| 41. |
- Hammarsten, Ola, et al.
(författare)
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Troponinnivåer ger nu bättre hjälp vid misstänkt hjärtinfarkt - Låga nivåer kan med hög säkerhet utesluta hjärtinfarkt : nya analysmetoder ökar den medicinska säkerheten
- 2017
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of troponin levels on the emergency ward Patients with myocardial infarction are at a high risk of sudden death and new cardiovascular events. For this reason, it is important to identify these patients and device treatment to reduce the risk. Patients who seek care with symptoms indicative of myocardial infarction, mainly chest pain, constitute a large proportion of patients at our emergency departments. However, only 5-10 % of these patients have myocardial infarction, whereas the majority has benign causes of their symptoms. This means that it is important not only to identify patients with myocardial infarction quickly, but also to rule out myocardial infarction and other serious disease as fast and safely as possible. With the aid of assays capable of measuring low levels of the cardiac damage biomarker troponin, so-called high-sensitive troponin assays, and several large high-quality clinical studies, myocardial infarction can now be ruled out safely and quickly. If the patient presents with a troponin T level below 5 ng/L and has a normal ECG, myocardial infarction can normally be ruled out without the need for further investigation. In this way, about 30 % of all patients who present with a suspected myocardial infarction can leave the emergency room quickly with a high degree of medical security. On the other hand, when patients present with troponin T levels above 40 ng/L, the patient should normally be admitted to the hospital. These patients are a high-risk group and constitute only 6 % of those who seek medical attention with a suspected myocardial infarction.
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| 42. |
- Hammarsten, Ola, et al.
(författare)
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Use of the cell division assay to diagnose Fanconi anemia patients' hypersensitivity to mitomycin C
- 2021
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Ingår i: Cytometry Part B-Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 100:3
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Tidskriftsartikel (refereegranskat)abstract
- The recently reported cell division assay (CDA) was optimized to measure the relative sensitivity of cells to cytotoxic drugs in vitro. Here, we investigated the in vitro hypersensitivity of lymphocytes from Fanconi anemia (FA) patients, to cytotoxic drugs using CDA. Peripheral blood mononuclear cells (PBMC) as well as cell lines derived from FA patients were treated with two DNA interstrand crosslinking (ICL) agents, mitomycin C and cyclophosphamide. Our data indicate that the CDA detects hypersensitivity of cells from FA patients to mitomycin C. Further, cell lines derived from FA-patients were also hypersensitive to mitomycin C as well as cyclophosphamide, when assayed by the CDA. This study suggests that the CDA is a useful alternative for the diagnosis of FA patients' hypersensitivity to ICL agents.
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| 43. |
- Hijazi, Ziad
(författare)
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New Risk Markers in Atrial Fibrillation
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value.The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months.Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both cardiac biomarkers simultaneously the risk stratification improved even further for all outcomes.In conclusion the analyses for the first time display that elevation of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke, cardiovascular events and mortality. Persistent elevation of troponin and NT-proBNP indicate a worse prognosis than transient elevations or no elevations of either marker. The cardiac biomarkers added substantial improvements to existing risk stratification models.
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| 44. |
- Holmström, Alexandra, et al.
(författare)
-
An integrated multiple marker modality is superior to NT-proBNP alone in prognostic prediction in all-cause mortality in a prospective cohort of elderly heart failure patients
- 2013
-
Ingår i: European Geriatric Medicine. - : Elsevier BV. - 1878-7649. ; 4:6, s. 365-371
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying the individual mortality risk for elderly heart failure (HF) patients is challenging because of heterogeneity, comorbidity and higher age. To overcome this, an integrated multiple marker modality has been proposed for better prognostic prediction than a single variable, this has not been evaluated. Aim: The aim of this study is to identify whether a multiple marker modality is better than N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone for all-cause mortality in elderly HF patients. Methods: A prospective cohort of 361 patients (65 +/- 15 years) referred for echocardiography because of suspected HF was studied, among them, 179 had HF (71 +/- 13). In this cohort blood sampling, electrocardiogram and clinical examinations were performed within approximately 24 hours after the echocardiography. To assess prognostic value of multiple marker modality for all-cause mortality, patients were followed up for 24 +/- 7 months. Results: In the three multivariate analyses, NT-proBNP, cystatin C, red blood cell distribution width (RDW), midregional pro-atrial natriuretic peptide (MR-proANP), pulmonary artery pressure, estimated glomerular filtration rate (eGFR) less than 60 mL/min, anemia, diuretics and sinus rhythm are prognostic predictors of all-cause mortality in elderly HF patients. When analyzing all these variables in one multivariate analysis, only NT-proBNP, eGFR less than 60 mL/min, anemia and diuretics are prognostic predictors of all-cause mortality in elderly HF patients. Two different multiple marker models incorporating NT-proBNP, clinical and laboratory variables were created. The sensitivity and specificity of the two different multiple marker modalities are higher than for NT-proBNP alone. The risk score based on multivariate analysis Wald X-2 values is preferred considering its simplicity and feasibility in daily clinical practice. Conclusion: A multiple marker modality was proven to improve prognostic prediction in elderly HF patients compared to NT-proBNP alone. (C) 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
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| 45. |
- Holmström, Alexandra, et al.
(författare)
-
Levels of copeptin among elderly patients in relation to systolic heart failure and heart failure with normal ejection fraction
- 2013
-
Ingår i: European Geriatric Medicine. - : Elsevier BV. - 1878-7649. ; 4:3, s. 139-144
-
Tidskriftsartikel (refereegranskat)abstract
- Background: High copeptin levels are linked to a poor prognosis in heart failure (HF). Studies of copeptin levels in elderly HF patients with normal left ventricular ejection fraction (HFNEF) have reported conflicting results. Aim: The aim is to study the relationship between copeptin levels and HF in the elderly. Methods: In a prospective cohort of 261 patients with a mean age of 70 +/- 11 years, referred for echocardiography due to suspected HF. Electrocardiography, blood sampling and clinical examination were performed within approximately 24 hours after echocardiography. The study group was categorised according to the following definitions: systolic HF (SHF) (39%), HFNEF (previously called diastolic HF) (19%), uncertain HFNEF (19%), where only symptoms and partial echocardiography signs supported the diagnosis and a group in which HF was excluded (Non-HF) (23%). Results: Copeptin levels were higher in patients with SHF and HFNEF compared with non-HF patients. Patients with uncertain HFNEF had similar copeptin levels as the non-HF group. Copeptin across quartiles was related to an increased proportion of SHF, low ejection fraction (LVEF), high pulmonary artery pressure (PA) (all P < 0.01), signs of increased preload (LVDD) (P < 0.05), and higher levels of a panel of biomarkers (P < 0.01), but not to the incidence of HFNEF. In a stepwise multiple linear regression analysis there was a positive relationship between copeptin and cystatin C, high-sensitivity troponin T (both P < 0.001) and male gender (P < 0.05). Conclusion: Copeptin levels are elevated in both SHF and HFNEF in the elderly but not in patients in whom the HFNEF diagnosis is based only on symptoms and partial echocardiography findings.
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| 46. |
- Holmström, Alexandra, et al.
(författare)
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Red blood cell distribution width and its relation to cardiac function and biomarkers in a prospective hospital cohort referred for echocardiography
- 2012
-
Ingår i: European Journal of Internal Medicine. - : Elsevier BV. - 0953-6205. ; 23:7, s. 604-609
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Tidskriftsartikel (refereegranskat)abstract
- Background: Red blood cell distribution width (RDW), a measure of anisocytosis, is a prognostic biomarker for heart failure (HF). However it is still unclear how RDW is associated with heart function and established cardiac biomarkers. Methods and results: In a prospective hospital cohort of 296 patients referred for echocardiography because of suspected HF, blood sampling and clinical examination were performed within 24 h after echocardiography. The patients were divided into four HF groups, including one group where the HF diagnosis was uncertain (gray zone). In the patients the mean age was 70 +/- 11 years, 44% with systolic HF (SHF), 18% with heart failure with normal ejection fraction (HFNEF), 17% with gray zone and 21% without HF (non-HF). RDW was higher among patients with SHF and HFNEF, compared with gray zone and non-HF patients. The distribution of different variables over the RDW quartiles showed an inverse correlation between RDW levels and LVEF and a positive correlation between RDW and NT-proBNP levels. Further analysis with stepwise multiple linear regression demonstrated that NT-proBNP levels, but not LVEF, were independently correlated with RDW. Conclusion: In patients referred for echocardiography because of suspected HF, RDW levels were higher in patients with SHF and HFNEF. Moreover, NT-proBNP levels were independently linked with elevated RDW. (C) 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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| 47. |
- Isaksson, Helena, 1978-
(författare)
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Clinical studies of RNA as a prognostic and diagnostic marker for disease
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Technologies for RNA detection are evolving rapidly and gives an op-portunity for discovery of new markers for early detection of complex diseases. Today in clinical work we rely on signs and symptoms in com-bination with the measurement of protein levels for diagnosis. The quick turnaround time of mRNA synthesis may provide an earlier diagnostic signal than protein-based biomarkers assays, in acute dramatic condi-tions such as acute mesenteric ischemia (AMI), for early detection of cancer, as prognostic tool in cancer treatment and as an aid in difficult diagnosis of unknown origin.The main goals of this thesis was to apply a whole genome approach to study different complex diseases to evaluate the applicability of RNA as a diagnostic or prognostic marker for disease, preferably from an easily accessible source such as peripheral blood. This was investigated in an animal model with induced AMI, a cohort of ovarian cancer patients and in a single-patient study of a girl with a severe inflammatory syn-drome.Through this thesis we have gained insight into how gene expression is regulated in ischemic intestinal tissue.We found that a peripheral blood test can distinguish between ovarian cancer patients with or without residual tumour mass after surgery with the help of expression analysis of six genes. We also found that gene expressions of three genes can predict overall survival in peripheral whole blood from ovarian cancer patients. And that gene expression profiles indeed can significantly distinguish between two groups of high and low risk ovarian cancer. In the single-patient study, we tried but failed to device a successful treatment before it was too late. Neverthe-less, the things we learned and the case studies that were published may serve as a diagnostic tool for clinicians facing similar syndromes.
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| 48. |
- Ismail, Ismail Hassan, 1975, et al.
(författare)
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Activation of ataxia telangiectasia mutated by DNA strand break-inducing agents correlates closely with the number of DNA double strand breaks.
- 2005
-
Ingår i: The Journal of biological chemistry. - 0021-9258. ; 280:6, s. 4649-55
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Tidskriftsartikel (refereegranskat)abstract
- The protein kinase ataxia telangiectasia mutated (ATM) is activated when cells are exposed to ionizing radiation (IR). It has been assumed that ATM is specifically activated by the few induced DNA double strand breaks (DSBs), although little direct evidence for this assumption has been presented. DSBs constitute only a few percent of the IR-induced DNA damage, whereas the more frequent single strand DNA breaks (SSBs) and base damage account for over 98% of the overall DNA damage. It is therefore unclear whether DSBs are the only IR-induced DNA lesions that activate ATM. To test directly whether or not DSBs are responsible for ATM activation, we exposed cells to drugs and radiation that produce different numbers of DSBs and SSBs. We determined the resulting ATM activation by measuring the amount of phosphorylated Chk2 and the numbers of SSBs and DSBs in the same cells after short incubation periods. We found a strong correlation between the number of DSBs and ATM activation but no correlation with the number of SSBs. In fact, hydrogen peroxide, which, similar to IR, induces DNA damage through hydroxyl radicals but fails to induce DSBs, did not activate ATM. In contrast, we found that calicheamicin-induced strand breaks activated ATM more efficiently than IR and that ATM activation correlated with the relative DSB induction by these agents. Our data indicate that ATM is specifically activated by IR-induced DSBs, with little or no contribution from SSBs and other types of DNA damage. These findings have implications for how ATM might recognize DSBs in cells.
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| 49. |
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| 50. |
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