| 51. |
- Bramsved, Rebecka, 1982, et al.
(författare)
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Birth Weight, Childhood and Young Adult Overweight, and the Risk of Coronary Heart Disease in Men.
- 2024
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 44:1, s. 314 - 321
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Tidskriftsartikel (refereegranskat)abstract
- Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied.We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively).During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg.We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.
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| 52. |
- Brembeck, Petra, 1977, et al.
(författare)
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Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpartum.
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:2, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Context: Lactation is associated with decreased areal bone mineral density (aBMD). Replenishment occurs especially after ceased lactation. Changes in volumetric BMD (vBMD), microstructure and dimensional parameters are unknown and may clarify the role of lactation for skeletal health. Objective: and main outcomes: To test the hypothesis that lactation is associated with changes in aBMD, vBMD, microstructure and dimensional parameters. Design: At baseline (0.5 months after delivery) and 4, 12 and 18 months thereafter bone was assessed using dual energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Participants: and setting: Eighty-one fair-skinned postpartum women and 21 controls aged 25-40 years were recruited. Completion ratio was 73%. Postpartum women were categorized depending on duration of lactation; 0-3.9, 4-8.9 and ≥9 months. Results: During the first 4 months, aBMD decreased at several sites (geometric mean±SE; -0.73±0.21% to -3.98±0.76%) in women lactating at least 4 months. During the same time, cortical vBMD at ultra-distal tibia decreased in women lactating 4-8.9 months (-0.26±0.08%) and ≥9 months (-0.49±0.10%). At 12 months postpartum, also cortical thickness (≥9 months, -2.48±0.41%) and trabecular thickness (4-8.9 months, -2.14±0.92%; ≥9 months, -2.56±1.21%) were lower than baseline. No decreases were found in women lactating less than 4 months or in controls in these parameters. At 18 months postpartum, both cortical vBMD (≥9 months, -0.77±0.17%) and trabecular thickness (4-8.9 months, -2.25±1.25%; ≥9 months, -3.21±1.41%) were lower in women with long lactation. Conclusions: Decreases in cortical vBMD, thickness, and trabecular thickness at ultra-distal tibia were found in women lactating 4 months or longer. Longer follow-up is needed to confirm whether women with extended lactation recover fully, or whether the changes could potentially lead to increased risk of fracture in later life.
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| 53. |
- Brembeck, Petra, 1977, et al.
(författare)
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Determinants of microstructural, dimensional and bone mineral changes postpartum in Swedish women.
- 2016
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Ingår i: The British journal of nutrition. - 1475-2662. ; 116:10, s. 1736-44
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Tidskriftsartikel (refereegranskat)abstract
- During lactation, areal (a) and volumetric (v) bone mineral density (BMD) are known to temporarily decrease. Factors that affect skeletal changes postpartum are not fully elucidated. The aim was to study determinants of the previously observed changes in aBMD at lumbar spine, and cortical vBMD, microstructure and dimensions at ultra-distal tibia postpartum. Women (25-40 years) were studied longitudinally at 2 weeks (baseline) and 4 months (n 81), 12 months (n 79) and 18 months (n 58) postpartum. At each visit, blood samples were collected, body weight and height were measured and information about lactation habits, oestrogen contraceptives and physical activity was obtained. Ca intake was measured using 4-d food diaries at 4 months postpartum. Serum 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography-tandem MS. Skeletal changes were assessed with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Mean baseline BMI was 24·8 (sd 3·1) kg/m2. Median (quartiles 1-3) duration of total lactation was 8·1 (6·8-10·4) months. Longer duration of full lactation was associated with larger decreases of lumbar spine aBMD and tibia vBMD and microstructure. Higher baseline body weight was associated with smaller decreases in tibia vBMD and microstructure. Higher Ca intake was associated with smaller decreases in tibia cortical vBMD and thickness. Higher baseline 25OHD was only associated with larger decreases in lumbar spine aBMD. In conclusion, lactation and body weight were the main determinants of skeletal changes during the first 18 months postpartum. Ca intake and serum concentrations of 25OHD appear to have different associations with cortical and trabecular bone.
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| 54. |
- Brittberg, Mats, 1953, et al.
(författare)
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Autolog broskcellstransplantation. Smärtlindring och återställd ledfunktion är målet : Autologous cartilage cell transplantation. The goal is pain relief and restored joint function
- 1995
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Ingår i: Nordisk medicin. - 0029-1420. ; 110:12, s. 330-4
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Tidskriftsartikel (refereegranskat)abstract
- Chondral and osteochondral damage is a common result of trauma to the joints. The capacity of cartilage to heal such damage is poor, and repetitive wear on joint surfaces that do not heal results in impaired joint function, which can culminate in full blown arthrosis. Thus, it is important to improve our knowledge of cartilage regenerative potential, and develop methods to forestall progression to arthrosis by promoting the early healing of cartilage damage. Autologous cartilage cell transplantation may be a mean of healing cartilage damage. A method of cultivating autologous chondrocytes for transplantation in the treatment of isolated damage to articular cartilage of the knee is presented in the article.
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| 55. |
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| 56. |
- Brittberg, Mats, 1953, et al.
(författare)
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Cellular aspects on treatment of cartilage injuries.
- 1993
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Ingår i: Agents and actions. Supplements. - 0379-0363. ; 39, s. 237-41
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Tidskriftsartikel (refereegranskat)abstract
- Cellular aspects on articular cartilage growth and development are discussed. Cells with chondrogenic potential are described and current treatment models for cartilage injuries are considered. A rabbit model for treatment of articular cartilage defects with autologous cultured and transplanted chondrocytes for treatment of knee cartilage defects in humans are discussed.
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| 57. |
- Brittberg, Mats, 1953, et al.
(författare)
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Rabbit articular cartilage defects treated with autologous cultured chondrocytes.
- 1996
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Ingår i: Clinical orthopaedics and related research. - 0009-921X. ; :326, s. 270-83
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Tidskriftsartikel (refereegranskat)abstract
- Adult New Zealand rabbits were used to transplant autologously harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously and were 3 mm in diameter, extending down to the calcified zone. Healing of the defects was assessed by gross examination, light microscope, and histological-histochemical scoring at 8, 12, and 52 weeks. Chondrocyte transplantation significantly increased the amount of newly formed repair tissue compared to the found in control knees in which the lesion was solely covered by a periosteal flap. In another experiment, carbon fiber pads seeded with chondrocytes were used as scaffolds, and repair significantly increased at both 12 and 52 weeks compared to knees in which scaffolds without chondrocytes were implanted. The histologic quality scores of the repair tissue were significantly better in all knees in which defects were treated with chondrocytes compared to knees treated with periosteum alone and better at 52 weeks compared to knees in which defects were treated with carbon scaffolds seeded with chondrocytes. The repair tissue, however, tended to incomplete the bonding to adjacent cartilage. This study shows that isolated autologous articular chondrocytes that have been expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesions. A gradual maturation of the hyalinelike repair with a more pronounced columnarization was noted as late as 1 year after surgery.
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| 58. |
- Brittberg, Mats, 1953, et al.
(författare)
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Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.
- 1994
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Ingår i: The New England journal of medicine. - 0028-4793. ; 331:14, s. 889-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. METHODS. The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. RESULTS. Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and swelling in all patients. After three months, arthroscopy showed that the transplants were level with the surrounding tissue and spongy when probed, with visible borders. A second arthroscopic examination showed that in many instances the transplants had the same macroscopic appearance as they had earlier but were firmer when probed and similar in appearance to the surrounding cartilage. Two years after transplantation, 14 of the 16 patients with femoral condylar transplants had good-to-excellent results. Two patients required a second operation because of severe central wear in the transplants, with locking and pain. A mean of 36 months after transplantation, the results were excellent or good in two of the seven patients with patellar transplants, fair in three, and poor in two; two patients required a second operation because of severe chondromalacia. Biopsies showed that 11 of the 15 femoral transplants and 1 of the 7 patellar transplants had the appearance of hyaline cartilage. CONCLUSION. Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
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| 59. |
- Brommage, Robert, et al.
(författare)
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High Fidelity of Mouse Models Mimicking Human Genetic Skeletal Disorders
- 2020
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The 2019 International Skeletal Dysplasia Society nosology update lists 441 genes for which mutations result in rare human skeletal disorders. These genes code for enzymes (33%), scaffolding proteins (18%), signal transduction proteins (16%), transcription factors (14%), cilia proteins (8%), extracellular matrix proteins (5%), and membrane transporters (4%). Skeletal disorders include aggrecanopathies, channelopathies, ciliopathies, cohesinopathies, laminopathies, linkeropathies, lysosomal storage diseases, protein-folding and RNA splicing defects, and ribosomopathies. With the goal of evaluating the ability of mouse models to mimic these human genetic skeletal disorders, a PubMed literature search identified 260 genes for which mutant mice were examined for skeletal phenotypes. These mouse models included spontaneous and ENU-induced mutants, global and conditional gene knockouts, and transgenic mice with gene over-expression or specific base-pair substitutions. The human X-linked gene ARSE and small nuclear RNA U4ATAC, a component of the minor spliceosome, do not have mouse homologs. Mouse skeletal phenotypes mimicking human skeletal disorders were observed in 249 of the 260 genes (96%) for which comparisons are possible. A supplemental table in spreadsheet format provides PubMed weblinks to representative publications of mutant mouse skeletal phenotypes. Mutations in 11 mouse genes (Ccn6, Cyp2r1, Flna, Galns, Gna13, Lemd3, Manba, Mnx1, Nsd1, Plod1, Smarcal1) do not result in similar skeletal phenotypes observed with mutations of the homologous human genes. These discrepancies can result from failure of mouse models to mimic the exact human gene mutations. There are no obvious commonalities among these 11 genes. Body BMD and/or radiologic dysmorphology phenotypes were successfully identified for 28 genes by the International Mouse Phenotyping Consortium (IMPC). Forward genetics using ENU mouse mutagenesis successfully identified 37 nosology gene phenotypes. Since many human genetic disorders involve hypomorphic, gain-of-function, dominant-negative and intronic mutations, future studies will undoubtedly utilize CRISPR/Cas9 technology to examine transgenic mice having genes modified to exactly mimic variant human sequences. Mutant mice will increasingly be employed for drug development studies designed to treat human genetic skeletal disorders.
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| 60. |
- Brommage, Robert, et al.
(författare)
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NOTUM inhibition increases endocortical bone formation and bone strength
- 2019
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Ingår i: Bone Research. - : Springer Science and Business Media LLC. - 2095-4700 .- 2095-6231. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum(-/-) mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.
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