionnaires from patients who responded anonymously to five international questionnaires (EQ-5D, QLQ-C30, QLQ-PR25, IPSS, and IIEF). We collected self-reported outcome data directly from 49 patients who underwent LRP more than 10 years ago in our centre. The results of the patients' overall QoL and urinary continence rates were compared with 918 controls matched for region and age.

    Results.

    Forty-two patients (86%) and 808 (88%) controls reported having no urinary leakage. Only 11 patients (24%) still had sexual activities 10 years after LRP, and three were without erectile dysfunction. There was no difference in four of five statements of the self-assessed QoL questionnaires between the LRP and control group. Anxiety level was higher in the LRP group (44%) than in the control group (23%).

    Conclusion.

    Patients reported high self-assessed QoL, although they also reported low sexual activity 10 years after LRP. Prevalence of urinary leakage was similar in both groups. However, anxiety was more common in LRP patients.

  • 297.
    Wang, Xuan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bcl-2 maintains the mitochondrial membrane potential, but fails to affect production of reactive oxygen species and endoplasmic reticulum stress, in sodium palmitate-induced beta-cell death2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 4, p. 306-315Article in journal (Refereed)
    Abstract [en]

    Background. Sodium palmitate causes apoptosis of beta-cells, and the anti-apoptotic protein Bcl-2 has been shown to counteract this event. However, the exact mechanisms that underlie palmitate-induced pancreatic beta-cell apoptosis and through which pathway Bcl-2 executes the protective effect are still unclear. Methods. A stable Bcl-2-overexpressing RINm5F cell clone (BMG) and its negative control (B45) were exposed to palmitate for up to 8 h, and cell viability, mitochondrial membrane potential (Delta psi m), reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, and NF-kappa B activation were studied in time course experiments. Results. Palmitate exposure for 8 h resulted in increased cell death rates, and this event was partially counteracted by Bcl-2. Bcl-2 overexpression promoted in parallel also a delayed induction of GADD153/CHOP and a weaker phosphorylation of BimEL in palmitate-exposed cells. At earlier time points (2-4 h) palmitate exposure resulted in increased generation of ROS, a decrease in mitochondrial membrane potential (Delta psi m), and a modest increase in the phosphorylation of eIF2 alpha and IRE1 alpha. BMG cells produced similar amounts of ROS and displayed the same eIF2 alpha and IRE1 alpha phosphorylation rates as B45 cells. However, the palmitate-induced dissipation of Delta psi m was partially counteracted by Bcl-2. In addition, basal NF-kappa B activity was increased in BMG cells. Conclusions. Our results indicate that Bcl-2 counteracts palmitate-induced beta-cell death by maintaining mitochondrial membrane integrity and augmenting NF-kappa B activity, but not by affecting ROS production and ER stress.

  • 298.
    Wargelius, Hanna-Linn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fahlke, Claudia
    Suomi, Stephen J.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Higley, James Dee
    Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, p. 49-55Article in journal (Refereed)
    Abstract [en]

    Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.

  • 299.
    Welsh, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Claes Hellerström and Cartesian Diver respirometry2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 2, p. 77-80Article in journal (Refereed)
    Abstract [en]

    Cartesian diver microrespirometry was introduced by Claes Hellerström at the Department of Histology/Medical Cell Biology at Uppsala University, Sweden, to determine rates of oxygen consumption in islets of Langerhans. The theory behind this method is touched upon and the main findings described. Glucose-stimulated beta cell respiration significantly contributes to increased ATP generation, which is a prerequisite for stimulated insulin secretion and synthesis. This has had major implications for understanding the beta cell stimulus secretion coupling.

  • 300.
    Welsh, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Annerén, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lindholm, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kriz, Vitezslav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Öberg-Welsh, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Role of tyrosine kinase signaling for beta-cell replication and survival2000In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 105, no 2, p. 7-15Article in journal (Refereed)
    Abstract [en]

    Diabetes mellitus is commonly considered as a disease of a scant beta-cell mass that fails to respond adequately to the functional demand. Tyrosine kinases may play a role for beta-cell replication, differentiation (neoformation) and survival. Transfection of beta-cells with DNA constructs coding for tyrosine kinase receptors yields a ligand-dependent increase of DNA synthesis in beta-cells. A PCR-based technique was adopted to assess the repertoire of tyrosine kinases expressed in fetal islet-like structures, adult islets or RINm5F cells. Several tyrosine kinase receptors, such as the VEGFR-2 (vascular endothelial growth factor receptor 2) and c-Kit, were found to be present in pancreatic duct cells. Because ducts are thought to harbor beta-cell precursor cells, these receptors may play a role for the neoformation of beta-cells. The Src-like tyrosine kinase mouse Gtk (previously named Bsk/Iyk) is expressed in islet cells, and was found to inhibit cell proliferation. Furthermore, it conferred decreased viability in response to cytokine exposure. Shb is a Src homology 2 domain adaptor protein which participates in tyrosine kinase signaling. Transgenic mice overexpressing Shb in beta-cells exhibit an increase in the neonatal beta-cell mass, an improved glucose homeostasis, but also decreased survival in response to cytokines and streptozotocin. It is concluded that tyrosine kinase signaling may generate multiple responses in beta-cells, involving proliferation, survival and differentiation.

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