| 1. |
- Van Den Bossche, Maarten J., et al.
(author)
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Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders
- 2012
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In: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 159B:4, s. 465-475
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Journal article (peer-reviewed)abstract
- The GWAS-based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage-dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient-control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7?kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 1726 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.
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| 2. |
- Brugaletta, Salvatore, et al.
(author)
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Morphology of coronary artery lesions assessed by virtual histology intravascular ultrasound tissue characterization and fractional flow reserve
- 2012
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In: The International Journal of Cardiovascular Imaging. - : Springer Science and Business Media LLC. - 1569-5794 .- 1875-8312 .- 1573-0743. ; 28:2, s. 221-228
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Journal article (peer-reviewed)abstract
- Fractional flow reserve (FFR) is an index of the physiological significance of a coronary stenosis. Patients who have lesions with a FFR of >0.80, even optimally treated with medication, have however a MACE rate ranging from 8 to 21%. Coronary plaques at high risk of rupture and clinical events can be also identified by virtual histology intravascular ultrasound (IVUS-VH) as plaques with high amount of necrotic core (NC) abutting the lumen. Aim of this exploratory study was to investigate whether the geometry and composition of lesions with FFR ≤ 0.80 were different from their counterparts. Fifty-five consecutive patients in whom FFR was clinically indicated on a moderate angiographic lesion, received also an imaging investigation on the same lesion with IVUS-VH. Data on plaque geometry and composition was analyzed. Patients were subdivided in two groups according to the value of FFR (> or ≤0.80). Lesions with a FFR ≤ 0.80 (n = 17) showed a slightly larger plaque burden than those with FFR > 0.80 (n = 38) (54.6 ± 0.7% vs. 51.7 ± 0.7% P = 0.1). In addition, they tend to have less content of necrotic core than their counterparts (14.2 ± 8% vs. 19.2 ± 10.2%, P = 0.08). No difference was found in the distribution of NC-rich plaques (fibroatheroma and thin-capped fibroatheroma) between groups (82% in FFR ≤ 0.80 vs. 79% in FFR > 0.80, P = 0.5). Although FFR ≤ 0.80 lesions have larger plaque size, they do not differ in composition from the ones with FFR > 0.80. Further exploration in a large prospective study is needed to study whether the lesions with FFR > 0.80 that are NC rich are the ones associated with the presence of clinical events at follow-up.
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| 3. |
- De Bruyne, Bernard, et al.
(author)
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Fractional Flow Reserve-Guided PCI for Stable Coronary Artery Disease
- 2014
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In: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 371:13, s. 1208-1217
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Journal article (peer-reviewed)abstract
- BACKGROUND: We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.METHODS: In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.RESULTS: The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P = 0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P = 0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.CONCLUSIONS: In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone.
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| 4. |
- Hamilos, Michalis, et al.
(author)
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Relationship between peripheral arterial reactive hyperemia and residual platelet reactivity after 600 mg clopidogrel
- 2011
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 32:1, s. 64-71
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Journal article (peer-reviewed)abstract
- Clopidogrel reduces long-term ischemic events in patients with acute coronary syndrome or stable angina (SA) undergoing percutaneous coronary intervention (PCI). Endothelial function improvement has been proposed, among other factors, for this beneficial effect of clopidogrel, but whether this might be associated to its anti-platelet action remains unclear. We tested the hypothesis that clopidogrel improvement of peripheral vascular endothelial function might be associated with inhibition of platelet aggregation. Endothelial function was evaluated before and at least 12 h after 600 mg clopidogrel in 43 SA pts undergoing elective PCI by: (a) reactive hyperemia peripheral arterial tonometry (measuring the Endoscore); (b) circulating endothelial microparticles (EMPs). Response to clopidogrel was measured with point-of-care VerifyNow P2Y12 assay and expressed as platelet reaction unit (PRU) and percent platelet inhibition (%PI). High platelet reactivity after clopidogrel was defined as PRU ≥ 240. Endothelial function improved after clopidogrel in 20 pts. Changes in Endoscore (Δ Endoscore) were significantly correlated with both PRU (r = -0.61, P < 0.001) and %PI (r = 0.57, P < 0.001). Endoscore significantly increased after clopidogrel in pts with PRU < 240 (0.38 ± 0.26 to 0.57 ± 0.33, P < 0.001), but did not in pts with PRU ≥ 240 (0.53 ± 0.31 to 0.40 ± 0.37, P = 0.12). EMPs were also significantly reduced in pts with PRU < 240 (222 [140-593] to 142 [83-371]/μl, P = 0.001), while no changes were observed in pts with PRU ≥ 240 (256 [178-531] to 388 [238-499]/μl, P = 0.55). In patients with stable coronary artery disease, a single 600 mg clopidogrel loading dose improves vascular endothelial function. This improvement is associated with optimal platelet inhibition and it is not observed in patients with post-clopidogrel high platelet reactivity.
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