Cobalt-chrome MULTI-LINK VISION-stent implantation in diabetics and complex lesions: results from the DaVinci-Registry.

AIMS: Restenosis in bare-metal stents is in part related to stent design and material. Optimized strut design of cobalt-chrome (CoCr) stents may yield nearly comparable results to drug-eluting stents (DES) in selected lesions. The prospective multicenter DaVinci registry investigates the clinical outcome of a CoCr coronary stent (MULTI-LINK VISION), particularly in terms of patients with diabetes and complex lesions (B1, B2, C). METHODS AND RESULTS: The prospective internet-based registry included 1,344 patients (76% males, aged 66 +/- 10 years) undergoing stent implantation (n = 1,642) in 32 centres from July 2003 to June 2004. Follow-up data (median 9 +/- 1 months) of this cohort were available for 1,289 patients (98.1%). Of these patients 327 (26.2%) were diabetics. In total, 1,429 de-novo lesions (A 11.9%, B1 47.7%, B2 31.6%, C 8.8%) were treated with the CoCr stent. The predefined primary endpoint was defined as a composite of death, Q-wave myocardial infarction (STEMI), non-STEMI (NSTEMI), target vessel revascularization (TVR) by coronary bypass graft (CABG) or PCI at 270 days (target vessel failure, TVF). Secondary endpoints include death, time to the first myocardial infarction, TVR and CABG. The cumulative incidence of major adverse cardiac events (MACE) was 12.4% with 0.8% deaths, 1.5% non-fatal MI, and 9.7% TVR. TVF in the overall cohort was documented in 137 (10.8%) patients. For diabetics and complex lesions TVF was 13.8% (95% CI 4.2-18) and 11.4% (95% CI 2.0-13.3), respectively. CONCLUSION: This large registry confirms good acute and long-term success of CoCr stents making this strategy valuable, particularly in a special cohort (diabetics and complex lesions) as long as late stent thrombosis with DES plays a role and short-term antiplatelet therapy is favoured.

Inhibition by fibrates of plasminogen activator inhibitor type-1 expression in human adipocytes and preadipocytes.

Plasminogen activator inhibitor type-1 (PAI-1), an established marker and mediator of cardiovascular risk, is produced extensively in adipose tissue. Fibrates are hypolipidemic peroxisome proliferator activated receptor-alpha (PPARalpha) agonists. Recent laboratory and clinical observations indicate that they are also anti-atherosclerotic. Mechanisms responsible, however, remain to be fully understood. The present study was designed to elucidate modulation of PAI-1 expression in adipose cells by fibrates as a potential mechanism. Expression of PPARalpha was verified by PCR, immunohistochemistry, and Western blotting. In cultured preadipocytes and adipocytes gemfibrozil and fenofibrate significantly reduced PAI-1 protein expression by up to 55 +/- 5% and 34 +/- 4% under basal conditions and up to 56 +/- 6% and 31 +/- 6% under conditions of stimulation of the cells with 40 pM transforming growth factor (TGF)beta, respectively. Quantification of mRNA showed that the gemfibrozil-induced effect was at least in part regulated at the transcriptional level. Incubations with non-fibrate PPARalpha agonists showed similar reductions in PAI-1 expression. The decrease in PAI-1 expression induced by gemfibrozil was inhibited by MK886, a PPARalpha inhibitor. Furthermore, preadipocytes isolated from PPARalpha-deficient mice produced significantly more PAI-1 than those from wild-type mice upon stimulation with TGFbeta. Finally, fenofibrate reduced PAI-1 expression both in plasma and adipose tissue of hyperlipidemic mice. Our data support the view that PPARalpha activation down-regulates PAI-expression in adipose cells that may contribute in part to the reduction in cardiovascular mortality seen with fibrates in clinical trials.

[Striking a new path in medical education. CAMPUS, an interactive, case-based training system]. / Neue Wege in der kardiologischen Aus- und Weiterbildung: Erste Erfahrungen mit CAMPUS, einem interaktiven, fallbasierten Lernprogramm.

BACKGROUND AND PURPOSE: Computer-assisted teaching and learning tools offer new opportunities for improving education and training of medical professionals. CAMPUS represents a software for computer-based, problem-oriented learning. It is a case-based training system which provides the patient's history within a highly realistic, multimedia format. Thus, the interactive design is expected to challenge, test and improve the medical knowledge and the diagnostic skills of the students. The objective of the present study was to introduce CAMPUS as a computer-based learning tool and to present preliminary results with regard to acceptance and user-friendliness. METHODS: CAMPUS was evaluated by 52 students regarding quality and experienced learning success. A tutorial was conducted within separate, small-numbered groups of students, each working on one learning case. The virtual case started with a summary of the patient's leading symptoms. The students independently took the patient history and carried out the physical examination. Then, they were asked to suggest differential diagnoses, refer the patient to appropriate diagnostic examinations and were encouraged to choose adequate therapeutic strategies. Subsequently, the quality of CAMPUS and the subjective learning success were evaluated with a standardized questionnaire. RESULTS: Nearly all students described the user interface as visually attractive (51/52) and clearly structured (52/52). In particular, the students found the use of videos to be advantageous. A marked learning success was described by most students (46/52) and all students considered learning with CAMPUS to be effective. CONCLUSION: CAMPUS offers an innovative training program to improve medical education and to enhance conventional teaching methods efficiently.

Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidinediones.

Adipose tissue produces substantial amounts of plasminogen activator inhibitor type-1 (PAI-1), an established cardiovascular risk factor. This study evaluated PAI-1 expression in human adipose tissue in response to thiazolidinediones, insulin sensitising drugs activating peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Troglitazone, rosiglitazone, and ciglitazone significantly reduced PAI-1 protein expression in human preadipocytes under basal conditions and after stimulation of the cells with TGF-beta. Pioglitazone had no effect. In human adipocytes all four thiazolidinediones significantly attenuated PAI-1 expression. Signalling appeared to be mediated via PPAR-gamma and effects reflected, at least in part, changes in transcription. Accordingly, patients with insulin resistance may benefit from treatment with thiazolidinediones with respect to diminution of PAI-1 expression in adipose tissue and consequent potential reduction of cardiovascular risk.

Independence of growth factor induced plasminogen activator inhibitor type-1 (PAI-1) expression from the 4G/5G polymorphism of the PAI-1 gene.

Increased PAI-1 expression has been implicated in accelerating atherogenesis. Increases under some conditions are modulated by growth factors. Genetic factors such as the 4G/5G polymorphism in the promoter of the PAI-1 gene play a role under certain circumstances. The present study was designed to delineate for the first time interactions between growth factors and the 4G/5G polymorphism with respect to PAI-1 expression in human arterial smooth muscle cells (HASMC). HASMC were genotyped and exposed to growth factors. PAI-1 gene and protein expression were induced consistently by TGF-beta (up to 4.0-fold), PDGF (2.1-fold), TNF-alpha (1.7-fold), and thrombin (2.3-fold). Results were similar regardless of which genotype (4G/4G [n=9], 4G/5G [n=13], and 5G/5G [n=7]) was present. The induction of increased PAI-1 expression in human arterial smooth muscle cells by growth factors implicated in accelerated atherogenesis is independent of the PAI-1 4G/5G polymorphism. Accordingly, modulation of PAI-1 expression is likely to be influenced predominantly by environmental factors acting on, rather than genetic factors intrinsic to the PAI-1 promoter.

Effects of different thrombolytic treatment regimen with abciximab and tirofiban on platelet aggregation and platelet-leukocyte interactions: a subgroup analysis from the GUSTO V and FASTER trials.

BACKGROUND: Due to considerably high rates of reocclusion under standard thrombolytic therapy GP IIb/IIIa inhibitors have been combined with thrombolytics to improve therapeutic outcomes. Potential reasons for arterial reocclusion may be increased platelet activation, interaction of platelets with other cell types such as leukocytes and inadequate drug dosing due to lack of ideal platelet monitoring. We compared combination therapy regimens consisting of GP IIb/IIIa inhibitors and thrombolytics with respect to platelet inhibition and platelet-leukocyte interactions. METHODS AND RESULTS: From the GUSTO V trial (standard rPA vs. reduced dose rPA and abciximab) and the FASTER trial (standard TNK-tPA vs. reduced dose TNK-tPA and tirofiban) 15 patients were monitored by platelet aggregometry, rapid platelet function assay (RPFA) and flow cytometry (FC). rPA alone (n = 5) caused initial increases in platelet aggregation. However, platelet aggregation was significantly (p < 0.05) and sufficiently (>80%) inhibited by abciximab/rPA (n = 5) and tirofiban/TNK-tPA (n = 5). The platelet inhibitory effect of tirofiban/TNK-tPA was more pronounced compared to abciximab/rPA with a significant difference after 2 h (p < 0.05). Tirofiban/TNK-tPA and abciximab/rPA caused decreases in platelet-leukocyte aggregates as well as in binding of specific antibodies to the platelet vitronectin receptor and P-selectin (p < 0.05, respect.). No differences among the treatment groups were seen with respect to antibody binding to MAC-1 and CD154/CD40 ligand. CONCLUSIONS: Taken together, GP IIb/IIIa inhibitors overcome the platelet activating effect of thrombolytics resulting in sufficient platelet inhibition. RPFA is a suitable monitoring tool to accurately assess platelet inhibition. Within the given combination treatment regimen tirofiban appears to be more effective compared to abciximab and to exert effects beyond the inhibition of GP IIb/IIIa.