| 1. |
- Hebebrand, J., et al.
(författare)
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A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk
- 2017
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Ingår i: Obesity Facts. - : S. Karger AG. - 1662-4025 .- 1662-4033. ; 10:4, s. 284-307
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Tidskriftsartikel (refereegranskat)abstract
- Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way. (C) 2017 The Author(s) Published by S. Karger GmbH, Freiburg
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| 2. |
- Barregård, L, et al.
(författare)
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Cadmium, mercury, and lead in kidney cortex of the general Swedish population: a study of biopsies from living kidney donors.
- 1999
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Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 107:11, s. 867-71
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Tidskriftsartikel (refereegranskat)abstract
- Cadmium, mercury, and lead concentrations were determined in deep-frozen kidney cortex biopsies taken from 36 living, healthy Swedish kidney donors (18 males and 18 females), who were 30-71 (mean 53) years of age. Information about occupation, smoking, the presence of dental amalgam, and fish consumption could be obtained for 27 of the donors. The samples (median dry weight 0.74 mg) were analyzed using inductively coupled plasma mass spectrometry, and the results were transformed to wet-weight concentrations. The median kidney Cd was 17 micrograms/g (95% confidence interval, 14-23 micrograms/g), which was similar in males and females. In 10 active smokers, the median kidney Cd was 24 micrograms/g, and in 12 who never smoked, it was 17 micrograms/g. The median kidney Hg was 0.29 micrograms/g, with higher levels in females (median 0.54 micrograms/g) than in males (median 0.16 micrograms/g). Subjects with amalgam fillings had higher kidney Hg (median 0.47 micrograms/g, n = 20) than those without dental amalgam (median 0.15 micrograms;g/g, n = 6), but kidney Hg was below the detection limit in some samples. Nearly half of the samples had kidney Pb below the detection limit. The median kidney Pb was estimated as 0. 14 micrograms/g. This is the first study of heavy metals in kidney cortex of living, healthy subjects, and the results are relatively similar to those of a few previous autopsy studies, indicating that results from autopsy cases are not seriously biased in relation to kidney metal concentrations in the general population. Cd concentrations in those who never smoked were relatively high, indicating considerable Cd intake from the diet in Sweden. The effect of dental amalgam on kidney Hg was as expected, although the reason for the difference in Hg levels between males and females is unclear.
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| 3. |
- Hallgren, C G, et al.
(författare)
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Markers of high fish intake are associated with decreased risk of a first myocardial infarction
- 2001
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 86:3, s. 397-404
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Tidskriftsartikel (refereegranskat)abstract
- High intake of fish has been associated with reduced risk of CHD. The high content of n-3 polyunsaturated fatty acids (PUFA) in fish has been suggested to be a protective factor. In addition, fish is the entirely dominating source of methylmercury for the general population, and the concentration of Hg in erythrocytes (Ery-Hg) is often used as an index of fish consumption. Our aim was to study the relationships between a first-ever myocardial infarction, Ery-Hg, activity of gluthathione peroxidase in erythrocytes (Ery-GSH-Px) and plasma concentration of the n-3 PUFA eicosapentaenoic and docosahexaenoic acids (P-PUFA). In a population-based prospective nested case-control study within Northern Sweden seventy-eight cases of a first-ever myocardial infarction were compared with 156 controls with respect to Ery-Hg, P-PUFA and Ery-GSH-Px. Both Ery-Hg and P-PUFA, but not Ery-GSH-Px, were significantly higher in subjects reporting high fish intake (at least one meal per week) than in those with lower intake. This finding suggests that Ery-Hg and P-PUFA reflect previous long-term fish intake. Low risk of myocardial infarction was associated with high Ery-Hg or high P-PUFA. In a multivariate model the risk of myocardial infarction was further reduced in subjects with both high Ery-Hg and high P-PUFA (odds ratio 0.16, 95 % CI 0.04, 0.65). In conclusion, there is a strong inverse association between the risk of a first myocardial infarction and the biomarkers of fish intake, Ery-Hg and P-PUFA, and this association is independent of traditional risk factors.
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| 4. |
- Bergdahl, Ingvar A., et al.
(författare)
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Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes
- 1997
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Ingår i: Basic and Clinical Pharmacology and Toxicology. - : Wiley. - 0901-9928. ; 81:4, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P = 0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.
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| 5. |
- Hermans, C., et al.
(författare)
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Pharmacokinetic modelling and validation of the half-life extension needed to reduce the burden of infusions compared with standard factor VIII
- 2018
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 24:3, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Currently, no universally accepted definition of extended half-life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half-life extension ratio required for a reduction in dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII. Aim: To identify the half-life extension ratio required to decrease rFVIII dosing frequency by at least 1 day while maintaining the proportion of patients with plasma rFVIII levels above 1 IU/dL and without increasing the total weekly dose. Methods: A previously published population pharmacokinetic model for standard rFVIII was used to estimate the percentage of patients with factor VIII (FVIII) levels always >1 IU/dL using various benchmark regimens. Using modelling, dosing frequency was reduced while rFVIII half-life was extended until the percentage of patients with FVIII >1 IU/dL equalled that of the benchmark regimen. Results: Benchmark 3×/wk dosing totalling 100 IU/kg/wk of rFVIII resulted in 56.6% of patients with FVIII levels always >1 IU/dL. With 2×/wk dosing, totalling 80 or 90 IU/kg/wk, half-life extensions required to maintain 56.6% of patients at FVIII levels >1 IU/dL were 1.30 and 1.26, respectively. A half-life extension ratio of 1.33 was required to change dosing from every 48 hours to every 72 hours (both at 105 IU/kg/wk) while maintaining 92.8% of patients with FVIII >1 IU/dL. Conclusion: Based on this investigation, EHL rFVIII products should have a minimum half-life extension ratio of 1.3 to provide a reduction in dosing frequency from 3× to 2×/wk compared with standard rFVIII products while maintaining the same minimum FVIII trough level.
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| 6. |
- Dulloo, A G, et al.
(författare)
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Body composition phenotypes in pathways to obesity and the metabolic syndrome.
- 2010
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 34 Suppl 2, s. S4-17
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic changes in body weight have long been recognized as important indicators of risk for debilitating diseases. While weight loss or impaired growth can lead to muscle wastage, as well as to susceptibility to infections and organ dysfunctions, the development of excess fat predisposes to type 2 diabetes and cardiovascular diseases, with insulin resistance as a central feature of the disease entities of the metabolic syndrome. Although widely used as the phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI), that is, weight/height(2) (H(2)), which was developed as an operational definition for classifying both obesity and malnutrition, has considerable limitations in delineating fat mass (FM) from fat-free mass (FFM), in particular at the individual level. After an examination of these limitations within the constraints of the BMI-FM% relationship, this paper reviews recent advances in concepts about health risks related to body composition phenotypes, which center upon (i) the partitioning of BMI into an FM index (FM/H(2)) and an FFM index (FFM/H(2)), (ii) the partitioning of FFM into organ mass and skeletal muscle mass, (iii) the anatomical partitioning of FM into hazardous fat and protective fat and (iv) the interplay between adipose tissue expandability and ectopic fat deposition within or around organs/tissues that constitute the lean body mass. These concepts about body composition phenotypes and health risks are reviewed in the light of race/ethnic variability in metabolic susceptibility to obesity and the metabolic syndrome.
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| 7. |
- Mutsenko, Vitalii V, et al.
(författare)
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Novel chitin scaffolds derived from marine sponge Ianthella basta for tissue engineering approaches based on human mesenchymal stromal cells : Biocompatibility and cryopreservation.
- 2017
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 104:Pt B, s. 1955-1965
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Tidskriftsartikel (refereegranskat)abstract
- The extraordinary biocompatibility and mechanical properties of chitinous scaffolds from marine sponges endows these structures with unique properties that render them ideal for diverse biomedical applications. In the present work, a technological route to produce "ready-to-use" tissue-engineered products based on poriferan chitin is comprehensively investigated for the first time. Three key stages included isolation of scaffolds from the marine demosponge Ianthella basta, confirmation of their biocompatibility with human mesenchymal stromal cells, and cryopreservation of the tissue-like structures grown within these scaffolds using a slow cooling protocol. Biocompatibility of the macroporous, flat chitin scaffolds has been confirmed by cell attachment, high cell viability and the ability to differentiate into the adipogenic lineage. The viability of cells cryopreserved on chitin scaffolds was reduced by about 30% as compared to cells cryopreserved in suspension. However, the surviving cells were able to retain their differentiation potential; and this is demonstrated for the adipogenic lineage. The results suggest that chitin from the marine demosponge I. basta is a promising, highly biocompatible biomaterial for stem cell-based tissue-engineering applications.
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| 8. |
- Börjesson, Jimmy, et al.
(författare)
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In vivo XRF analysis of mercury: the relation between concentrations in the kidney and the urine
- 1995
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 40:3, s. 413-426
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine the concentrations of mercury in organs of occupationally exposed workers using in vivo x-ray fluorescence analysis. Twenty mercury exposed workers and twelve occupationally unexposed referents participated in the study. Their mercury levels in kidney, liver and thyroid were measured using a technique based on excitation with partly plane polarized photons. The mercury levels in blood and urine were determined using atomic absorption spectrophotometry. The detection limit for mercury in the kidney was exceeded in nine of the exposed workers, but in none of the referents. The mean kidney mercury concentration (including estimates below the detection limits) was 24 mu g g(-1) in the exposed workers, and 1 mu g g(-1) in the referents. The association between mercury in the kidney and in urine was statistically significant, but it was unclear whether the relation was linear. The measurements on liver (n = 10) and thyroid (n = 8) in the exposed workers showed mercury levels below the detection limit. The study shows that it is now possible to measure the mercury concentrations in kidneys of occupationally exposed persons, using in vivo x-ray fluorescence. The estimated concentrations are in reasonable agreement with the limited human autopsy data, and the results of animal studies.
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| 9. |
- Herrstrom, Per, et al.
(författare)
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Dental amalgam, low-dose exposure to mercury, and urinary proteins in young Swedish men
- 1995
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Ingår i: Archives of Environmental Health. - 0003-9896. ; 50:2, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure to inorganic mercury can cause kidney injury. Evidence gained from occupational medicine indicates that individuals who are exposed to only environmental sources, including amalgam tooth fillings, are at very little risk. Animal experiments, however, have revealed glomerular lesions of immunologic origin after low-dose exposure to inorganic mercury. In this study, the association between the number of amalgam tooth surfaces, urinary mercury, and proteinuria was explored in a sample of 48 randomly selected, apparently healthy male students who were 17-22 y of age. Presence of any of the following proteins in two separate urine samples was considered to be potentially indicative of any tubular and/or glomerular lesion: albumin, alpha-1-microglobulin (HC-protein), kappa and lambda light chains, and N-acetyl-beta-D-glucosaminidase. No significant relationship was found between any of the proteins and amalgam or urinary mercury. The results of this study did not suggest that amalgam fillings cause kidney dysfunction in humans.
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| 10. |
- Waterton, John C., et al.
(författare)
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Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems
- 2019
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 59, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many translational MR biomarkers derive from measurements of the water proton longitudinal relaxation rate R 1 , but evidence for between-site reproducibility of R 1 in small-animal MRI is lacking. Objective: To assess R 1 repeatability and multi-site reproducibility in phantoms for preclinical MRI. Methods: R 1 was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1–13 days. R 1 was analysed in three different regions of interest, giving 360 measurements in total. Root-mean-square repeatability and reproducibility coefficients of variation (CoV) were calculated. Propagation of reproducibility errors into 21 translational MR measurements and biomarkers was estimated. Relaxivities were calculated. Dynamic signal stability was also measured. Results: CoV for day-to-day repeatability (N = 180 regions of interest) was 2.34% and for between-centre reproducibility (N = 9 centres) was 1.43%. Mostly, these do not propagate to biologically significant between-centre error, although a few R 1 -based MR biomarkers were found to be quite sensitive even to such small errors in R 1 , notably in myocardial fibrosis, in white matter, and in oxygen-enhanced MRI. The relaxivity of aqueous Ni 2+ in 2% agarose varied between 0.66 s −1 mM −1 at 3 T and 0.94 s −1 mM −1 at 11.7T. Interpretation: While several factors affect the reproducibility of R 1 -based MR biomarkers measured preclinically, between-centre propagation of errors arising from intrinsic equipment irreproducibility should in most cases be small. However, in a few specific cases exceptional efforts might be required to ensure R 1 -reproducibility.
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