| 1. |
- Rollman, Ola, et al.
(författare)
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Platelet derived growth factor (PDGF) responsive epidermis formed from human keratinocytes transduced with the PDGF beta receptor gene.
- 2003
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Ingår i: J Invest Dermatol. ; 120, s. 742-
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor is a major proliferative and migratory stimulus for connective tissue cells during the initiation of skin repair processes. In response to injury, locally produced platelet-derived growth factor is secreted by a diversity of cutaneous cell types whereas target activity is confined to cells of mesenchymal origin, e.g. dermal fibroblasts and smooth muscle cells. Although epidermal cells contribute to cutaneous platelet-derived growth factor activity by their ample capacity to secrete platelet-derived growth factor ligand, normal epidermal keratinocytes are not known to express any member of the platelet-derived growth factor receptor family. In order to study if epidermis may be genetically transformed to a platelet-derived growth factor sensitive compartment we aimed to introduce the gene encoding human platelet-derived growth factor receptor beta (PDGF beta R) into epidermal keratinocytes using a retrovirus-derived vector. Successful gene transfer to primary cells was confirmed by immunofluorescence staining, southern blotting, and ligand-induced receptor autophosphorylation. By culturing a mixture of PDGF beta R-transduced and unmodified keratinocytes at the air-liquid interface on devitalized dermis, we were able to establish a multilayered epithelium showing histologic similarities to that evolved from native keratinocytes or keratinocytes transduced with the reporter gene encoding enhanced green fluorescent protein. Receptor-modified epidermal tissue cultured for 6 days and examined by immunofluorescence microscopy was shown to contain PDGF beta R-expressing keratinocytes distributed in all layers of living epidermis. By continued tissue culture in serum-containing medium, the epidermis became increasingly cornified although receptor-positive cells were still observed within the viable basal compartment. Stimulation of PDGF beta R-transduced epidermis with recombinant platelet-derived growth factor BB had a mitogenic effect as reflected by an increased frequency of Ki-67 positive keratinocytes. The study demonstrates that transgene expression of human PDGF beta R can be achieved in epidermal keratinocytes by retroviral transduction, and that ligand activation of such gene-modified skin equivalent enhances cell proliferation. In perspective, viral PDGF beta R gene transfer to keratinocytes may be a useful approach in studies of receptor tyrosine kinase mediated skin repair and epithelialization.
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| 2. |
- Starch-Jensen, Thomas, et al.
(författare)
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Maxillary Sinus Floor Augmentation With Synthetic Bone Substitutes Compared With Other Grafting Materials : A Systematic Review and Meta-analysis
- 2018
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Ingår i: Implant Dentistry. - : Lippincott Williams & Wilkins. - 1056-6163 .- 1538-2982. ; 27:3, s. 363-374
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Forskningsöversikt (refereegranskat)abstract
- Objective: To test the hypotheses of no differences in implant treatment outcome after maxillary sinus floor augmentation (MSFA) with synthetic bone substitutes (SBS) compared with other grafting materials applying the lateral window technique. Materials and Methods: A MEDLINE/PubMed, Embase and Cochrane Library search in combination with hand-search of selected journals was conducted. Results: Five randomized controlled trials with low risk of bias fulfilled the inclusion criteria. SBS disclosed high survival rate of suprastructures and implants with no significant differences compared to autogenous bone graft or xenograft. Meta-analysis revealed a patient-based implant survival rate of 0.98 (confidence interval: 0.89-1.08), indicating no differences between SBS and xenograft. SBS demonstrated significant less newly formed bone compared with autogenous bone graft, whereas no significant difference was revealed as compared to xenograft. High implant stability values, limited periimplant marginal bone loss, and few complications were reported with SBS. Conclusions: There seem to be no differences in implant treatment outcome after MSFA with SBS compared to other grafting materials.
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| 3. |
- Voight, Benjamin F, et al.
(författare)
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Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
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| 4. |
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| 5. |
- Alhede, Christina, et al.
(författare)
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Antiarrhythmic medication is superior to catheter ablation in suppressing supraventricular ectopic complexes in patients with atrial fibrillation
- 2017
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 244, s. 186-191
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Tidskriftsartikel (refereegranskat)abstract
- Background: Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24 months of follow-up. Methods: Patients with paroxysmal AF (N = 260) enrolled in the MANTRA PAF trial were treated with AAD (N = 132) or CA (N = 128). At baseline and 3, 6, 12, 18 and 24 months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. Results: Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p = 0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3 months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24 months of follow-up. Conclusion: AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA. (C) 2017 Elsevier B.V. All rights reserved.
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| 6. |
- Alhede, Christina, et al.
(författare)
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Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation
- 2018
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Ingår i: Europace. - : OXFORD UNIV PRESS. - 1099-5129 .- 1532-2092. ; 20:1, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- Aims Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and amp;gt;= 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF amp;gt;= 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (amp;gt;= 783 SVEC: HR 4.6 [1.9-11.5], P amp;lt; 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence amp;lt; 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC amp;gt;= 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.
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| 7. |
- Alhede, Christina, et al.
(författare)
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The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation
- 2018
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 250, s. 122-127
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients +/- 57 years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). Methods: In total, 260 patients with LVEF amp;gt;40% and age amp;lt;= 70 years were randomized to AAD (N = 132) or CA (N = 128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24 months and were categorized according to median age +/- 57 years. We used multi-variate Cox regression analyses and we defined high SVEC burden at 3 months of follow-up as the upper 75th percentile amp;gt;195 SVEC/day. AF recurrence was defined as AF amp;gt;= 1 min, AF-related cardioversion or hospitalization. Results: Age amp;gt;57 years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p = 0.02). After CA, we observed a higher SVEC burden during follow-up in patients amp;gt;57 years which was not observed in the younger age group treatedwith CA (p = 0.006). High SVEC burden at 3 months after CA was associated with AF recurrence in older patients but not in younger patients (amp;gt;57 years: HR 3.4 [1.4-7.9], p = 0.005). We did not find any age-related differences after AAD. Conclusion: We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients. (C) 2017 Elsevier B.V. All rights reserved.
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| 8. |
- Aludden, Hanna, et al.
(författare)
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Histological and histomorphometrical outcome after lateral guided bone regeneration augmentation of the mandible with different ratios of deproteinized bovine bone mineral and autogenous bone. A preclinical in vivo study
- 2020
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 31:10, s. 1025-1036
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: To test the hypotheses of no differences in (I) percentage of bone (POB), non-mineralized tissue (NMT), and deproteinized bovine bone mineral (DBBM), and (II) ingrowth of mineralized bone after lateral guided bone regeneration (GBR) augmentation of the mandible with different ratios of DBBM and particulate autogenous bone (PAB) at different time points. Material and methods: Twenty-four minipigs were randomly allocated into three groups. Lateral augmentation in 96 sites (4 in each animal) was performed unilaterally with a standardized quantity of grafting material in each animal with different ratios of DBBM and PAB (50:50, 75:25, 100:0) and autogenous bone block in combination with DBBM and covered with a collagen membrane. The percentage of different tissues in the graft and ingrowth of mineralized bone was assessed by histomorphometrical and histological analyses after 10, 20, and 30 weeks, respectively. Results: The POB was 54% (50:50), 50% (75:25), and 48% (100:0) after 10 weeks, 60% (50:50), 61% (75:25), and 60% (100:0) after 20 weeks, and 63% (50:50), 62% (75:25), and 62% (100:0) after 30 weeks. There was no significant difference between the groups at any time points. There was a significant increase in POB and a significant decrease in NMT for 75:25 and 100:0 from 10 to 30 weeks. All ratios demonstrated a non-complete ingrowth of mineralized bone into the graft after 10 weeks and complete mineralization after 30 weeks. Conclusion: Within the limitations of the present study, it seems like addition of autogenous bone to DBBM for LRA did not affect the bone formation nor graft incorporation after 10–30 weeks of healing. However, a prolonged healing time seems to result in an increased POB for all ratios.
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| 9. |
- Aludden, Hanna, 1984, et al.
(författare)
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Histological and radiological outcome after horizontal guided bone regeneration with bovine bone mineral alone or in combination with bone in edentulous atrophic maxilla: A randomized controlled trial
- 2024
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Ingår i: CLINICAL ORAL IMPLANTS RESEARCH. - 0905-7161 .- 1600-0501.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo assess the radiological and histological outcome after horizontal guided bone regeneration (GBR) with deproteinized bovine bone mineral (DBBM) alone or in combination with particulate autogenous bone (PAB).Materials and MethodsEighteen edentulous patients with an alveolar ridge of <= 4 mm were included in this split-mouth randomized controlled trial. Horizontal GBR with a graft composition of 100% DBBM (100:0) on one side and 90% DBBM and 10% PAB (90:10) on the other side were conducted in all patients. Cone beam computed tomography (CBCT) was obtained preoperatively, immediately postoperative, and after 10 months of healing. Width and volumetric changes in the alveolar process were measured on CBCT. Implants were placed after 10 months of graft healing where biopsies were obtained for histomorphometrical evaluation.ResultsThe gained widths were 4.9 (+/- 2.4) mm (100:0) and 4.5 (+/- 2.0) mm (90:10) at 3 mm from the top of the crest, and 5.6 (+/- 1.3) mm (100:0) and 4.6 (+/- 2.1) mm (90:10) at 6 mm from the top of the crest. The mean volumetric reductions were 32.8% (+/- 23.8) (100:0) and 38.2% (+/- 23.2) (90:10). Histomorphometry revealed that mean percentages of bone were 50.8% (+/- 10.7) (100:0) and 46.4% (+/- 11.3) (90:10), DBBM were 31.6% (+/- 12.6) (100:0) and 35.4% (+/- 14.8) (90:10), and non-mineralized tissue were 17.6% (+/- 11.7; 100:0) and 18.2% (+/- 18.2) (90:10). No significant differences were evident between in any evaluated parameters.ConclusionsThere were no additional effects of adding PAB to DBBM regarding bone formation, width changes, or volumetric changes after 10 months of graft healing.
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| 10. |
- Aludden, H., et al.
(författare)
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Histomorphometric analyses of area fraction of different ratios of Bio-Oss((R)) and bone prior to grafting procedures - An in vitro study to demonstrate a baseline
- 2018
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 29:2, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe objective of this study was to estimate the area fraction of different ratios of Bio-Oss((R)) and bone, prior to grafting in an in vitro model to demonstrate a histomorphometric baseline. MethodsBio-Oss((R)) particles were mixed with autogenous bone from pig jaw in three different ratios (50:50, 80:20 and 100:0) and packed in rice paper in a standardized procedure. Histomorphometric analyses were performed in 25 specimens and 74 regions of interest. The area percentage of Bio-Oss((R)), bone, and non-mineralized tissue (NMT) were calculated. Results were reported as mean values and 95% confidence interval (CI). ResultsThe mean area fraction of Bio-Oss((R)) was 20.6% (CI: 18.2-23) in the 50:50 mixture, 33.6% (CI: 29.7-37.6) in the 80:20 mixture, and 43.4% (CI: 40.5-46.3) in the 100:0 mixture. The mean area fraction of NMT was 60.5% (CI: 57.9-63.1) in the 50:50 mixture, 59.6% (CI: 56.4-62.7) in the 80:20 mixture, and 56.6% (CI: 53.7-59.5) in the 100:0 mixture. The mean area fraction of bone was 18.9% (CI: 16.9-20.9) in the 50:50 mixture and 6.8% (CI: 5-8.6) in the 80:20 mixture. ConclusionThere is a great difference in the clinically estimated percentage and the histomorphometrically evaluated percentage of Bio-Oss((R)) at baseline, prior to grafting. The area fraction of different tissues presented in this study may be beneficial as guidance for histomorphometrical baseline calculations when different mixtures of Bio-Oss((R)) and autogenous bone are used as grafting materials.
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