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| 5. |
- Lindblom, P, et al.
(author)
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Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies
- 2012
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In: Toxicologic pathology. - : SAGE Publications. - 1533-1601 .- 0192-6233. ; 40:1, s. 18-32
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Journal article (peer-reviewed)abstract
- Tesaglitazar was developed as a dual peroxisome proliferator–activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.
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| 9. |
- Johansson, A, et al.
(author)
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Increased frequency of a new polymorphism in the cycle 2 (cdc2) gene in patients with Alzheimer's disease frontotemporal dementia
- 2003
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In: Neuroscience Letters. - 0304-3940. ; 340:1, s. 69-73
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Journal article (peer-reviewed)abstract
- Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6 + 7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6 + 7II genotype. Our findings suggest that the Ex6 + 7I allele is associated with tauopathies, both AD and FrD. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 11. |
- Olalde, I., et al.
(author)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
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Journal article (peer-reviewed)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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| 13. |
- Volpe, C, et al.
(author)
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The role of adrenal scintigraphy in the preoperative management of primary aldosteronism
- 2008
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In: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1457-4969. ; 97:3, s. 248-253
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Journal article (peer-reviewed)abstract
- Differentiation between the two major subgroups of primary aldosteronism, bilateral hyperplasia and aldosterone producing adenoma is essential since therapy in the former is medical and in the latter surgical. The aim of the present study was to evaluate the clinical utility of adrenocortical scintigraphy in the management of primary aldosteronism. Material and Methods: [131I] norcholesterol (NP-59) scintigraphy with dexamethasone suppression for subclassification and lateralization of primary aldosteronism was evaluated in 49 patients with long-term follow-up after diagnosis and treatment Results: Thirty-three patients with the diagnosis of aldosterone producing adenoma were operated with adrenalectomy. Preoperative scintigraphy showed lateralized isotope uptake in 27/33 patients while 6 showed no uptake. Twenty-two were cured and three significantly improved. Thus, in 25/33 (76%), scintigraphy showed the correct side as the patients benefited of surgery. Two patients did not improve. Fourteen patients with a probable diagnosis of bilateral hyperplasia had normal scintigraphies. Conclusions: In the present retrospective study we found limited sensitivity of NP-59 scintigraphy. However, when a lateralized scintigraphic uptake is achieved it has a high accuracy. Scintigraphy may be used as an adjunct in cases where adrenal venous sampling is inconclusive.
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| 15. |
- Albert, F, et al.
(author)
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Laser produced X-ray source in the 10-60 keV range at 1 kHz. Modified irradiation schemes in order to reach medical imaging quality
- 2001
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In: Journal de Physique IV. - : EDP Sciences. - 1155-4339. ; 11:PR2, s. 429-432
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Journal article (peer-reviewed)abstract
- By tightly focusing ultra-short pulses from a Ti:sapphire terawatt laser onto a high-Z metallic target, hard x-ray pulses of short duration are produced. In most of our previous work concerning x-rays, a 150 mJ laser pulse with a 110 A duration has been used. Using mostly tin and tantalum targets, hard x-rays in the 10-60 keV range have been produced and used in differential absorption imaging around the K-alpha absorption edge of a contrast agent and also in imaging employing gated viewing for suppression of scattered radiation. In order to increase the x-ray yield (shortening the acquisition time) an increase in the laser repetition rate is desirable while still staying in the K-alpha energy regime. We have used a I kHz repetition-rate laser delivering 35 fs pulses in order to work towards these goals. We have clear evidence of hard x-ray generation above 30 keV, even for low laser pulse energies. We also studied the effect of a fs prepulse. The medical imaging capability of the source was explored. The use of a prepulse has been optimized in order to improve the image quality as well as the overall x-ray generation yield.
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| 16. |
- Andersson, L., et al.
(author)
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Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in the Swedish hard metal industry, in particular to cobalt
- 2021
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In: Biomarkers. - : Informa UK Limited. - 1354-750X .- 1366-5804. ; 26:6
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Journal article (peer-reviewed)abstract
- Purpose To study the relationship between inhalation of airborne particles and cobalt in the Swedish hard metal industry and markers of inflammation and coagulation in blood. Methods Personal sampling of inhalable cobalt and dust were performed for subjects in two Swedish hard metal plants. Stationary measurements were used to study concentrations of inhalable, respirable, and total dust and cobalt, PM10 and PM2.5, the particle surface area and the particle number concentrations. The inflammatory markers CC16, TNF, IL-6, IL-8, IL-10, SAA and CRP, and the coagulatory markers FVIII, vWF, fibrinogen, PAI-1 and D-dimer were measured. A complete sampling was performed on the second or third day of a working week following a work-free weekend, and additional sampling was taken on the fourth or fifth day. The mixed model analysis was used, including covariates. Results The average air concentrations of inhalable dust and cobalt were 0.11 mg/m(3) and 0.003 mg/m(3), respectively. For some mass-based exposure measures of cobalt and total dust, statistically significant increased levels of FVIII, vWF and CC16 were found. Conclusions The observed relationships between particle exposure and coagulatory biomarkers may indicate an increased risk of cardiovascular disease.
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| 21. |
- Edquist, Charles, et al.
(author)
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Characteristics of collaboration in product innovation in the regional system of innovation of East Gothia
- 2002
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In: European Planning Studies. - : Informa UK Limited. - 0965-4313 .- 1469-5944. ; 10:5, s. 563-582
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Journal article (peer-reviewed)abstract
- The focus of this article is on product innovations introduced by firms (establishments) and the collaborations they enter into with other firms and organizations in carrying out this activity. The theoretical framework combines innovation theories with the literature on regional innovation systems and the knowledge-based economy. Empirically we have investigated characteristics of collaboration among manufacturing establishments in the region of East Gothia in Sweden, with specific focus on the number of employees involved in the innovation projects, mechanisms of knowledge transfer between organizations, as well as financing and patenting in relation to product innovations.
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| 24. |
- Ejegard, H, et al.
(author)
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Sexuality after delivery with episiotomy: a long-term follow-up
- 2008
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In: Gynecologic and obstetric investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 66:1, s. 1-7
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Journal article (peer-reviewed)abstract
- <i>Aim:</i> To investigate the quality of women’s sex life 12–18 months after first, episiotomy-assisted childbirth and risk factors for long-term dyspareunia after childbirth. <i>Methods:</i> Two hundred and six women who gave birth vaginally at the Karolinska University Hospital between September 1997 and February 1998 and from June 1998 to January 1999 received postal questionnaires at 12–18 months postpartum. Obstetrical, psychological and sexological data, concerning 110 primiparae who underwent episiotomy and 153 age-matched women who did not, were compared. Possible risk factors for postpartum dyspareunia were investigated in the entire sample. <i>Results:</i> Women who underwent episiotomy experienced a more complicated and emotionally difficult delivery. They reported a higher frequency of dyspareunia and insufficient lubrication than women who had given birth without episiotomy. Arousal, orgasm and satisfaction with sex were not affected. Episiotomy, perineal lacerations, fundal pressure at delivery and a history of dyspareunia were independent risk factors for dyspareunia 12–18 months postpartum. <i>Conclusion:</i> Episiotomy may affect women’s sex life during the second year post partum with more frequent pain and vaginal dryness at intercourse. Other obstetrical factors and pain history may also influence the propensity for dyspareunia.
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| 27. |
- Fleck, Tatjana, et al.
(author)
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The management of deep sternal wound infections using vacuum assisted closure (V.A.C.) therapy
- 2006
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In: International Wound Journal. - 1742-481X. ; 3:4, s. 273-280
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Journal article (peer-reviewed)abstract
- A group of international experts met in May 2006 to develop clinical guidelines on the practical application of vacuum assisted closure (V.A.C.)+ therapy in deep sternal wound infections. Group discussion and an anonymous interactive voting system were used to develop content. The recommendations are based on current evidence or, where this was not available, the majority consensus of the international group. The principles of treatment for deep sternal wound infections include early recognition and treatment of infection. V.A.C. therapy should be instigated early, following thorough wound irrigation and surgical debridement. V.A.C. therapy in deep sternal wound infections requires specialist surgical supervision and should only be undertaken by clinicians with adequate experience and training in the use of the technique.
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| 28. |
- Garkavij, Michael, et al.
(author)
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Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats
- 1994
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In: Journal of nuclear biology and medicine (Turin, Italy : 1991). - 0368-3249. ; 38:4, s. 594-600
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Journal article (peer-reviewed)abstract
- In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.
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| 29. |
- Geneid, A., et al.
(author)
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Union of the European Phoniatricians position statement on the exit strategy of phoniatric and laryngological services: staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020)
- 2020
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In: Journal of Laryngology and Otology. - : CAMBRIDGE UNIV PRESS. - 0022-2151 .- 1748-5460. ; 134:8, s. 661-664
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Journal article (peer-reviewed)abstract
- Background The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. Objectives This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. Conclusion As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.
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| 32. |
- Hayden, JA, et al.
(author)
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Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials
- 2020
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In: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 54:21, s. 1277-
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Journal article (peer-reviewed)abstract
- Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise.MethodsIn parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers.ResultsWe received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) −10.7 (−14.1 to –7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) −10.2 (−13.2 to –7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers—these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics.ConclusionsThis study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups.Protocol publicationhttps://doi.org/10.1186/2046-4053-1-64
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| 40. |
- Ofverholm, I. Ivanov, et al.
(author)
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PROGNOSTIC IMPACT OF IKZF1 DELETIONS IN PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA TREATED ACCORDING TO NOPHO PROTOCOLS - THE SWEDISH EXPERIENCE
- 2014
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In: Haematologica. - 0390-6078 .- 1592-8721. ; 99:Suppl 1, s. 9-9
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Journal article (other academic/artistic)abstract
- Recently, IKZF1 deletions have been shown to be associated notonly with the leukemogenic process but also to confer a poor prognosis in allrisk groups of B-cell precursor ALL. In a previous study, we used Multiplex Ligation-dependentProbe Amplification (MLPA) to investigate the presence ofIKZF1 deletions in bone marrow DNA from 116 children diagnosed with BCPALL in a single center and treated according to NOPHO protocols. Deletionswere detected in 16% of cases; both event free survival and overall survivalwere significantly reduced in the IKZF1-deleted group compared to the groupwith intact IKZF1.
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| 42. |
- Olsson, A, et al.
(author)
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Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
- 2003
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In: Experimental Neurology. - 0014-4886. ; 183, s. 74-
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Journal article (peer-reviewed)abstract
- One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 43. |
- Olsson, Sandra, 1976, et al.
(author)
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Genetic Variation Within the Interleukin-1 Gene Cluster and Ischemic Stroke
- 2012
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In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:9
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Journal article (peer-reviewed)abstract
- Background and Purpose-Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to investigate whether genetic variation in the interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes (IL1A, IL1B, and IL1RN) is associated with IS and/or any etiologic subtype of IS. Methods-Twelve tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 844 patients with IS and 668 control subjects. IS subtypes were defined according to the Trial of Org 10172 in Acute Stroke Treatment criteria in SAHLSIS. The Lund Stroke Register and the Malmo Diet and Cancer study were used as a replication sample for overall IS (in total 3145 patients and 1793 control subjects). Results-The single nucleotide polymorphism rs380092 in IL1RN showed an association with overall IS in SAHLSIS (OR, 1.21; 95% CI, 1.02-1.43; P = 0.03), which was replicated in the Lund Stroke Register and the Malmo Diet and Cancer study sample. An association was also detected in all samples combined (OR, 1.12; 95% CI, 1.04 -1.21; P = 0.03). Three single nucleotide polymorphisms in IL1RN (including rs380092) were nominally associated with the subtype of cryptogenic stroke in SAHLSIS, but the statistical significance did not remain after correction for multiple testing. Furthermore, increased plasma levels of interleukin-1 receptor antagonist were observed in the subtype of cryptogenic stroke compared with controls. Conclusion-This comprehensive study, based on a tagSNP approach and replication, presents support for the role of IL1RN in overall IS. (Stroke. 2012; 43: 2278-2282.)
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