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- Pegelow, M., et al.
(author)
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Reliability and Predictive Validity of Dental Arch Relationships Using the 5-Year-Olds’ Index and the GOSLON Yardstick to Determine Facial Growth
- 2021
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In: Cleft Palate-Craniofacial Journal. - : SAGE Publications. - 1055-6656 .- 1545-1569. ; 58:5, s. 619-627
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Journal article (peer-reviewed)abstract
- Aims: To determine reliability and predictive validity of the 5-year-olds’(5YO) Index and GOSLON Yardstick in 119 patients born with unilateral cleft lip and palate at 5, 7/8, 10, 15/16, and 19 years. Methods: Five hundred thirty-four dental study models were appraised by 2 teams in 2 centers, twice in each center. Intrateam and interteam reliability in scoring the models was calculated using κ. Dental arch prediction rates were calculated as the proportion of models remaining in the same category (good–scores 1 and 2; fair–score 3; poor–scores 4 and 5) over time. Results: Intrateam and interteam κ statistics ranged from 0.74 to 0.89 and from 0.74 to 0.81, respectively. The 5YO Index and GOSLON Yardstick at 5 years produced almost identical results. The prediction rate of 19-year-old (n = 106) outcome was >80% for those in groups 1 and 2 at 5 years, while for those in groups 4 and 5 prediction was poor (<40%). Prediction of groups 4 and 5 remained poor until 10 years when it increased to 77%. At 15/16 years prediction rate was 93% for those in groups 4 and 5. Prediction of cases in group 3 was very poor at all ages. Conclusions: These results question the predictive value of “poor” dental arch relationships before 10 years of age. However, the predictive value of “good” dental arch relationship scores over time is good in all age groups. This has implications for audit policies to predict facial growth outcomes. © American Cleft Palate-Craniofacial Association. All rights reserved 2020.
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- Pegelow, M., et al.
(author)
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Validation of reported dentoalveolar relationships in the Swedish Quality Registry for Cleft Lip and Palate
- 2020
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In: European journal of orthodontics. - : Oxford University Press (OUP). - 1460-2210 .- 0141-5387. ; 42:1, s. 30-35
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The present study validated data that had been reported to the Swedish Quality Registry for Cleft Lip and Palate (CLP) under new requirements from 2016, when use of the 5-year-old (5YO) and the Modified Huddart and Bodenham (MHB) indices for rating occlusion in children born with unilateral CLP (UCLP) was introduced. MATERIALS AND METHODS: The sample included blinded study casts (n = 97) and photos (n = 4) of 5-year-old children who had been born with UCLP in 2009-2011 and were enrolled at one of six cleft centres in Sweden. Fourteen orthodontists from the centres assessed the patients (n = 101) using the 5YO and the MHB indices. Median 5YO and MHB scores of the 14 assessments were compared with original registry data (n = 61). Each centre devised code keys to protect the identities of their patients in the registry. RESULTS: Interrater agreement among the 14 orthodontists was good for the 5YO index (quadratic-weighted kappa: 0.72-0.92) and the MHB index (intraclass correlation coefficient: 0.991-0.994). Comparisons of median 5YOs for each identifiable child with their registry data (n = 61) found total agreement for 70.5 per cent. Comparisons between median MHBs and registry data showed very good or good agreement in 93.4 per cent of the cases. LIMITATIONS: Two teams lost their code keys, which reduced the sample to 61 patients. CONCLUSIONS: The dentoalveolar outcome data in the CLP registry was trustworthy. There was good agreement among the Swedish cleft teams assessing the 5YO and MHB indices in children born with UCLP at age 5 years. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Orthodontic Society.
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3. |
- Peterson, P, et al.
(author)
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Mean GOSLON Yardstick Scores After 3 Different Treatment Protocols-A Long-term Study of Patients With Unilateral Cleft Lip and Palate
- 2019
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In: The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. - : SAGE Publications. - 1545-1569. ; 56:2, s. 236-247
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Journal article (peer-reviewed)abstract
- (1) To evaluate dental arch relationships, with the Great Ormond Street, London and Oslo (GOSLON) Yardstick, of participants with Unilateral cleft lip and palate (UCLP) and treated with 1-stage palatal closure with 3 different surgical protocols (2) to compare the mean GOSLON ratings with other CLP centers. Design: Retrospective study of medical charts and dental models. Setting: Karolinska University Hospital, Stockholm, Sweden. Participants: Eighty-seven patients with UCLP operated with 1-stage palatal repair. Thirty-five were operated with Veau-Wardill-Kilner (VWK) technique 1975 to 1986, 31 with minimal incision technique (MIT) from 1987 to 1997, and 21 according to MIT with muscle reconstruction (MITmr) 1998 to 2004. Interventions: Dental casts at ages 5 (n = 87), 7 to 8 (n = 27), 10 (n = 81), 16 (n = 61), and 19 (n = 35) years were rated by 10 assessors with the GOSLON Yardstick. Information of other interventions was retrieved from patients’ charts. Main outcome measures: Mean GOSLON ratings. Results: A total of 82% of the participants were rated as having excellent to satisfactory outcome. Weighted κ statistics for the 10 assessors was good for inter-rater agreement and good/very good for intra-rater agreement. Conclusions: The mean GOSLON score in the Stockholm overall material at age 10 was 2.67. The VWK technique resulted in a greater need of orthognathic surgery than the MIT ( P < .01). The MITmr did not produce better dental arch relationships than MIT at age 5 ( P < .05). The best dental arch relationships were found in the MIT group at 10 years, mean 2.58, which is not significantly different from other centers with excellent outcome except Gothenburg and Vienna.
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4. |
- Kadi, H, et al.
(author)
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A CBCT Based Assessment of Canine Eruption and Development Following Alveolar Bone Grafting in Patients Born With Unilateral Cleft lip and/or Palate
- 2023
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In: The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. - : SAGE Publications. - 1545-1569. ; 60:4, s. 386-394
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Journal article (peer-reviewed)abstract
- To three-dimensionally assess and visualize the eruption path and development of the maxillary canine following alveolar bone grafting in patients born with cleft lip and palate. A further objective of this analysis was to assess how the presence of the lateral incisor impacts the eruption path of the canine. Observational follow-up study. Stockholm Craniofacial Team, Karolinska University Hospital, Sweden. Thirty children born with non-syndromic unilateral cleft lip with or without palate were consecutively included. CBCT scans of the maxilla were taken six months before and six months after the alveolar bone-grafting surgery for each patient. Canine eruption (angulation and vertical movement) and canine development (length and volume). There was a significant difference pre- and post-operatively of the canine angulation between the cleft and non-cleft sides. The mean angulation on the cleft side was 14.7° (SD = 11.1°) while on the non-cleft side, it was 4.9° (SD = 9.2°). No significant differences were noted between cleft-side and non-cleft side canines in terms of amount of vertical eruption and volumetric development. Absence of the lateral incisor did not significantly contribute to either canine angulation or its vertical eruption on the cleft-side. Higher angulation of the canine on the cleft side indicates a higher risk of future canine impaction. Presence or absence of the lateral incisor did not significantly affect canine angulation or its vertical eruption. Increased age and children born with total cleft lip and palate imply a higher risk of angulated canines on the cleft side.
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- Baghdasaryan, A., et al.
(author)
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Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis
- 2016
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In: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 64:3, s. 674-681
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Journal article (peer-reviewed)abstract
- Background and Aims: Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury. Methods: Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. Liver injury was assessed biochemically and histologically after 4 weeks of A4250 treatment. Expression profiles of genes involved in BA homeostasis, inflammation and fibrosis were assessed via RT-PCR from liver and ileum homogenates. Intestinal inflammation was assessed by RNA expression profiling and immunohistochemistry. Bile flow and composition, as well as biliary and fecal BA profiles were analyzed after 1 week of ASBT inhibitor feeding. Results: A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of proinflammatory (Tnf-alpha, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3- and biliary phospholipid secretion resulting in an increased HCO3-/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-beta-muricholic acid and taurocholic acid. Conclusions: Pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA concentrations in mice. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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- Lemberger, T., et al.
(author)
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CREB has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis
- 2008
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In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 22:8, s. 2872-2879
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Journal article (peer-reviewed)abstract
- Induction of specific gene expression patterns in response to activity confers functional plasticity to neurons. A principal role in the regulation of these processes has been ascribed to the cAMP responsive element binding protein (CREB). Using genomewide expression profiling in mice lacking CREB in the forebrain, accompanied by deletion of the cAMP responsive element modulator gene (CREM), we here show that the role of these proteins in activity-induced gene expression is surprisingly selective and highly context dependent. Thus, only a very restricted subset of activity-induced genes (i.e., Gadd45b or Nr4a2) requires these proteins for their induction in the hippocampus after kainic acid administration, while they are required for most of the cocaine-induced expression changes in the striatum. Interestingly, in the absence of CREB, CREM is able to rescue activity-regulated transcription, which strengthens the notion of overlapping functions of the two proteins. In addition, we show that cholesterol metabolism is dysregulated in the brains of mutant mice, as reflected coordinated expression changes in genes involved in cholesterol synthesis and neuronal accumulation of cholesterol. These findings provide novel insights into the role of CREB and CREM in stimulus-dependent transcription and neuronal homeostasis. © FASEB.
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11. |
- Lemberger, Ursula J, et al.
(author)
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Hepatocyte specific expression of an oncogenic variant of β-catenin results in cholestatic liver disease.
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:52, s. 86985-86998
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Journal article (peer-reviewed)abstract
- The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive.Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice. The primary bile acid synthesis enzyme Cyp7a1 was increased whereas Cyp27 and Cyp8b1 were reduced in Ctnnb1CA hep mice. Expression of compensatory bile acid transporters including Abcb1, Abcb4, Abcc2 and Abcc4 were significantly increased in Ctnnb1CA hep mice while Ntcp was reduced. Accompanying changes of bile acid transporters favoring excretion of bile acids were observed in intestine and kidneys of Ctnnb1CA hep mice. Additionally, disturbed bile acid regulation through the FXR-FGF15-FGFR4 pathway was observed in mice with activated β-catenin.Mice with a loxP-flanked exon 3 of the Ctnnb1 gene were crossed to Albumin-Cre mice to obtain mice with hepatocyte-specific expression of a dominant stable form of β-catenin (Ctnnb1CA hep mice). Ctnnb1CA hep mice were analyzed by histology, serum biochemistry and mRNA profiling.Expression of a dominant stable form of β-catenin in hepatocytes results in severe cholestasis and biliary type fibrosis.
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12. |
- Neovius, E., et al.
(author)
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Alveolar bone healing accompanied by severe swelling in cleft children treated with bone morphogenetic protein-2 delivered by hydrogel
- 2013
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In: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier BV. - 1748-6815 .- 1878-0539. ; 66:1, s. 37-42
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Journal article (peer-reviewed)abstract
- Background: The use of osteoinductive growth factors may be preferable for alveolar cleft repair because it eliminates the need of bone harvesting. In the present prospective randomised pilot study, patients with alveolar clefts were treated with either bone morphogenetic protein 2 (BMP-2) delivered by a hyaluronan-based hydrogel or autologous bone from the iliac crest. Methods: Seven patients with cleft lip or cleft lip and palate were included. Computed tomography (CT) was performed preoperatively and 6 months postoperatively. The residual cleft volume was compared with the initial volume. Surgery time, bleeding and hospital stay were compared between the two groups. Results: Four patients were randomised to treatment with BMP-2. A low BMP-2 concentration of 50 μg ml-1 hydrogel did not induce bone formation in treated patients (n = 2) after 6 months, as seen by CT scans. Therefore, the BMP-2 concentration was raised to 250 μg ml-1 hydrogel in the subsequently randomised patients (n = 2). Bone formation with volume ratio of 59% and 33% was here verified by CT scans after 6 months. However, a severe gingival swelling appeared during the first week in patients treated with higher BMP-2 doses. In the autologous bone group (n = 3), the volume ratio was 29%, 48%, and 69%. Mean surgery time was 100 min in the BMP-2 group and 123 min in the autologous bone group. The mean hospital stay was 2.75 and 3.33 days, respectively. Conclusions: BMP-2 at a concentration of 250 μg ml-1 delivered by a hydrogel can be used to treat alveolar cleft defects with good bone quantity and comparable to autologous bone grafts. However, severe gingival swelling may limit the use of BMP-2 for these patients. Therefore, the study was prematurely closed.
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