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| 4. |
- Barosi, G, et al.
(författare)
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Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms : consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
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| 8. |
- Hellstrom-Lindberg, E., et al.
(författare)
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A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor : Significant effects on quality of life
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 120, s. 1037-
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Tidskriftsartikel (refereegranskat)abstract
- We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo = 500 U/l and a transfusion need of < 2 units/month predicted a high probability of response to treatment, S-Epo > 500 U/l and =2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.
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| 9. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 12. |
- Ambrosio, L., et al.
(författare)
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Massive foreign body reaction and osteolysis following primary anterior cruciate ligament reconstruction with the ligament augmentation and reconstruction system (LARS): a case report with histopathological and physicochemical analysis
- 2022
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Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous hamstrings and patellar tendon have historically been considered the gold standard grafts for anterior cruciate ligament reconstruction (ACLR). In the last decades, the utilization of synthetic grafts has re-emerged due to advantageous lack of donor site morbidity and more rapid return to sport. The Ligament Augmentation and Reconstruction System (LARS) has demonstrated to be a valid and safe option for ACLR in the short term. However, recent studies have pointed out the notable frequency of associated complications, including synovitis, mechanical failure, and even chondrolysis requiring joint replacement. Case presentation: We report the case of a 23-year-old male who developed a serious foreign body reaction with wide osteolysis of both femoral and tibial tunnels following ACLR with LARS. During first-stage arthroscopy, we performed a debridement of the pseudocystic mass incorporating the anterior cruciate ligament (ACL) and extending towards the tunnels, which were filled with autologous anterior iliac crest bone graft chips. Histological analysis revealed the presence of chronic inflammation, fibrosis, and foreign body giant cells with synthetic fiber inclusions. Furthermore, physicochemical analysis showed signs of fiber depolymerization, increased crystallinity and formation of lipid peroxidation-derived aldehydes, which indicate mechanical aging and instability of the graft. After 8 months, revision surgery was performed and ACL revision surgery with autologous hamstrings was successfully carried out. Conclusions: The use of the LARS grafts for ACLR should be cautiously contemplated considering the high risk of complications and early failure.
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| 13. |
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| 14. |
- Brown, Jeffrey N, et al.
(författare)
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AQUEOUSANDLIPID NUCLEAR MAGNETIC RESONANCE METABOLOMIC PROFILES OF THE EARTHWORM APORRECTODEA CALIGINOSA SHOW POTENTIAL AS AN INDICATOR SPECIES FOR ENVIRONMENTAL METABOLOMICS
- 2014
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268. ; 33:10, s. 2313-2322
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Tidskriftsartikel (refereegranskat)abstract
- The common pasture earthworm Aporrectodea caliginosa has often been neglected in environmental metabolomics in favor of species easily bred in the laboratory. The present study assigns aqueous metabolites in A. caliginosa using high-resolution 1- and 2-dimensional nuclear magnetic resonance (NMR) spectroscopy. In total, 51 aqueous metabolites were identified, including typical amino acids (alanine, leucine, asparagine, phenylalanine), sugars (maltose, glucose), the dominant earthworm-specific 2-hexyl-5-ethyl-furansulfonate, and several previously unreported metabolites (oxoglutarate, putrescine). Examining the lesser-known earthworm lipid metabolome showed various lipid fatty acyl chains, cholesterol, and phosphatidylcholine. To briefly test if the NMR metabolomic techniques could differentiate A. caliginosa from different sites, earthworms were collected from 2 adjacent farms. Orthogonal partial least squares discriminant analysis detected metabolomic differences, suggesting the worms from the 2 sites differed in their energy metabolism, as indicated by altered levels of alanine, glutamine, glutamate, malate, fumarate, and lipids. Evidence of greater utilization of lipid energy reserves and onset of protein catabolism was also present. While the precise cause of the metabolomic differences could not be determined, the results show the potential of this species for further environmental metabolomic studies. Environ Toxicol Chem 2014;33:2313-2322. (c) 2014 SETAC
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| 15. |
- Caparrós, T., et al.
(författare)
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The relationship of practice exposure and injury rate on game performance and season success in professional male basketball
- 2016
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Ingår i: Journal of Sports Science and Medicine. - 1303-2968. ; 15:3, s. 397-402
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of this study were to determine the relationship among game performance, injury rate, and practice exposure in a professional male basketball team. A retroospective analysis of prospective collected data was conducted over seven consecutive seasons (2007/2008 to 2013/2014). Data collection included sports performance during competition (statistical evaluation), injury rate, and total exposure (games and practices). Over the surveillance period, 162 injuries (91 practice; 71 matches) occurred over 32,668 hours of exposure (556 games and 2005 practices). There was a strong positive correlation between: 1) exposure (total number of practices and hours of exposure) and the total number of injuries (r = 0.77; p = 0.04); 2) exposure (total hours of exposure and total hours of practice exposure) and performance (total team ranking) (r = 0.77 and p = 0.04, and r = 0.8 and p = 0.03, respectively); and 3) total number of injuries and performance (total team ranking) (r = 0.84; p = 0.02). While increasing practice and competition time is related to greater team performance, it also increases the number of injuries. However, higher injury rates were not associated with worse overall team performance. Efforts to reduce high-risk activity during practice, optimally replaced with injury prevention training, might help to reduce injury risk. © Journal of Sports Science and Medicine.
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| 16. |
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| 17. |
- De Gouw, J. A., et al.
(författare)
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Airborne Measurements of Ethene from Industrial Sources Using Laser Photo-Acoustic Spectroscopy
- 2009
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:7, s. 2437-2442
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Tidskriftsartikel (refereegranskat)abstract
- A laser photoacoustic spectroscopy (LPAS) instrument was developed and used for aircraft measurements of ethene from industrial sources near Houston, Texas. The instrument provided 20 s measurements with a detection limit of less than 0.7 ppbv. Data from this instrument and from the GC-FID analysis of air samples collected in flight agreed within 15% on average. Ethene fluxes from the Mt. Belvieu chemical complex to the northeast of Houston were quantified during 10 different flights. The average flux was 520 +/- 140 kg h(-1) in agreement with independent results from solar occultation flux (SOF) measurements, and roughly an order of magnitude higher than regulatory emission inventories indicate. This study shows that ethene emissions are routinely at levels that qualify as emission upsets, which need to be reported to regional air quality managers.
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| 24. |
- Gunnarsson, Jonas S., et al.
(författare)
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Response of marine benthic fauna to thin-layer capping with activated carbon in a large-scale field experiment in the Grenland fjords, Norway
- 2017
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 24:16, s. 14218-14233
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Tidskriftsartikel (refereegranskat)abstract
- A field experiment with thin-layer capping was conducted in the Grenland fjords, Norway, for remediation in situ of mercury and dioxin-contaminated sediments. Experimental fields at 30 and 95 m depth were capped with (i) powdered activated carbon (AC) mixed with clay (AC+clay), (ii) clay, and (iii) crushed limestone. Ecological effects on the benthic community and species-feeding guilds were studied 1 and 14 months after capping, and a total of 158 species were included in the analyses. The results show that clay and limestone had only minor effects on the benthic community, while AC+clay caused severe perturbations. AC+clay reduced the abundance, biomass, and number of species by up to 90% at both 30 and 95 m depth, and few indications of recovery were found during the period of this investigation. The negative effects of AC+clay were observed on a wide range of species with different feeding strategies, although the suspension feeding brittle star Amphiura filiformis was particularly affected. Even though activated carbon is effective in reducing sediment-to-water fluxes of dioxins and other organic pollutants, this study shows that capping with powdered AC can lead to substantial disturbances to the benthic community.
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| 29. |
- Jonsdottir, Berglind, et al.
(författare)
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Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents
- 2013
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Ingår i: Diabetologia. - : Springer Verlag (Germany). - 0012-186X .- 1432-0428. ; 56:8, s. 1735-1742
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.
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| 30. |
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| 31. |
- Leckner, Bo G, 1936, et al.
(författare)
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Influence of attrition on combustion of biomass pellet char
- 2000
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Ingår i: International Energy Agency Workshop, Attrition Phenomena Fluidized Bed Conversion , Oct 30, University of Salerno, Italy/ Salatino P..
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 32. |
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| 33. |
- Palchonok, G.I., et al.
(författare)
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Combustion mechanisms of biomass pellet char
- 2001
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Ingår i: First Biennal Meeting of the Scandinavian-Nordic Section of the Combustion Inst, April 18-20, Göteborg, 2001. ; , s. 49-54
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Schultz, J. K., et al.
(författare)
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European Society of Coloproctology: guidelines for the management of diverticular disease of the colon
- 2020
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 22:52, s. 5-28
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Tidskriftsartikel (refereegranskat)abstract
- Aim The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. Methods The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. Results This guideline contains 38 evidence based consensus statements on the management of diverticular disease. Conclusion This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.
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| 39. |
- Simmen, K. A., et al.
(författare)
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Macrocylic inhibitors of hepatitis C virus
- 2012
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Patent (populärvet., debatt m.m.)abstract
- Inhibitors of HCV replication of formula (I)and the N-oxides, salts, and stereoisomers, whereineach dashed line represents an optional double bond;X is N, CH and where X bears a double bond it is C;R1 is —OR7, —NH—SO2R8;R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl;R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl;R4 is aryl or Het; n is 3, 4, 5, or 6;R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het;R6 is C1-6alkoxy, or dimethylamino;R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;aryl is phenyl optionally substituted with one, two or three substituents;Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents;pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
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| 40. |
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| 41. |
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| 43. |
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| 44. |
- Svanborg, Catharina, et al.
(författare)
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The 'innate' host response protects and damages the infected urinary tract
- 2001
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Ingår i: Annals of Medicine. - 1365-2060. ; 33:9, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.
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| 45. |
- Uhler, Jay (Jennifer), et al.
(författare)
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The UbL protein UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes
- 2014
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 443:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- UBTD1 is a previously uncharacterized ubiquitin-like (UbL) domain containing protein with high homology to the mitochondrial Dc-UbP/UBTD2 protein. Here we show that UBTD1 and UBTD2 belong to a family of proteins that is conserved through evolution and found in metazoa, funghi, and plants. To gain further insight into the function of UBTD1, we screened for interacting proteins. In a yeast-2-hybrid (Y2H) screen, we identified several proteins involved in the ubiquitylation pathway, including the UBE2D family of E2 ubiquitin conjugating enzymes. An affinity capture screen for UBTD1 interacting proteins in whole cell extracts also identified members of the UBE2D family. Biochemical characterization of recombinant UBTD1 and UBE2D demonstrated that the two proteins form a stable, stoichiometric complex that can be purified to near homogeneity. We discuss the implications of these findings in light of the ubiquitin proteasome system (UPS). (C) 2013 Published by Elsevier Inc.
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| 46. |
- Öquist, G., et al.
(författare)
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Chlorophyll a fluorescence an alternative method for estimating primary production
- 1982
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Ingår i: Marine Biology. - 1230-7688. ; 68:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- The in vivo chlorophyll a fluorescence index (F+DcM u-F-DcMu/F+DcMU) of natural waters was compared to the 14C-determined primary production, and the fluorescence intensity in the presence of 3-(3,4-dichlorophenyl)-l,l-dimethylurea (F + DCM~) was studied as a function of extracted and spectrophotometrically determined chlorophyll concentrations. Samples were taken every second week from May through October, 1979, at the station "Systrarna" situated in a coastal area of the Bottnian Sea. In addition, samples from the Archipelago Sea of the Baltic were collected on board the Finnish research vessel R/S "Aranda" during the September cruise 1979. The correlations between the fluorescence index and the 14C-determined primary production and between F+DcMu and total chlorophyll concentration were good when samples taken over short time intervals were compared. The shortcomings of both the fluorescence and the 14C methods are discussed. It is concluded that the fluorescence method is useful if it is desirable to follow with high time resolution any changes in the potential for photosynthesis (or pirmary production) in a water mass over relatively short time periods; e.g. during an algal bloom. The fluorescence method can furthermore be technically developed for automatic monitoring with a high time resolution. Efforts are being made in our laboratory to develop the method further to give information about the in situ rates of photosynthesis rather than the potential for photosynthesis in a phytoplankton population.
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| 47. |
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| 48. |
- Alentorn-Geli, E., et al.
(författare)
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The presence of patellar tendinopathy in the bone-patellar tendon-bone autograft may increase the risk of anterior cruciate ligament graft failure
- 2019
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:3, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study was to evaluate the influence of patellar tendinopathy on primary anterior cruciate ligament (ACL) reconstruction graft failure when using bone-patellar tendon-bone (BPTB) autograft.MethodsAll patients undergoing primary ACL reconstruction using ipsilateral BPTB with preoperative magnetic resonance imaging (MRI) available for review were approached for eligibility. The medical charts of included patients were reviewed to obtain demographic information, anatomical characteristics, injury characteristics, treatment characteristics, length of follow-up, and presence of graft failure. A single, fellowship-trained, knee-specialist and blinded researcher performed preoperative MRI interpretation of patellar tendinopathy. The presence/absence of patellar tendinopathy (none, mild, moderate, or severe changes) was compared between patients with (cases) and without (controls) failure of ACL reconstruction. There were 559 cases with a median (range) clinical follow-up was 8 (4-30) months and an average age of 21.5years (82% males).ResultsOf the 559 cases, there were 182 (32.6%) with and 377 (67.4%) without patellar tendinopathy. A total of 32 (5.7%) graft failures occurred. There were a significantly higher failure rate in patients with compared to without patellar tendinopathy (p<0.001), and in patients with compared to without partial tendon tear (p<0.001). The odds ratio (95% confidence interval) for graft failure was 5.9 (2.7-13.1), 20.8 (6.8-63.9) and 54.4 (5.5-539.4) in patients with patellar tendinopathy (compared to absence of patellar tendinopathy), moderate or severe patellar tendinopathy (compared to none or mild patellar tendinopathy), or partial tendon tear (compared to absence of tendon tear), respectively.ConclusionThe presence of patellar tendinopathy increases the risk of BPTB graft failure when used for ACL reconstruction. The use of BPTB autograft is not recommended if patellar tendinopathy is obvious or there are suspicious of partial tendon tear on MRI. In such cases, the surgeon should consider using a different graft.Level of evidenceRetrospective cohort analysis, Level III.
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| 49. |
- Alheim, Katarina, et al.
(författare)
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Identification of a functional glucocorticoid response element in the promoter of the cylcin-dependant kinase inhibitor p57(Kip2)
- 2003
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Ingår i: Journal of Molecular Endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 30:3, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are known regulators of the cell cycle, normally exerting an anti-proliferative effect. We have previously shown that glucocorticoids stimulate expression of p57(Kip2), a member of the Cip/Kip family of cyclin-dependent kinase inhibitors which, in some cell types, may account for the anti-proliferative responses seen after glucocorticoid treatment. The induction of p57(Kip2) involves primary transcriptional effects where no de novo protein synthesis is necessary, suggesting a direct interaction of the glucocorticoid receptor with the p57(Kip2) gene. In this study we have identified a functional glucocorticoid response element (GRE), located 5 kilo bases (kb) upstream of the transcription start site in the human P57(Kip2) promoter. This GRE was functional also when isolated, suggesting a direct transcriptional effect of the glucocorticoid receptor. Furthermore, mutation of this GRE abolished glucocorticoid induction of the reporter gene, whereas mutation of a nearby Sp1 site did not. Using electrophoretic mobility shift assays, we have shown that the -5 kb p57(Kip2) promoter GRE was able to compete with a well-known GRE for glucocorticoid receptor binding. Sequence comparisons with the mouse genome showed that this GRE is highly conserved, further strengthening the biological importance of this site. All these data emphasize the involvement of this GRE in the glucocorticoid-mediated induction of p57(Kip2) expression.
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