| 1. |
- Forsberg, Anton, et al.
(författare)
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Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer-Verlag New York. - 1619-7070 .- 1619-7089. ; 40:4, s. 580-593
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.RESULTS: AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.CONCLUSION: Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.
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| 2. |
- Hellström Ängerud, Karin, et al.
(författare)
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Differences in symptoms, first medical contact and pre-hospital delay times between patients with ST- and non-ST-elevation myocardial infarction
- 2019
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Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:3, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Aim: In ST-elevation myocardial infarction, time to reperfusion is crucial for the prognosis. Symptom presentation in myocardial infarction influences pre-hospital delay times but studies about differences in symptoms between patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction are sparse and inconclusive. The aim was to compare symptoms, first medical contact and pre-hospital delay times in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction.Methods and results: This multicentre, observational study included 694 myocardial infarction patients from five hospitals. The patients filled in a questionnaire about their pre-hospital experiences within 24 h of hospital admittance. Chest pain was the most common symptom in ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (88.7 vs 87.0%, p=0.56). Patients with cold sweat (odds ratio 3.61, 95% confidence interval 2.29–5.70), jaw pain (odds ratio 2.41, 95% confidence interval 1.04–5.58), and nausea (odds ratio 1.70, 95% confidence interval 1.01–2.87) were more likely to present with ST-elevation myocardial infarction, whereas the opposite was true for symptoms that come and go (odds ratio 0.58, 95% confidence interval 0.38-0.90) or anxiety (odds ratio 0.52, 95% confidence interval 0.29–0.92). Use of emergency medical services was higher among patients admitted with ST-elevation myocardial infarction. The pre-hospital delay time from symptom onset to first medical contact was significantly longer in non-ST-elevation myocardial infarction (2:05 h vs 1:10 h, p=0.001).Conclusion: Patients with ST-elevation myocardial infarction differed from those with non-ST-elevation myocardial infarction regarding symptom presentation, ambulance utilisation and pre-hospital delay times. This knowledge is important to be aware of for all healthcare personnel and the general public especially in order to recognise symptoms suggestive of ST-elevation myocardial infarction and when to decide if there is a need for an ambulance.
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| 3. |
- Isaksson, Rose-Marie, 1964-, et al.
(författare)
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Geographical Diversities in Symptoms, Actions and Prehospital Delay Times in Swedish ST-Elevation Myocardial Infarction(STEMI) Patients : A Descriptive Multicenter Cross-Sectional Survey Study
- 2019
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Ingår i: Insights of Cardiology Open Access. - : GRF Publishers.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Geographical variations in cardiovascular mortality have been reported in Sweden as well as in other countries. Little attention has been given to possible variations in symptoms, actions and pre-hospital delay times in ST-elevation myocardial infarction (STEMI) patients, as a reason for this diversity. We aimed to study whether STEMI patients from the northern and southern parts of Sweden differ in symptoms and actions that may affect the pre-hospital delay times.Methods: SymTime was a multicentre cross-sectional survey study where STEMI patients admitted to the coronary care unit completed a validated questionnaire within 24 hours after admission. In total, 531 patients were included, 357 in the southern and 174 in the northern part of Sweden.Results: There were no significant differences in age. However, patients in the north had more often hypertension (52 vs 42%, p=0.02) or other concomitant comorbidities (24 vs 14%, p=0.01). Patients in the south experienced more anxiety (14 vs. 7%, p=0.01) and fear (23 vs. 14%, p=0.02) and more often contacted the emergency medical services (EMS) as first medical contact (FMC) (54 vs 44%, p=0.05). There were no differences in other main or associated symptoms or in pre-hospital delay times. Conclusions: Patients with STEMI in the southern vs. the northern part of Sweden had more anxiety and fear, despite that they were less often alone at onset of symptoms. There were no differences in pre-hospital delay times. Although patients from the southern region contacted EMS as their FMC more frequently, it is still worrying that too few patients utilize the EMS.
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| 4. |
- Sederholm Lawesson, Sofia, et al.
(författare)
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Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.
- 2023
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 329:5, s. 393-404
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Tidskriftsartikel (refereegranskat)abstract
- Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100.A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
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| 5. |
- Sederholm Lawesson, Sofia, 1973-, et al.
(författare)
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Gender differences in symptom presentation of ST-elevation myocardial infarction : an observational multicenter survey study
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 264, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Symptom presentation has been sparsely studied from a gender perspective restricting the inclusion to ST elevation myocardial infarction (STEMI) patients. Correct symptom recognition is vital in order to promptly seek care in STEMI where fast reperfusion therapy is of utmost importance. Female gender has been found associated with atypical presentation in studies on mixed MI populations but it is unclear whether this is valid also in STEMI.OBJECTIVES: We assessed whether there are gender differences in symptoms and interpretation of these in STEMI, and if this is attributable to sociodemographic and clinical factors.METHODS: SymTime was a multicenter observational study including a validated questionnaire and data from medical records. Eligible STEMI patients (n = 532) were enrolled within 24 h after admittance at five Swedish hospitals.RESULTS: Women were older, more often single and had lower educational level. Chest pain was less prevalent in women (74 vs 93%, p < 0.001), whereas shoulder (33 vs 15%, p < 0.001), throat/neck (34 vs 18%, p < 0.001), back pain (29 versus 12%, p < 0.001) and nausea (49 vs 29%, p < 0.001) were more prevalent. Women less often interpreted their symptoms as of cardiac origin (60 vs 69%, p = 0.04). Female gender was the strongest independent predictor of non-chest pain presentation, odds ratio 5.29, 95% confidence interval 2.85-9.80.CONCLUSIONS: A striking gender difference in STEMI symptoms was found. As women significantly misinterpreted their symptoms more often, it is vital when informing about MI to the society or to high risk individuals, to highlight also other symptoms than just chest pain.
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| 6. |
- Sorbe, Bengt, et al.
(författare)
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A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation
- 2012
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Ingår i: International Journal of Oncology. - Athens : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 40:3, s. 773-781
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to assess the response rate, toxicity, progression-free survival (PFS) and overall survival (OS) in a series of advanced stage ovarian carcinoma patients treated with a first-line weekly docetaxel and three weekly carboplatin regimens. All eligible patients were treated with intravenous docetaxel (30 mg/m(2)) on Days 1, 8 and 15, and carboplatin (area under the curve, 5) on Day 1; Q21 days for at least 6 cycles. Neurological tests, questionnaires, and the EORTC QLQ-C30 and OV28 were used for quality-of-life assessments. One hundred and six patients received at least one cycle of primary chemotherapy (median 6.0; range, 1-9) and they were evaluable for toxicity assessment. Eighty-five patients had evaluable disease and received at least 3 courses of chemotherapy and were evaluable for clinical response rate. The overall response rate was 78.8% (95% CI 70.1-87.5%) and the biochemical response was 92.8% (95% CI 87.2-98.4%). The median PFS was 12.0 months and the median OS was 35.3 months. Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3 or 4 thrombocytopenia. No patients experienced grade 3-4 sensory neuropathy. Epiphora, nail changes and fatigue were frequently recorded non-hematological side effects. The tolerable hematological toxicity (no need for colony-stimulating factors) and the low rate of severe neurotoxicity (only grade 1-2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgery make this regimen an interesting alternative in selected patients.
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| 7. |
- Sorbe, Bengt, et al.
(författare)
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Phase II Study of Docetaxel Weekly in Combination With Carboplatin Every 3 Weeks as First-Line Chemotherapy in Stage IIB to Stage IV Epithelial Ovarian Cancer
- 2012
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Ingår i: International Journal of Gynecological Cancer. - : Lippincott, Williams and Wilkins / Wiley-Blackwell. - 1048-891X .- 1525-1438. ; 22:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to assess the response rate, toxicity, progression-free survival, and overall survival in a series of patients with advanced-stage ovarian carcinoma treated with a first-line weekly docetaxel and 3 weekly carboplatin regimen. less thanbrgreater than less thanbrgreater thanMethods: All eligible patients were treated with intravenous docetaxel (30 mg/m(2)) on days 1, 8, and 15, and carboplatin (area under the curve, 5) on day 1; every 21 days for at least 6 cycles. less thanbrgreater than less thanbrgreater thanResults: One hundred six patients received at least one cycle of primary chemotherapy (median, 6.0; range, 1-9), and they were evaluable for toxicity assessment. Eighty-five patients had evaluable (measurable) disease and received at least 3 courses of chemotherapy and were evaluable for clinical response rate. The overall response rate was 78.8% (95% confidence interval, 70.1%-87.5%), and the biochemical response 92.8% (95% confidence interval, 87.2%-98.4%). The median progression-free survival was 12.0 months and the median overall survival was 35.3 months. Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3 or 4 thrombocytopenia. No patients experienced grade 3 to grade 4 sensory neuropathy. Epiphora, nail changes, and fatigue were frequently recorded nonhematologic adverse effects. less thanbrgreater than less thanbrgreater thanConclusions: The tolerable hematologic toxicity (no need for colony-stimulating factors) and the low rate of neurotoxicity (only grades 1-2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgerymake this regimen an interesting alternative in selected patients.
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| 8. |
- Swahn, Britt-Marie
(författare)
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Synthesis and structure activity relationships of competitive NMDA antagonists with analgesic activity
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The compounds cis-3-(1-oxo-2-phosphonoethyl)-2-piperidinecarboxylic acid 1 and cis-3-(1-hydroxy-2-phosphonoethyl)-2-piperidinecarboxylic acid 2 were synthesized and found to be potent N-methyl-D-aspartate (NMDA) antagonists. NMR analysis showed that 1 prefers a 2eq,3ax chair conformation probably due to a conformer-stabilizing internal hydrogen bond. The active enantiomers (2R,3S)-3-(l-oxo-2-phosphonoethyl)-2-piperidinecarboxylic acid and (2R,3S,1'R)-3-(l-hydroxy-2-phosphonoethyl)-2-piperidinecarboxylic acid were synthesized and the NMDA receptor binding affinities (Ki values) were 64 and 74 nM, respectively.The analgesic effects of 1 and 2 were evaluated using the mouse hot-plate test and the mouse formalin model.A series of substituted (R)-α-amino-3-(phosphonomethyl)-2-quinolinepropanoic acids were synthesized. The active enantiomers were synthesized via a palladium-catalyzed coupling reaction of a 2-bromoquinoline derivative and a zinc reagent made from protected β-iodo-(R)-alanine. (R)-α-Amino-6,7-dimethyl-3-(phosphonomethyl)-2-quinolinepropanoic acid 3 exhibited a Ki value of 5 nM. A NiCl2(dppp)2-catalyzed coupling reaction with the zinc reagent made from [14C]-methyl iodide was used in the synthesis of radiolabeled 3.(R)-α-amino-3-(phosphonomethyl)-1,8-naphthyridine-2-propanoic acid, (R)-α-amino-3-(phosphonomethyl)-1,6-naphthyridine-2-propanoic acid and α-amino-3-(phosphonomethyl)-2-naphthalenepropanoic acid were synthesized. The structure activity relationships of the aryl- and heteroaryl-spaced NMDA antagonists revealed high receptor affinity for lipophilic substituents.
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