| 1. |
- Lindstrand, Anna, et al.
(författare)
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Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability
- 2022
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Ingår i: Genetics in Medicine. - : ELSEVIER SCIENCE INC. - 1098-3600 .- 1530-0366. ; 24:11, s. 2296-2307
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. Methods: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). Results: The diagnostic yield was 35% (GS -first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. Conclusion: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time-and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 2. |
- Norlin, Maria, et al.
(författare)
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Drug-mediated gene regulation of vitamin D3 metabolism in primary human dermal fibroblasts
- 2017
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 120:1, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catabolic reactions (CYP24A1). The cells produced both 25-hydroxyvitamin D3 and 1a,25-dihydroxyvitamin D3. The results demonstrate that primary dermal fibroblasts have an active vitamin D3 metabolising system. High incidence of low bone mineral density is a concern for HIV-infected patients treated with antiretroviral drugs. Osteomalacia and severe vitamin D deficiency have been reported. We investigated whether drug-mediated gene regulation could be a possible mechanism behind these adverse drug effects. Fibroblasts were treated with different drugs used in HIV therapy and the 1a,25-dihydroxyvitamin D3 levels and relative mRNA-levels for crucial enzymes were determined. Efavirenz, stavudine and ritonavir significantly downregulated the bioactivating CYP2R1 and upregulated the catabolic CYP24A1. The drugs reduced bioactivating enzyme activities and cellular levels of 1a,25-dihydroxyvitamin D3. The current results indicate that effects on gene expression may lead to disturbed vitamin D-metabolism and decreased cellular levels of active vitamin D3. The data are consistent with the impaired bone health in patients treated with certain antiretroviral drugs.
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| 3. |
- Alkhateeb, Noor, et al.
(författare)
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Patient-perceived features and clinical characteristics of tooth pain : A comparison between apical periodontitis and persistent dento-alveolar pain disorder (PDAP) – preliminary results
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Differential diagnosis between tooth pain of inflammatory and neuropathic origin is crucial since treatment strategies differ. Aim: Evaluate and compare self-reported and clinically observed pain characteristics in patients with SAP (symptomatic apical periodontitis) and PDAP (persistent dento-alveolar pain disorder). Methodology: Patients diagnosed with SAP and PDAP were recruited from Malmö University and Folktandvården Östergötland. Data collection included clinical examination and questionnaire (tooth pain characteristics, verbal pain description [short-form McGill Pain Questionnaire; SF-MPQ], factors affecting the pain). Results: Data from 24 patients with SAP and 20 with PDAP (24 females, mean age 53 years) were analyzed. Average pain intensity was 4.4 (0–10 numeric rating scale) and average duration 1527 days. 64% reported continuous and 27% recurrent pain. 58% of teeth were tender to percussion and 66% to apical palpation. 27% reported concurrent pain from jaw muscles/joints. Significant differences were found for gender (% females; PDAP>SAP;p=0.013), pain duration (PDAP>SAP;p<0.0001), pain frequency (PDAP>SAP;p<0.001), percussion tenderness (SAP>PDAP;p=0.012), muscle/joint pain (PDAP>SAP;p=0.021). SF-MPQ and affecting factors did not differ (p=0.096–1.000). Conclusion: Preliminary results indicate that pain intensity, pain description and factors affecting the pain are similar for SAP and PDAP. Female gender, long pain duration, high pain frequency, and concurrent muscle/joint pain presented more frequently in PDAP.
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| 4. |
- Alstergren, Per, et al.
(författare)
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Clinical diagnosis of temporomandibular joint arthritis
- 2018
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 45:4, s. 269-281
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push-pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL-1, IL-1ra, IL-1sRII, IL-6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non-arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P<.001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P<.001) and higher number of painful mandibular movements (P=.004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.
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| 5. |
- Baad-Hansen, Lene, et al.
(författare)
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Chair-side intraoral somatosensory examination in patients with atypical odontalgia and healthy subjects
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Chair-side intraoral somatosensory examination in patients with atypical odontalgia and healthy subjects L Baad-Hansen, M Pigg, S Elmasry Ivanovic, H Faris, T List, M Drangsholt, P Svensson Aim of investigation: In patients with persistent orofacial pain, assessment of somatosensory function is recommended. A chair-side qualitative examination with good reliability revealing signs of hyper-/hyposensitivity to touch, cold and painful pinprick stimulation may be performed. The aim of this multicenter study was to compare three qualitative measures of intraoral somatosensory function between patients with atypical odontalgia (AO) and healthy subjects. Methods: 31 AO patients (6 male, 25 female; mean age: 54±13) and 47 healthy age- and sex-matched controls (15 male, 32 female: mean age: 47±12) were recruited from Malmö University (Sweden), University of Washington (USA) and Aarhus University (Denmark). In AO patients, sensitivity to touch, cold, and pinprick stimuli was evaluated on the buccal gingiva adjacent to the painful site and the corresponding contralateral ‘mirror-image’ gingival site. In healthy subjects, tests were performed bilaterally on the buccal gingiva adjacent to the first maxillary premolars. Patients were asked to report hyper-, hypo-, or normo-sensitivity/- algesia to touch, cold and painful stimuli on the painful site compared with the contralateral site; healthy subjects were asked to compare sensitivity between sides. Χ2-tests were used to analyze differences in frequency of hyper-, hyposensitivity or normosensitivity between groups. Results: The frequency of subjectively reported normosensitivity to all stimulus modalities were significantly lower in patients (23-58%) than in healthy subjects (68-91%), P<0.001. Frequency of hypersensitivity to all modalities were significantly higher in patients (29-61%) than in controls (9-17%), P<0.015, whereas reports of hyposensitivity were similar between groups (2-16%), P>0.054. Conclusion: A quick and simple chair-side evaluation of intraoral somatosensory function can detect intraoral sensory disturbances in AO patients, mainly in the form of hyper-sensitivity. These tests may be useful in the initial screening of patients with persistent orofacial pain.
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| 6. |
- Baad-Hansen, Lene, et al.
(författare)
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Chairside intraoral qualitative somatosensory testing : reliability and comparison between patients with atypical odontalgia and healthy controls
- 2013
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Ingår i: Journal of Orofacial Pain. - : Quintessence. - 1064-6655 .- 1945-3396. ; 27:2, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess intraoral inter- and intraexaminer reliability of three qualitative measures of intraoral somatosensory function and to compare these measures between patients with atypical odontalgia (AO) and healthy controls. METHODS: Thirty-one AO patients and 47 healthy controls participated. Inter- and intraexaminer reliability was tested on a subgroup of 46 subjects (25 AO; 21 healthy). Sensitivity to touch, cold, and pinprick stimuli was evaluated on the painful gingival site and the corresponding contralateral site in AO patients, and bilaterally on the gingiva of the first maxillary premolars in controls. Patients were asked to report hypersensitivity, hyposensitivity, or normal sensitivity to stimuli on the painful site compared with the nonpainful site. Kappa values were calculated, and chi-square and Fisher's exact tests were used to compare frequencies between groups. RESULTS: Kappa values ranged between 0.63 and 0.75. The frequency of hypersensitivity to either modality was significantly higher in patients (29% to 61%) than in controls (9% to 17%) (P < .015), whereas reports of hyposensitivity were similar between groups (2% to 16%) (P > .057). Only 3.2% of the AO patients had no reports of abnormal sensitivity on any of the tests, compared with 59.6% of the healthy subjects (P < .001). CONCLUSION: Intraoral qualitative somatosensory testing can detect intraoral sensory disturbances in AO patients, and the reliability is sufficient for initial screening of orofacial somatosensory function.
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| 7. |
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| 8. |
- Baad-Hansen, Lene, et al.
(författare)
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Intraoral somatosensory abnormalities in patients with atypical odontalgia : a controlled multicenter quantitative sensory testing study
- 2013
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Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 154:8, s. 1287-1294
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Tidskriftsartikel (refereegranskat)abstract
- Intraoral somatosensory sensitivity in patients with atypical odontalgia (AO) has not been investigated systematically according to the most recent guidelines. The aims of this study were to examine intraoral somatosensory disturbances in AO patients using healthy subjects as reference, and to evaluate the percent agreement between intraoral quantitative sensory testing (QST) and qualitative sensory testing (QualST). Forty-seven AO patients and 69 healthy control subjects were included at Universities of Washington, Malmö, and Aarhus. In AO patients, intraoral somatosensory testing was performed on the painful site, the corresponding contralateral site, and at thenar. In healthy subjects, intraoral somatosensory testing was performed bilaterally on the upper premolar gingiva and at thenar. Thirteen QST and 3 QualST parameters were evaluated at each site, z-scores were computed for AO patients based on the healthy reference material, and LossGain scores were created. Compared with control subjects, 87.3% of AO patients had QST abnormalities. The most frequent somatosensory abnormalities in AO patients were somatosensory gain with regard to painful mechanical and cold stimuli and somatosensory loss with regard to cold detection and mechanical detection. The most frequent LossGain code was L0G2 (no somatosensory loss with gain of mechanical somatosensory function) (31.9% of AO patients). Percent agreement between corresponding QST and QualST measures of thermal and mechanical sensitivity ranged between 55.6% and 70.4% in AO patients and between 71.1% and 92.1% in control subjects. In conclusion, intraoral somatosensory abnormalities were commonly detected in AO patients, and agreement between quantitative and qualitative sensory testing was good to excellent.
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| 9. |
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| 10. |
- Baad-Hansen, Lene, et al.
(författare)
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Reliability of intra-oral quantitative sensory testing (QST) in patients with atypical odontalgia and healthy controls : a multicentre study
- 2015
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 42:2, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- The reliability of comprehensive intra-oral quantitative sensory testing (QST) protocol has not been examined systematically in patients with chronic oro-facial pain. The aim of the present multicentre study was to examine test-retest and interexaminer reliability of intra-oral QST measures in terms of absolute values and z-scores as well as within-session coefficients of variation (CV) values in patients with atypical odontalgia (AO) and healthy pain-free controls. Forty-five patients with AO and 68 healthy controls were subjected to bilateral intra-oral gingival QST and unilateral extratrigeminal QST (thenar) on three occasions (twice on 1 day by two different examiners and once approximately 1 week later by one of the examiners). Intra-class correlation coefficients and kappa values for interexaminer and test-retest reliability were computed. Most of the standardised intra-oral QST measures showed fair to excellent interexaminer (9-12 of 13 measures) and test-retest (7-11 of 13 measures) reliability. Furthermore, no robust differences in reliability measures or within-session variability (CV) were detected between patients with AO and the healthy reference group. These reliability results in chronic orofacial pain patients support earlier suggestions based on data from healthy subjects that intra-oral QST is sufficiently reliable for use as a part of a comprehensive evaluation of patients with somatosensory disturbances or neuropathic pain in the trigeminal region.
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