Publications

No abstract is provided for this article.

Background Vessel angulation and large changes in vessel geometry after stent implantation have been associated with an increased risk of target lesion failure (TLF) using bare-metal stents. Second-generation drug-eluting stents (DES)offer superior conformability and inhibition of neointima. The aim of the study is to investigate the relationship between pre and post-implant vessel geometry and the occurrence of TLF at 1 year after treatment with second-generation DES; and to compare the conformability of Resolute and Xience stents. Methods The RESOLUTE All-Comers trial randomized 2292 patients (3366 lesions) to Resolute zotarolimus-DES (Medtronic CardioVascular) or Xience everolimus-DES (Abbott Vascular). At 1 year, 176 lesions (121 patients)presented with TLF; a composite of cardiac death, acute myocardial infarction (AMI) and target lesion revascularization (TLR). Lesions with TLF were matched with 176 lesions (168 patients) without TLF adjusting for clinical and procedural characteristics. The number of bends, vessel curvature and angulation were assessed with quantitative coronary angiography pre and post-implantation. The absolute difference post minus pre-implantation was used as a surrogate of stent conformability. Results At pre-implantation, lesions without and with TLF had similar numbers of bends/lesion (1.81 vs 1.74; P = .35), vessel curvature (0.295 cm−1 vs 0.363 cm−1; P = .13) and vessel angulation (46.3° vs 43.5°; P = .80), respectively. Lesions without and with TLR also had similar numbers of bends/lesion (1.39 vs 1.39; P = .83), vessel curvature (0.368 cm−1 vs 0.325 cm−1; P = .33) and angulation (40.2° vs 37.2°; P = .19). Lesions without and with in-hospital AMI also presented with similar number of bends/lesion (1.69 vs 1.81; P = .48), vessel curvature (0.349 cm−1 vs 0.345 cm−1; P = .91) and vessel angulation (43.53° vs 48.45°; P = .38). The absolute difference post- − pre-implantation was similar in lesions without and with TLF, TLR and In-hospital AMI. The absolute difference post- − pre-implantation was similar with both Resolute and Xience in vessel curvature (−0.046 cm−1 vs −0.047 cm−1; P = .66) and was smaller in number of bends/lesion (−0.08 vs −0.16; P = .13) and in vessel angulation (−6.0° vs −10.1°; P = .03) with the Resolute. Conclusions Bended, curved, and angulated lesions and changes in the number of bends/lesion, vessel curvature, and angulation from pre to post-implantation have no relation with TLF and TLR at 1 year and have no relation with In-hospital AMI using second-generation of DES. Resolute appears to be more conformable than Xience.

Comparison of magnetic guidewire navigation in percutaneous coronary intervention (magnetic PCI) across distal and/or complex lesions versus conventional navigation (conventional PCI).Forty-seven consecutive patients (age 61 +/- 10 yr) undergoing elective single vessel magnetic PCI for distal and/or complex lesions were matched by age and lesion location with 45 patients undergoing conventional PCI (age 63 +/- 10 yr). Technical success rate was defined as an intraluminal wire position distal to the stenosis. Procedural outcome and costs were evaluated. Baseline demographics and angiographic characteristics of the two groups were similar. The technical success rate did not differ between magnetic and conventional PCI (95.7 vs 97.8%; p = 1.00). Significantly shorter procedural and fluoroscopy time were observed for magnetic compared to conventional PCI (29.9 +/- 17.6 vs 41.1 +/- 21 min, p = 0.007; 7.5 +/- 7.3 vs 16.1 +/- 22.4 min, p = 0.02 respectively). Less contrast was used in the magnetic PCI group (58 ml/patient; P = 0.02). These advantages resulted in a mean estimated saving of 1400 euro per patient (P < 0.001). Advantages of procedural outcome were even more pronounced in the ACC/AHA lesion class C subgroup.Magnetic compared to conventional PCI is an attractive novel technique that proved to be feasible and safe and might be faster in distal and especially complex lesions.

No abstract is provided for this article.

Platelet-activating factor (PAF) administered i.v. or by aerosol to guinea pigs elicited an increase in airway responsiveness to both acetylcholine and histamine when compared with guinea pigs exposed to the vehicle bovine serum albumin (BSA). After i.v. PAF, the ED100 for acetylcholine and histamine was 5.4 and 3.4 tig/kg, respectively, in comparison with 17 and 6 µg/kg, respectively, before PAF, representing approximately a 3- and 2-fold increase in responsiveness, respectively. After aerosol PAF (500 µg), the ED100 for acetylcholine and histamine was 13 and 7 µg/kg, respectively, whereas after aerosolized BSA, the ED100 for acetylcholine and histamine was 23 and 12 µg/kg, respectively, representing approximately a 2-fold increase in responsiveness. However, airway smooth muscle obtained from these PAF- or BSA-treated animals did not exhibit any differences in contractile response to histamine or acetylcholine in vitro. Likewise, there were no significant differences in the binding affinity or receptor density between PAF- and BSA-treated tissues with [3H]quinuclidinylbenzilate or [3H]pyrilamine binding, which were used to identify muscarinic and H1-histamine receptors, respectively. Furthermore, histamine and carbachol-induced phosphoinositide hydrolysis was similar in PAF- and BSA-treated tracheal smooth muscle preparations. Thus, PAF induces airway hyperresponsiveness in the guinea pig that is not related to changes in airway smooth muscle or to changes in muscarinic and histamine (H1) receptor density or function.

Asthma is an inflammatory disease of the lungs and the transcription factor NF-kappa B regulates the production of numerous inflammatory mediators that may have a role in the pathogenesis of asthma. Hence, the signalling pathways leading to NF-kappa B activation are considered prime targets for novel anti-inflammatory therapies. The prevention of NF-kappa B activity in mice, through the knockout of IKK beta or p65, causes fatal liver degeneration in utero making it difficult to determine the full implications of inhibiting NF-kappaB activity in tissues physiologically relevant to human diseases. This study used adenovirus delivery of a dominant inhibitor of NF-kappaB (I kappa B alpha delta N) and dominant-negative IKK alpha (IKK alpha(KM)) and IKK beta (IKK beta(KA)) to investigate the role of the individual IKKs in NF-kappa B activation and inflammatory gene transcription by human pulmonary A549 cells. Overexpression of IKK beta(KA) or I kappa B alpha delta N prevented NF-kappa B-dependent transcription and DNA binding. IKK beta(KA) also prevented I kappa B alpha kinase activity. Similarly, IKK beta(KA) and I kappa B alpha delta N overexpression also inhibited IL-1beta- and TNF alpha-dependent increases in ICAM-1, IL-8 and GM-CSF in addition to IL-1beta-mediated increases in cyclooxygenase-2 expression, whereas IKK alpha(KM) overexpression had little effect on these outputs. IKK beta(KA) also reduced cell viability and induced caspase-3 and PARP cleavage regardless of the stimuli, indicating the induction of apoptosis. This effect seemed to be directly related to IKK beta kinase activity since I kappa B alpha delta N only induced PARP cleavage in TNF alpha-treated cells. These results demonstrate that inhibition of IKK beta and NF-kappa B suppresses inflammatory mediator production and reduces A549 cell viability. Thus, novel therapies that target IKK beta could have potent anti-inflammatory effects and may be beneficial in the treatment of certain cancers.

Objectives The aim of the study was to investigate 4-year outcomes and predictors of repeat revascularization in patients treated with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Minneapolis, Minnesota) and XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) in the RESOLUTE (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) All-Comers trial. Background Data on long-term outcomes of new-generation drug-eluting stents are limited, and predictors of repeat revascularization due to restenosis and/or progression of disease are largely unknown. Methods Patients were randomly assigned to treatment with the R-ZES (n = 1,140) or the EES (n = 1,152). We assessed pre-specified safety and efficacy outcomes at 4 years including target lesion failure and stent thrombosis. Predictors of revascularization at 4 years were identified by Cox regression analysis. Results At 4 years, the rates of target lesion failure (15.2% vs. 14.6%, p = 0.68), cardiac death (5.4% vs. 4.7%, p = 0.44), and target vessel myocardial infarction (5.3% vs. 5.4%, p = 1.00), clinically-indicated target lesion revascularization (TLR) (7.0% vs. 6.5%, p = 0.62), and definite/probable stent thrombosis (2.3% vs. 1.6%, p = 0.23) were similar with the R-ZES and EES. Independent predictors of TLR were age, insulin-treated diabetes, SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score, treatment of saphenous vein grafts, ostial lesions, and in-stent restenosis. Independent predictors of any revascularization were age, diabetes, previous percutaneous coronary intervention, absence of ST-segment elevation myocardial infarction, smaller reference vessel diameter, SYNTAX score, and treatment of left anterior descending, right coronary artery, saphenous vein grafts, ostial lesions, or in-stent restenosis. Conclusions R-ZES and EES demonstrated similar safety and efficacy throughout 4 years. TLR represented less than one-half of all repeat revascularization procedures. Patient- and lesion-related factors predicting the risk of TLR and any revascularization showed considerable overlap. (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention [RESOLUTE-AC]; NCT00617084)