| 1. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2014
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Lindblom, P, et al.
(författare)
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Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies
- 2012
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Ingår i: Toxicologic pathology. - : SAGE Publications. - 1533-1601 .- 0192-6233. ; 40:1, s. 18-32
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Tidskriftsartikel (refereegranskat)abstract
- Tesaglitazar was developed as a dual peroxisome proliferator–activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.
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| 7. |
- Bahit, M C, et al.
(författare)
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Heart failure complicating non-ST-segment elevation acute coronary syndrome: timing, predictors, and clinical outcomes
- 2013
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1779 .- 2213-1787. ; 1:3, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study sought to describe the occurrence and timing of heart failure (HF), associated clinical factors, and 30-day outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Little is known about HF-complicating NSTE-ACS. METHODS: Using pooled patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF, associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression models to identify clinical factors associated with HF at presentation and to determine the association between HF and 30-day mortality. RESULTS: Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization. A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during hospitalization were older, more often female, and had a higher risk of death at 30 days than patients without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly associated with HF during hospitalization. CONCLUSIONS: In this large cohort of NSTE-ACS patients, presenting with or developing HF during hospitalization was associated with an increased risk of 30-day mortality. Research targeting new strategies to prevent and manage HF in this high-risk population is needed.
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