| 1. |
- Benson, Mikael, 1954, et al.
(författare)
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DNA microarray analysis of chromosomal susceptibility regions to identify candidate genes for allergic disease: A pilot study
- 2004
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 124:7, s. 813-819
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To examine whether DNA microarray analysis of chromosomal susceptibility regions for allergy can help to identify candidate genes. Material and Methods-Nasal biopsies were obtained from 23 patients with allergic rhinitis and 12 healthy controls. RNA was extracted from the biopsies and pooled into three patient and three control pools. These were then analysed in duplicate with DNA microarrays containing 12626 genes. Candidate genes were further examined in nasal biopsies (real-time polymerase chain reaction) and blood samples (single nucleotide polymorphisms) from other patients with allergic rhinitis and from controls. Results-A total of 37 differentially expressed genes were identified according to criteria involving both the size and consistency of the gene expression levels. The chromosomal location of these genes was compared with the chromosomal susceptibility regions for allergic disease. Using a statistical method, five genes were identified in these regions, including serine protease inhibitor, Kazal type, 5 (SPINK5) and HLA-DRB2. The relevance of these genes was examined in other patients with allergic rhinitis and in controls; none of the genes were differentially expressed in nasal biopsies. Moreover, no association between allergic rhinitis and SPINK5 polymorphisms was found, at either the genotype or haplotype level. Conclusions-DNA microarray analysis of chromosomal susceptibility regions did not lead to identification of candidate genes that could be validated in a new material. However, because gene polymorphisms may cause differential gene expression, further studies, including validation data, are needed to examine this approach.
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| 2. |
- Bergman, Annika, et al.
(författare)
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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.
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| 3. |
- Bergman, Annika, et al.
(författare)
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The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation
- 2001
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 9:10, s. 787-793
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Tidskriftsartikel (refereegranskat)abstract
- The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cΜ. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cΜ was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the Pexcess and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.
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| 4. |
- Einbeigi, Zakaria, 1962, et al.
(författare)
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Occurrence of both breast and ovarian cancer in a woman is a marker for the BRCA gene mutations: a population-based study from western Sweden.
- 2007
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Ingår i: Familial cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This study aimed to analyze whether the occurrence of both breast and ovarian cancer in a woman serves as a marker for BRCA gene mutations. MATERIAL AND METHODS: This population-based study included 256 women in western Sweden who developed both invasive breast and ovarian tumors between 1958 and 1999. Archival paraffin tissue blocks of their tumors were retrieved for DNA-extraction to analyze the founder mutation, BRCA1 c.3171_3175dup (c.3171ins5), which is most common in this geographic area and four other common Scandinavian BRCA1 gene mutations and one BRCA2 mutation. Together, account these mutations for approximately 75% of the BRCA1/2 gene mutations in the clinical unit. RESULTS: Ninteen percent (95% confidence interval (CI) 14-24%) of the women carried one of the analyzed BRCA1 gene mutations but none of the women were positive for the analyzed BRCA2 mutation. One-third of the women with both tumors before age 60 were mutation carriers. BRCA1 c.3171_3175dup (c.3171ins5) constituted 84% of all identified mutations. Although the majority of breast cancers were invasive ductal and atypical medullary types, a variety of other breast malignancies were seen among mutation carriers. Serous ovarian carcinomas predominated among ovarian tumors. A variety of other ovarian tumors, including three granulosa-theca cell tumors, were also observed among mutation carriers. CONCLUSIONS: The occurrence of both breast and ovarian cancer in a woman is associated with a high likelihood of a constitutional BRCA1 mutation. These women and their families might therefore be considered for mutation screening after appropriate genetic counselling.
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| 5. |
- Lindahl, Bertil, et al.
(författare)
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An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay
- 2017
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:2, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.
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| 6. |
- Ljung, Lina, et al.
(författare)
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A Rule-Out Strategy Based on High-Sensitivity Troponin and HEART Score Reduces Hospital Admissions
- 2019
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Ingår i: Annals of Emergency Medicine. - : MOSBY-ELSEVIER. - 0196-0644 .- 1097-6760. ; 73:5, s. 491-499
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Tidskriftsartikel (refereegranskat)abstract
- Study objective: We evaluate whether a combination of a 1-hour high-sensitivity cardiac troponin algorithm and History, ECG, Age, Risk Factors, and Troponin (HEART) score reduces admission rate (primary outcome) and affects time to discharge, health care-related costs, and 30-day outcome (secondary outcomes) in patients with symptoms suggestive of an acute coronary syndrome.Methods: This prospective observational multicenter study was conducted before (2013 to 2014) and after (2015 to 2016) implementation of a strategy including level of high-sensitivity cardiac troponin T or I at 0 and 1 hour, combined with the HEART score. Patients with a nonelevated baseline high-sensitivity cardiac troponin level, a 1-hour change in high-sensitivity cardiac troponin T level less than 3 ng/L, or high-sensitivity cardiac troponin I level less than 6 ng/L and a HEART score less than or equal to 3 were considered to be ruled out of having acute coronary syndrome. A logistic regression analysis was performed to adjust for differences in baseline characteristics.Results: A total of 1,233 patients were included at 6 centers. There were no differences in regard to median age (64 versus 63 years) and proportion of men (57% versus 54%) between the periods. After introduction of the new strategy, the admission rate decreased from 59% to 33% (risk ratio 0.55 [95% confidence interval {CI} 0.48 to 0.63]; odds ratio 0.33 [95% CI 0.26 to 0.42]; adjusted odds ratio 0.33 [95% CI 0.25 to 0.42]). The median hospital stay was reduced from 23.2 to 4.7 hours (95% CI of difference -20.4 to -11.4); median health care-related costs, from $1,748 to $1,079 (95% CI of difference -$953 to -$391). The number of clinical events was very low.Conclusion: In this before-after study, clinical implementation of a 1-hour high-sensitivity cardiac troponin algorithm combined with the HEART score was associated with a reduction in admission rate and health care burden, with very low rates of adverse clinical events.
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| 7. |
- Ljung, Lina, et al.
(författare)
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Sensitivity of undetectable level of high-sensitivity troponin T at presentation in a large non-ST-segment elevation myocardial infarction cohort of early presenters
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 284, s. 6-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to evaluate the diagnostic sensitivity for myocardial infarction (MI) when using an undetectable level of high-sensitivity cardiac troponin T (hs-cTnT < 5 ng/L) at presentation combined with a non-ischemic electrocardiogram (ECG), to rule out MI in a non-ST-segment elevation MI (NSTEMI) cohort presenting ≤2 h from symptom onset. We also aimed to compare baseline characteristics and 30-day outcome in NSTEMI patients presenting with and without hs-cTnT < 5 ng/L.METHODS: All patients admitted to five centers in Sweden 2011-2015, after the introduction of hs-cTnT, who presented ≤2 h from symptom onset and received a final diagnosis of NSTEMI, were identified through the SWEDEHEART registry. These data and data of hs-cTnT levels were verified in the hospitals' medical records. The registry provided baseline and outcome data.RESULTS: Twenty-four (2.6%) of 911 NSTEMI patients presented with hs-cTnT < 5 ng/L. In patients presenting >1-≤2 h from symptom onset the sensitivity for MI when combining hs-cTnT and ECG was 99.4% (95% CI 98.4%-99.8%). In patients presenting ≤1 h, and in patients aged ≤65 years without prior MI, the sensitivity was insufficient. NSTEMI patients presenting with hs-cTnT < 5 ng/L were younger and had less often a prior MI. A total of 62.5 vs. 63.5% of the NSTEMI patients presenting with and without hs-cTnT < 5 ng/L underwent revascularization within 30 days and 4.5 and 3.2% died respectively.CONCLUSIONS: Hs-cTnT < 5 ng/L at presentation combined with a non-ischemic ECG may be used to rule out MI in patients presenting as early as >1 h from symptom onset with a sufficient sensitivity.
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| 8. |
- Löfmark, Henrik, et al.
(författare)
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HEART-score can be simplified without loss of discriminatory power in patients with chest pain : Introducing the HET-score
- 2023
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Ingår i: American Journal of Emergency Medicine. - : Elsevier. - 0735-6757 .- 1532-8171. ; 74, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe History, Electrocardiogram (ECG), Age, Risk factors and Troponin, (HEART) score is useful for early risk stratification in chest pain patients. The aim was to validate previous findings that a simplified score using history, ECG and troponin (HET-score) has similar ability to stratify risk.MethodsPatients presenting with chest pain with duration of ≥10 min and an onset of last episode ≤12 h but without ST-segment elevation on ECG at 6 emergency departments were eligible for inclusion. The HEART-score and the simplified HET-score were calculated. The endpoint was a composite of myocardial infarction (MI) as index diagnosis, readmission due to new MI or death within 30 days.ResultsHEART-score identified 32% as low risk (0-2p), 47% as intermediate risk (3-5p), and 20% as high risk (6-10p) patients. The endpoint occurred in 0.5%, 7.3% and 35.7%, respectively. HET-score identified 39%, 42% and 19% as low- (0p), intermediate- (1-2p) and high-risk (3-6p) patients, with the endpoint occurring in 0.6%, 6.2% and 43.2%, respectively.When all variables included in the HEART-score were included in a multivariable logistic regression analysis, only History (OR, CI [95%]): 2.97(2.16–4.09), ECG (1.61[1.14–2.28]) and troponin level (5.21[3.91–6.95]) were significantly associated with cardiovascular events. When HEART- and HET-score were compared in a ROC-analysis, HET-score had a significantly larger AUC (0.887 vs 0.853, p < 0.001).ConclusionsCompared with HEART-score, HET-score is simpler and appears to have similar ability to discriminate between chest pain patients with and without cardiovascular event.
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| 9. |
- Pettersson, Anna, et al.
(författare)
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Experiences of a One-hour Algorithm in Chest Pain Patients With a Nonelevated Troponin T at Presentation.
- 2018
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Ingår i: Critical Pathways in Cardiology. - 1535-282X .- 1535-2811. ; 17:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate the use of a 1-hour measurement of high-sensitivity cardiac troponin T (hs-cTnT) in an emergency department (ED) population of chest pain patients with a nonelevated baseline hs-cTnT and to examine the prevalence of early dynamic changes in hs-cTnT and the association with admission rate, diagnosis, and outcome.Methods: All patients with a chief complaint of chest pain presenting to the ED of Karolinska University Hospital, Solna, Sweden, from December 2014 to September 2015 who had a baseline hs-cTnT of ≤14 ng/L and a second value obtained within >30 to ≤90 minutes were followed for 30 days regarding admission, readmission, myocardial infarction (MI), and death.Results: A total of 1091 patients were included. Dynamic 1-hour changes in hs-cTnT defined as an increase or decrease of ≥3 ng/L occurred in 23 patients (2.1%). Fifteen patients (65.2%) in the dynamic group were admitted, compared with 148 patients (13.9%) in the nondynamic group (P < 0.001). Four of the admitted patients (26.7%) in the dynamic and 1 (0.7%) in the nondynamic group were diagnosed with an MI (P < 0.001). No death or MI occurred within 30 days among those discharged from the ED.Conclusions: Dynamic 1-hour changes in hs-cTnT were uncommon but associated with a higher rate of admission and of MI in an unselected population of chest pain patients with a nonelevated hs-cTnT at presentation. Lack of dynamic changes makes MI highly unlikely, and a 1-hour measurement may facilitate an early rule out of MI but should be used together with clinical assessment.
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| 10. |
- Pikkarainen, Harri V S, et al.
(författare)
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On-line solid debris analysis of oil using vision technology on open computing platform
- 2009
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Ingår i: 6th International Conference on Condition Monitoring and Machinery Failure Prevention Technologies 2009. - 9781618390097 ; , s. 320-331
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Konferensbidrag (refereegranskat)abstract
- This article describes a case-study related to on-line condition monitoring measurements in process industry. A platform for on-line, real-time and remotely operated condition monitoring has been developed. The system consists of an open source based embedded and cost effective DSP computing platform, a machine vision sensor for solid debris analysis of oils, and interfaces for other measurement technologies (e.g. vibration analysis and/or temperature measurements). In addition, the platform is equipped with data transmission interface that enables remote operation and control. Real-time analysis of solid particles in oil is useful in many preventive condition monitoring applications, for example, in the lubrication circuit of a paper machine or with cold rolling lubrication oils. In the case of a paper machine the generated information can be used to pinpoint upcoming failures in the machine elements (e.g. bearings, gears etc.). Whereas in the case of cold rolling applications the information is useful to prevent quality problems in the rolled metal product. In the both applications the presented system enables also monitoring failures in the filtration system. Preliminary results and designs show that the system is able to detect and analyse size and shape for particles larger than 50 micrometers continuously with a frame rate of 5 Hz from the oil flow volume of 13.8 ml/s and flow speed of 60 mm/s. The system is in progress of being further developed in collaboration with the industry. Easy integration of different sensors and real-time measurements make the system a powerful tool for making maintenance decisions in process industry
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