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- Høyer, B B, et al.
(författare)
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Body mass index in young school age children in relation to organochlorine compounds in early life: a prospective study.
- 2014
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 38:7, s. 919-925
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To investigate the association between maternal pregnancy and estimated postnatal serum concentrations of the organochlorines 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and body mass index (BMI) z-scores in five to nine-year-old children.Methods:Maternal sera from the INUENDO birth cohort (2002-2004) comprising mother-child pairs (N=1109) from Greenland, Warsaw (Poland) and Kharkiv (Ukraine) were analysed for CB-153 and p,p'-DDE, using gas chromatography-mass-spectrometry, and were grouped into tertiles for statistical analyses. A toxicokinetic model was used to estimate the first 12 months cumulative exposure to the compounds. Associations between these compounds and child age- and sex-specific BMI z-scores were calculated at follow-up (2010-2012), using multiple linear regression analysis.Results:No clear associations between pregnancy CB-153 and p,p'-DDE and child BMI were observed (the pooled differences in BMI z-score (95% confidence interval) comparing 3rd tertile to 1st tertile were -0.07 (-0.32 to 0.18) and -0.10 (-0.30 to 0.10) kg m(-2), respectively). For postnatal CB-153 and p,p'-DDE and BMI, the overall differences in BMI z-score comparing 3rd tertile to 1st tertile were 0.12 (-0.15 to 0.39) and -0.03 (-0.20 to 0.27) kg m(-2), respectively.Conclusions:This follow-up study of Greenlandic, Polish and Ukrainian populations showed no clear association between pregnancy and postnatal exposure to p,p'-DDE and CB-153 and BMI at the age of five to nine years.International Journal of Obesity accepted article peview online, 10 April 2014; doi:10.1038/ijo.2014.58.
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- Høyer, Birgit Bjerre, et al.
(författare)
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Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function : a Systematic Review of Human Evidence
- 2018
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Ingår i: Current Environmental Health Reports. - : Springer Science and Business Media LLC. - 2196-5412. ; 5:1, s. 20-33
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. RECENT FINDINGS: Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.
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- Kliest, Tessa, et al.
(författare)
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Clinical trials in pediatric ALS: a TRICALS feasibility study
- 2022
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
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| 8. |
- Magnusson, Yvonne, 1957, et al.
(författare)
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Antigenic analysis of the second extra-cellular loop of the human beta-adrenergic receptors.
- 1989
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Ingår i: Clinical and experimental immunology. - 0009-9104. ; 78:1, s. 42-8
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Tidskriftsartikel (refereegranskat)abstract
- Polyclonal antibodies were raised in rabbits by immunization with free peptides corresponding to positions 197-222 of the human beta 1-adrenergic receptor (beta 1 peptide) and the corresponding sequence (172-197) of the human beta 2-adrenergic receptor (beta 2 peptide). While the beta 2 peptide yielded antibodies that cross-reacted with the beta 1 peptide, the antibodies against the beta 1 peptide did not cross-react with the beta 2 sequence. Cross-reactivity of the anti-beta 2 peptide antibodies and the selectivity of the anti-beta 1 peptide antibodies were also revealed in the recognition by immunoblots of the beta 1- and beta 2-adrenergic receptors of different species or of the receptor gene products expressed in a bacterial vector. These antibodies could be used immunohistochemically to visualize the beta-adrenergic receptors on rabbit heart. The anti-beta 2 peptide antibodies did not show any functional effect on the beta-adrenergic receptors; the anti-beta 1 peptide antibodies were able to displace agonist affinity to higher values. Recognition of truncated peptides by the anti-beta 1 and anti-beta 2 peptide antibodies suggested that the cross-reaction of the anti-beta 2 peptide antibodies was due to the recognition of a common epitope on the C-terminal part of the peptides. The anti-beta 1 peptide antibodies recognized the N-terminal part of the peptide better than the C-terminal part. These results suggest that the second extracellular loop postulated in the structure of the human beta-adrenergic receptor contains the T and B cell epitopes necessary for induction of an immune response. The selectivity and the functional properties of the antibodies raised against that loop in the beta 1 adrenergic receptor could have relevance in induction of auto antibodies in certain cardiomyopathic conditions.
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- Olsson, Caroline, 1970, et al.
(författare)
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Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer.
- 2014
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Ingår i: Physics in medicine and biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 59:14, s. 3749-3759
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Tidskriftsartikel (refereegranskat)abstract
- When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.
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| 10. |
- Sørensen, Brita S., et al.
(författare)
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Does uncertainty in variability in relative biological effectiveness affect patient treatment in proton therapy?
- 2021
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 163, s. 177-184
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Forskningsöversikt (refereegranskat)abstract
- Clinical treatment with protons uses the concept of relative biological effectiveness (RBE) to convert the absorbed dose into an RBE-weighted dose that equals the dose for radiotherapy with photons causing the same biological effect. Currently, in proton therapy a constant RBE of 1.1 is generically used. However, empirical data indicate that the RBE is not constant, but increases at the distal edge of the proton beam. This increase in RBE is of concern, as the clinical impact is still unresolved, and clinical studies demonstrating a clinical effect of an increased RBE are emerging. Within the European Particle Therapy Network (EPTN) work package 6 on radiobiology and RBE, a workshop was held in February 2020 in Manchester with one day of discussion dedicated to the impact of proton RBE in a clinical context. Current data on RBE effects, patient outcome and modelling from experimental as well as clinical studies were presented and discussed. Furthermore, representatives from European clinical proton therapy centres, who were involved in patient treatment, laid out their current clinical practice on how to consider the risk of a variable RBE in their centres. In line with the workshop, this work considers the actual impact of RBE issues on patient care in proton therapy by reviewing pre clinical data on the relation between linear energy transfer (LET) and RBE, current clinical data sets on RBE effects in patients, and applied clinical strategies to manage RBE uncertainties. A better understanding of the variability in RBE would allow development of proton treatments which are safer and more effective.
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