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- Björksved, Margitha, 1964-, et al.
(författare)
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Closed vs open surgical exposure of palatally displaced canines : surgery time, postoperative complications, and patients' perceptions
- 2018
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Ingår i: European Journal of Orthodontics. - : Oxford University Press. - 0141-5387 .- 1460-2210. ; 40:6, s. 626-635
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Tidskriftsartikel (refereegranskat)abstract
- Background: Closed and open surgical techniques are two different main approaches to surgical exposure of palatally displaced canines (PDCs). Because there is insufficient evidence to support one technique over the other, there is a need for randomized controlled trials.Objectives: To compare surgery time, complications and patients' perceptions between closed and open surgical techniques in PDCs.Trial design: The trial was a multicentre, randomized, controlled trial with two parallel groups randomly allocated in a 1:1 ratio.Material and methods: Study participants were 119 consecutive patients from 3 orthodontic centres, with PDCs planned for surgical exposure, randomly allocated according to a computer-generated randomization list, using concealed allocation. Full-thickness mucoperiosteal flap was raised, and bone covering the canine was removed in both interventions. In closed exposure, an attachment with a chain was bonded to the canine and the flap was sutured back with the chain penetrating the mucosa. In open exposure, a window of tissue around the tooth was removed and glass ionomer cement placed on the canine crown, to prevent gingival overgrowth during spontaneous eruption. Patient perceptions were assessed with two questionnaires, for the evening on the day of operation and 7 days post-surgery.Blinding: It was not possible to blind either patients or care providers to the interventions. The outcome assessors were blinded and were unaware of patients' intervention group.Results: Seventy-five girls and 44 boys, mean age 13.4 years (SD 1.46) participated in the study and got either of the interventions (closed exposure, n = 60; open exposure, n = 59). Surgery time did not differ significantly between the interventions. Complications though were more severe in bilateral cases and the patients experienced more pain and impairment in the open group.Conclusion: There were no statistically significant differences regarding surgery time between the groups. Postoperative complications were similar between the groups in unilateral PDCs, but more common in the open group in bilateral cases. More patients in the open group experienced pain and impairment compared to the closed group.Trial registration: Trial registration: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201.
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- Björksved, Margitha, 1964-
(författare)
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Open vs closed exposure of palatally displaced canines : clinical, patient-related outcomes and health economics
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The maxillary permanent canine usually erupts in the mouth between the ages of 11 and 12 years. Sometimes the canines are displaced toward the palatal side of the dental arch and eruption is disturbed. Palatally displaced canines (PDCs) are a frequent dental anomaly, present in 2% of the young population. If untreated, there is risk of damage to the roots of the adjacent teeth and potential tooth loss. Thus, early interceptive treatment with extraction of the deciduous canine should be undertaken, with the aim to improve the PDC eruption path. If the eruption path does not improve within about a year, surgical exposure and orthodontic treatment is indicated.The two different main techniques of surgical exposure in PDCs are the open and the closed techniques. Retrospective studies of the exposure techniques have shown differences in outcomes, which high-lights the need for evidence-based research.The overall aim of this thesis was to compare outcomes of treatment duration, complications and side effects, patients’ perceptions and health economic aspects of the two surgical techniques, in PDCs. Moreover, a comparison of PDC position between the two radiographic methods commonly used in PDC cases; panoramic radiograph and CBCT, aimed to evaluate agreement between the actual measures. This thesis was based on a multicentre randomised controlled trial with two parallel groups, including 120 consecutive patients, aged 9 to 16 years, who were randomly allocated to open or closed surgical exposure. The following conclusions were drawn:The agreement of PDC mesiodistal position was fair (weighted kappa 0.36 (95%CI0.24–0.49) and the mean difference in angle to midline was almost 7˚ (95%CI 5.9˚–7.9˚) higher in panoramic radiographs compared with CBCT. Surgery time, treatment time, root resorption or periodontal measures showed no clinically significant differences between the exposure groups. The open group reported higher pain intensity up to one week post surgery. A higher proportion of bilateral open group cases experienced complications, and weremore frequently wakened at night post surgery. The closed group reported higher pain and discomfort during the orthodontic traction. All PDCs were successfully aligned in the dental arch. A cost-minimization analysis showed no differences in healthcare or societal costs.
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- Björksved, Margitha, 1964-, et al.
(författare)
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Open vs closed surgical exposure of palatally displaced canines: a comparison of clinical and patient-reported outcomes-a multicentre, randomized controlled trial
- 2021
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Ingår i: European Journal of Orthodontics. - : Oxford University Press (OUP). - 0141-5387 .- 1460-2210. ; 43:5, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare treatment time, patients' perceptions during orthodontic treatment, dental fear and side effects, between open and closed surgical exposures in patients with palatally displaced canines (PDCs). Trial design: Multicentre, randomized controlled trial, with random 1:1 allocation of two parallel groups. Materials and methods: One hundred and twenty patients from three different orthodontic centres were randomized into one of the two intervention arms, open or closed surgical exposure. Both techniques had mucoperiosteal flaps raised and bone removed above the PDCs. In open exposure, tissue was removed above the canine, and glass ionomer - reaching above soft tissue - was built on the crown. The canine was then left to erupt spontaneously, prior to orthodontic alignment. At closed exposure, a chain was bonded to the canine and orthodontic traction was applied under the mucosa until eruption. Orthodontic alignment of the canines was undertaken after eruption into the oral cavity, with fixed appliances in both groups. All participants were treated according to intention to treat (ITT). Blinding: Due to the nature of this trial, only outcome assessors could be blinded to the intervention group. Results: One hundred and seventeen patients completed the trial. All PDCs were successfully aligned. Total treatment time was equal in the two techniques, mean difference -0.1 months (95% CI -3.2 to 2.9, P = 0.93). The closed group experienced more pain and discomfort during the active orthodontic traction. Dental fear, root resorption and periodontal status did not show any clinically significant differences between the groups. Generalizability: Results of this randomized controlled trial (RCT) can be generalized only to a similar population aged 9-16 years, if exclusion criteria are met. Conclusion: The closed exposure group experienced more pain and discomfort mostly during active orthodontic traction. All other studied outcomes were similar between the two exposure groups.
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- D'Arcy, Pádraig, et al.
(författare)
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Inhibition of proteasome deubiquitinating activity as a novel cancer therapy
- 2011
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Ingår i: Nature Medicine. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1546-170X .- 1078-8956.
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target. Here we describe the small molecule b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that was insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target.
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- Laurell, Cecilia, et al.
(författare)
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Transcriptional profiling enables molecular classification of adrenocortical tumours
- 2009
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 161:1, s. 141-152
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Tumours in the adrenocortex are common human tumours. Malignancy is however, rare, the yearly incidence being 0.5-2 per million inhabitants, but associated with a very aggressive behaviour. Adrenocortical tumours are often associated with altered hormone production with a variety of clinical symptoms. The aggressiveness of carcinomas together with the high frequency of adenomas calls for a deeper understanding of the underlying biological mechanisms and an improvement of the diagnostic possibilities. Methods: Microarray gene expression analysis was performed in tumours of adrenocortex with emphasis on malignancy as well as hormonal activity. The sample set consisted of 17 adenomas, 11 carcinomas and 4 histological normal adrenocortexes. RNA from these was hybridised according to a reference design on microarrays harbouring 29 760 human cDNA clones. Confirmation was performed with quantitative real time-PCR and western blot analysis. Results: Unsupervised clustering to reveal relationships between samples based on the entire gene expression profile resulted in two subclusters; carcinomas and non-cancer specimens. A large number of genes were accordingly found to be differentially expressed comparing carcinomas to adenomas. Among these were IGF2, FGFR1 and FGFR4 in growth factor signalling the most predominant and also the USP4, UBE2C and UFD1L in the ubiquitin-proteasome pathway. Moreover, two subgroups of carcinomas were identified with different survival outcome, suggesting that survival prediction can be made on the basis of gene expression profiles. Regarding adenomas with aldosterone overproduction, OSBP and VEGFB were among the most up-regulated genes compared with the other samples. Conclusions: Adrenocortical carcinomas are associated with a distinct molecular signature apparent in their gene expression profiles. Differentially expressed genes were identified associated with malignancy, survival as well as hormonal activity providing a resource of candidate genes for an exploration of possible drug targets and diagnostic and prognostic markers.
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- Lindsten, Kristina
(författare)
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Functional studies of the ubiquitin proteasome system using GFP based reporters
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ubiquitin-dependent proteasomal degradation is of paramount importance for cellular processes such as cell cycle progression, transcriptional regulation, apoptosis and disposal of misfolded and aberrant proteins. Moreover the ubiquitin-proteasome system is the main producer of peptides used by major histocompatibility complex class 1 for antigen presentation. Considering its critical involvement in these cellular processes, it is not surprising that aberrant ubiquitin-proteasome-dependent degradation is implicated in human disorders. The aim of this thesis has been to develop reporter systems for quantitative and functional analysis of this system in cells and to use these reporters to gain insight into the interactions between viral and cellular proteins and the ubiquitin- proteasome system. The green fluorescent protein (GFP) was chosen as a reporter for degradation and was in the initial studies modified by the addition of degradation signals that transformed the GFP into a substrate of the proteasome. Upon inhibition of the system the GFP reporters accumulate and the level of obstruction can be monitored by the fluorescence. The GFP reporters were initially characterised and used for studies in cellular systems but more recently we developed a transgenic mouse model constitutively expressing one of the reporters. We used the GFP reporters and new site-specific inhibitors to elucidate the individual contribution of the different proteasomal active sites. Our study demonstrated that the catalytic activities are of unequal importance for degradation. Furthermore this study indicated the presence of a non-catalytic modifier site that regulates the activity of the proteolytic sites through binding of peptides. The role of a cellular and a viral repetitive sequence on proteolysis was also investigated using the GFP reporters. The Epstein-Barr virus derived Gly-Ala repeat functions as a stabilising domain. We concluded that it protects a protein from degradation in a length-dependent manner. Another repetitive sequence with a length-dependent effect is the poly-GIn repeat, which is expanded in several proteins involved in neurodegeneration. We showed that in contrast to the Gly-Ala repeat this repeat stabilises proteins through the formation of insoluble aggregates. Another protein associated with neurodegeneration, and that also colocalises with different aggregates involved in such diseases, is the transcript mutant of ubiquitin, UBB+1. With the use of the GFP reporters we demonstrated that UBB+1 is a substrate of the proteasome and is ubiquitinated in a specific manner and this causes all inhibition of the ubiquitin-proteasome system. It remains to be resolved if this inhibitory activity contributes to neuropathogenesis. Together these studies shed some light on the roles of the ubiquitin-proteasome system in normal and pathologic conditions. The cellular and transgenic animal models presented in this thesis will be important tools for further studies on this intriguing proteolytic system.
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