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Biomedical subjects

D Gulba

Publications and source records attributed to D Gulba.

At least 19 recordsLinked to original sources
PubMed2003

Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE).

OBJECTIVE: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). DESIGN: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. SETTING: Ninety four hospitals of varying size and capability in 14 countries across four continents. PATIENTS: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30-60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). RESULTS: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. CONCLUSION: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction.

Adult↗
PubMed2001

Plasminogen activator inhibitor type-1 in cardiovascular disease. Status report 2001.

Plasminogen activator inhibitor type-1 (PAI-1) is known to contribute to thrombus formation and to the development and the clinical course of acute and chronic cardiovascular disease, as well as of other arterial and venous thromboembolic diseases. Recently, an important role of elevated pretreatment levels of PAI-1 for failure of thrombolytic therapy of acute myocardial infarction has been discussed. PAI-1 plasma levels depend on the one hand on gene regulation but are related on the other hand to known risk factors of atherosclerosis like insulin resistance, diabetes or hypertriglyceridemia, respectively. Furthermore, an activated renin-angiotensin-aldosterone system (RAAS) significantly contributes to the upregulation of PAI-1 concentration via a receptor-mediated mechanism. In accordance to the known mechanisms of regulation of PAI-1 plasma levels, the use of specific agents like antidiabetic drugs, fibrates, statins, ACE inhibitors and angiotensin II type-1 receptor-blockers may contribute to the downregulation of circulating PAI-1 and, therefore, increase the fibrinolytic capacity and consecutively counteract the thrombotic tendency. To further improve the efficacy of thrombolytic therapy, a PAI-1 resistant variant of t-PA, TNK-t-PA, has been developed and is now available for acute myocardial infarction.

Antifibrinolytic Agents↗
PubMed2001

Amelioration of angiotensin II-induced cardiac injury by a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. METHODS AND RESULTS: We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription-polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-kappaB and AP-1 were substantially less activated, although plasma cholesterol was not decreased. CONCLUSIONS: These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

Angiotensin II↗
PubMed2000

Angiotensin II (AT(1)) receptor blockade reduces vascular tissue factor in angiotensin II-induced cardiac vasculopathy.

Tissue factor (TF), a main initiator of clotting, is up-regulated in vasculopathy. We tested the hypothesis that chronic in vivo angiotensin (ANG) II receptor AT(1) receptor blockade inhibits TF expression in a model of ANG II-induced cardiac vasculopathy. Furthermore, we explored the mechanisms by examining transcription factor activation and analyzing the TF promoter. Untreated transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR) feature hypertension and severe left ventricular hypertrophy with focal areas of necrosis, and die at age 7 weeks. Plasma and cardiac ANG II was three- to fivefold increased compared to Sprague-Dawley rats. Chronic treatment with valsartan normalized blood pressure and coronary resistance completely, and ameliorated cardiac hypertrophy (P < 0.001). Valsartan prevented monocyte/macrophage infiltration, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) activation, and c-fos expression in dTGR hearts. NF-kappaB subunit p65 and TF expression was increased in the endothelium and media of cardiac vessels and markedly reduced by valsartan treatment. To analyze the mechanism of TF transcription, we then transfected human coronary artery smooth muscle cells and Chinese hamster ovary cells overexpressing the AT(1) receptor with plasmids containing the human TF promoter and the luciferase reporter gene. ANG II induced the full-length TF promoter in both transfected cell lines. TF transcription was abolished by AT(1) receptor blockade. Deletion of both AP-1 and NF-kappaB sites reduced ANG II-induced TF gene transcription completely, whereas the deletion of AP-1 sites reduced transcription. Thus, the present study clearly shows an aberrant TF expression in the endothelium and media in rats with ANG II-induced vasculopathy. The beneficial effects of AT(1) receptor blockade in this model are mediated via the inhibition of NF-kappaB and AP-1 activation, thereby preventing TF expression, cardiac vasculopathy, and microinfarctions.

Angiotensin II↗
PubMed1999

Plasmin activation system in restenosis: role in pathogenesis and clinical prediction?

During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis and restenosis. Responsible pathophysiologic mechanisms, however, remain elusive. This review focuses primarily on the clinicians, point of view, suggesting that increases in plasminogen activator inhibitor type-1 (PAI-1) plasma levels after balloon angioplasty or permanently elevated lipoprotein (a) (Lp(a)) plasma levels might be helpful in the prediction of restenosis after coronary angioplasty. In contrast, tissue-type plasminogen activator (tPA) plasma levels appear unrelated to restenosis, and data regarding a possible role of urokinase-type plasminogen activator (uPA) in circulation are not available at present. Furthermore, a new hypothesis on the pathophysiological role of local PAI-1 overexpression as a beneficial negative feedback mechanism to limit excess cellular proliferation in atherogenesis and restenosis is presented.

Angioplasty, Balloon, Coronary↗
PubMed1999

Differentiation of low molecular weight heparins in acute coronary syndromes: an interventionalist's perspective.

The more predictable and sustained anticoagulant effects of low molecular weight heparins (LMWHs) compared with unfractionated heparin (UFH) has led to increasing interest in their potential use in association with interventional cardiac procedures. Available data demonstrate that dalteparin, nadroparin, reviparin and enoxaparin can be safely used during percutaneous transluminal coronary angioplasty. As yet there is, however, no evidence of a reduction in restenosis. Preliminary evidence indicates that a novel antithrombotic combination of ticlodipine and enoxaparin in association with coronary stenting may reduce the frequency of acute events compared with conventional antithrombotic therapy, although it remains unclear as to whether ticlopidine alone is equally effective. Enoxaparin also reduces the frequency of ischemic events following thrombolytic therapy for acute myocardial infarction, and is the only LMWH to have been shown to reduce the frequency of revascularization procedures in patients with acute coronary syndromes. Some evidence suggests that, in patients with acute coronary syndromes, plaque passivation may be adequately managed using long-term LMWH therapy, rather than immediate intervention, given the potential increase in thromboembolic burden by the interventional procedure. On the basis of available evidence, peri-interventional use of LMWH is broadly feasible. Given the United States Food and Drug Administration's position that LMWHs are distinct noninterchangeable drugs, further trials are needed to establish acceptable protocols and the LMWH of choice. Until that time, interventional cardiologists can rely on available clinical data to choose a LMWH that will simplify patient management and improve patient outcome.

Acute Disease↗
PubMed1998

Angiotensin II and coronary artery disease, congestive heart failure, and sudden cardiac death.

An activated renin-angiotensin system is a major risk factor for cardiovascular events. Angiotensin II acts on AT1 and AT2 receptors. Stimulation of AT1 receptors is associated with endothelial dysfunction, mainly as the consequence of an increased vascular production of superoxide radicals, vasoconstriction, platelet activation, enhanced release of plasminogen activator inhibitor-1, activation of immediate early genes c-fos and c-jun, myocyte hypertrophy, connective tissue formation, endothelin-1 synthesis, and activation of growth factors like PDGF and TGF-beta 1. Stimulation of AT2 receptors can mitigate or abolish the growth promoting effects of AT1 receptor stimulation. The contribution of these effects--single or in combination--on the progression of atherosclerotic lesions, the phenomenon of restenosis and the process of remodeling in heart failure is being progressively elucidated. With increasing knowledge about these relationships the inhibition of AT1 receptors appears as a main target in preventive and reparative strategies in cardiovascular diseases.

Angiotensin II↗
PubMed1998

Use of abciximab in interventional cardiology.

The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated. One key issue is selection of patients who may benefit from GP IIb/IIIa receptor blockade. Focusing specifically on abciximab, data from three large-scale, randomized trials demonstrate that abciximab is appropriate for all patients undergoing percutaneous transluminal coronary angioplasty, regardless of risk stratum. Other important issues to consider when prescribing this therapy include benefits in conjunction with stents and new devices, dosing and timing of administration, and the role of prophylactic versus "bailout" administration. This article reflects a distillation of the views and consensus regarding the use of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Abciximab↗
PubMed1998

Use of abciximab in interventional cardiology.

The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated. One key issue is selection of patients who may benefit from GP IIb/IIIa receptor blockade. Focusing specifically on abciximab, data from three large-scale, randomized trials demonstrate that abciximab is appropriate for all patients undergoing percutaneous transluminal coronary angioplasty, regardless of risk stratum. Other important issues to consider when prescribing this therapy include benefits in conjunction with stents and new devices, dosing and timing of administration, and the role of prophylactic versus "bailout" administration. This article reflects a distillation of the views and consensus regarding the use of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Abciximab↗
PubMed1997

[Clinical safety using the thrombocyte aggregation inhibitor c7E3 in interventional cardiology in 520 patients].

The monoclonal antibody c7E3 (ReoPro) is a highly selective inhibitor of platelet aggregation that binds to the fibrinogen receptor (GP IIb/IIIa) on the surface of platelets and leads to a dose-dependent, nearly complete inhibition of platelet aggregation. The clinical value of c7E3 to reduce ischemic events after PTCA in addition to heparin and aspirin has been demonstrated in the EPIC-, EPILOG-, and CAPTURE-trial. In these studies, c7E3 was associated with an increased bleeding risk after the coronary intervention. The DTREO-Trial (German trial with c7E3) was designed as a prospective study to investigate the clinical safety of c7E3 in the daily routine of a cath lab. From April 1995 through September 1996 520 patients were enrolled at 30 German sites. c7E3 was mainly used in patients with acute coronary syndromes (55% unstable angina Braunwald Class I-III and C; 28% in acute myocardial infarction) and in patients with complex coronary lesions (AHA/ACC classification type B and C lesion in 84% of the study group). In 51% of the interventions a stent was implanted (25% in bailout-situations and in 26% as an elective intervention) and c7E3 was used as an adjunctive to prevent sub-acute stent thrombosis. The incidence of "major" bleeding events (TIMI-classification) was less frequent in this study as in the EPIC-trial and comparable to the results of the EPILOG- and CAPTURE trial. In conclusion this study confirms the positive risk profile of c7E3 in patients undergoing high-risk percutaneous revascularization procedures.

Abciximab↗
PubMed1996

New approaches in plasminogen activator therapy.

Large efforts have been undertaken to develop more effective and safer thrombolytic agents than those currently used in clinical practice. In addition, the value of adjunctive agents influencing thrombotic and thrombolytic processes could be shown and newer agents are under active investigation. This review focuses on theoretical and practical aspects of optimizing thrombolytic therapy and mainly on genetically engineered, third generation plasminogen activators. Optimized thrombolytic therapy may make this form of therapy available to patients that are currently considered ineligible and it may lead to earlier, more complete reperfusion of infarct related coronary arteries. The benefits and risks of optimized thrombolytic regimens relative to mechanical reperfusion strategies will have to be constantly reassessed as both forms of treatment develop.

Fibrinolytic Agents↗
PubMed1996

Thrombolytic therapy in acute myocardial infarction--update 1996.

Despite the major advances made over the last decade, mortality following acute MI is still high for patients even if treated with the so far most effective "front-loaded" rt-PA regimen: 30-day-mortality is 6.3% and is associated with fatal cerebral haemorrhage in 1.5%. Further improvement of short- and long-term prognosis can be achieved if infusion of the thrombolytic agent starts early, if reperfusion occurs more rapidly and if a persistent TIMI grade 3 flow of the infarct-related artery can be achieved. These are prerequisites for optimal preservation of ventricular function and predictors of a favourable outcome.

Acute Disease↗
PubMed1996

Restenosis following percutaneous revascularization--the potential role of thrombin and the thrombin receptor.

Thrombin is present at sites of vascular injury and elicits many effects which may contribute to neointimal growth. Further studies are needed to order to determine steps involved in thrombin-induced effects and to identify potential sites to regulate these effects. The failure of the Helvetica trial to demonstrate an effect of treatment with hirudin on restenosis may relate more to our inability to safely inhibit thrombin than to a lack of a role for thrombin in restenosis. A therapy which enables safe and effective control of thrombin-induced responses following vascular injury may yet prove effective at reducing restenosis following percutaneous coronary revascularization.

Angioplasty, Balloon, Coronary↗
PubMed1994

Treatment of portal vein thrombosis by thrombectomy and regional thrombolysis.

BACKGROUND: Portal vein thrombosis is a rare disorder. The prognosis of both the acute and the chronic forms is determined by the resulting acute or chronic portal hypertension. The therapeutic approach of choice is controversial. METHODS: A case of etiologically unclear thrombosis of the portal vein system in a young man is reported, which was treated successfully by means of portal vein thrombectomy combined with intraoperative and postoperative thrombolysis with recombinant tissue plasminogen activator (rTPA). RESULTS: Initial thrombectomy established sufficient venous return. However, rethrombosis of the portal vein occurred 2 days later. In a second operation rethrombectomy was followed by intraoperative regional application of rTPA, which was continued after operation during a period of 48 hours through a catheter inserted in a mesenteric vein. Patency of the portal system was confirmed 1 week after the procedure. The 1-year follow-up reconfirmed this result (through indirect portography and Doppler sonography). The patient received the anticoagulant phenprocoumon. CONCLUSIONS: The combination of surgical thrombectomy and regional thrombolysis with rTPA could offer a feasible therapeutic option for selected patients with acute prehepatic portal vein thrombosis.

Acute Disease↗
PubMed1993

The Filcard temporary, removable vena cava filter: use in local thrombolytic therapy.

Femoral and iliac vein thrombosis with impending pulmonary embolism is a potentially life-threatening condition. The decision whether or not to implant a permanent caval filter always requires critical consideration of a number of factors. Improper positioning of the filter with resultant filtering inefficiency, thrombosis of the filter and of the cava, propagation of the thrombus through the filter, perforation by the filter of the vena cava with penetration of the aorta, the duodenum, the psoas muscle or the vertebral body, fragmentation of the filter and migration of the filter are well-documented complications of the currently available permanent filters. The danger of fatal pulmonary embolism has to be weighed against that of one or a combination of any of the above-mentioned possible complications associated with permanent caval filters which may affect the quality of later life. We present our initial observations with a temporary, removable inferior vena cava (IVC) filter in a young female patient with a floating thrombus in the left femoral and iliac vein who underwent successful local thrombolytic therapy.

Adolescent↗