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Biomedical subjects

G Helft

Publications and source records attributed to G Helft.

At least 55 records · Page 3Linked to original sources
PubMed1999

The heparin management test: a new device for monitoring anticoagulation during coronary intervention.

Whole blood coagulation analysers are widely used during percutaneous coronary interventions. The precise degree of anticoagulation in patients is important in this setting. The aim of this investigation was to compare the results obtained with ACT (Hemochron) and HMT, the Heparin Management Test (TAS) in patients undergoing percutaneous coronary interventions. Patients (n = 100) were enrolled prospectively. Each patient received 10,000 units of heparin. At the end of the procedure, the mean ACT was 284+/-31 seconds and the mean HMT was 292+/-33 seconds. The correlation between the two methods was highly significant (r = 0.64, p<0.001). The HMT correlates well with ACT values in patients undergoing percutaneous coronary interventions. Its use in the management of these patients should be considered.

Angina, Unstable↗
PubMed1999

Histopathology and pathogenesis of plaque instability and thrombus formation.

Our knowledge of the pathogenesis of plaque instability has undergone profound changes in recent years. Research in this field has been driven by the fact that atherosclerosis and its thrombotic complications continue to be the major cause of mortality and morbidity throughout the industrialized world. The different types of atherosclerotic lesions, mechanisms of atherosclerotic progression, plaque vulnerability and rupture are now better understood. This has led to evolution of therapeutic strategies designed to stabilize atherosclerotic plaque and to reduce progression. Further-more, knowledge of mechanisms leading to thrombosis after plaque rupture have led to the development of antithrombotic strategies to prevent and reduce complications arising from such an event. This review will describe the histopathology and pathogenesis leading to plaque instability, the factors associated with subsequent rupture and assess the role of thrombosis in the progression of atherosclerotic disease. We will focus on current therapeutic strategies to identify and reduce vulnerable plaques and speculate on future areas for research.

Journal Article↗
PubMed1999

[New thrombolytic agents in myocardial infarction].

Myocardial infarction is the result of thrombotic coronary artery occlusion. Although present-day thrombolytics have major value by increasing the frequency of reopening of arteries responsible for myocardial infarction, by preserving myocardial function and, thereby, significantly reduce mortality. Nevertheless, they are subject to the following limitations: 1) excellent arterial partency is only obtained in 50% of cases: 2) reocclusion occurs in 5 to 10% of cases; 3) severe complications such as cerebral haemorrhage are observed in about 0.5% of cases. Therefore, the search to improve thrombolytic agents is intense. This article reports the recent advances in concept and production of new thrombolytic agents. The most recent results concern the production of mutants of T-PA (tissue plasmogen activator). Of these mutants, the reteplase (r-PA) has already received authorization for its commercialisation. Other t-PA mutants under development (phase 3) include TNK-t-PA and lanoteplase. Over the last few years, there has been renewed interest in staphylokinase. The results of the initial clinical trials with this agent have also been reported. Paradoxically, the mode of action of thrombolytic agents has an inherent pro-thrombotic effect. This explains some of the interest for anti-thrombotic agents as an adjuvant treatment of thrombolysis. The initial results of the association of thrombolytics with new glycoprotein IIb/IIIa platelet inhibitors and anti-thrombin agents are reported.

Coronary Disease↗
PubMed1999

[Diagnosis and development of heparin-induced thrombocytopenia. Biological and clinical aspects].

Two types of thrombocytopenia occur during treatment with heparin: type I and type II heparin-induced thrombocytopenia (HIT). Type I HIT is due to a direct interaction between heparin and platelets. They are asymptomatic, occur early, mild and transitory. Type II HIT which is immunoallergic in nature is the most important complication of this treatment. The thrombocytopenia has a different presentation, acute with a fall in platelets over 30 per cent and is often associated with the occurrence or worsening of a venous or arterial thrombotic episode. The major problems of this secondary type are threefold: its recognition, its confirmation and its management should be as early as possible to avoid the development of often dramatic complications which compromise the prognosis. Laboratory investigations are required by highly reliable specialist laboratories following a careful clinical history. The natural history of the platelet count should enable the difficult diagnosis of HIT to be made more accurately. The treatment of confirmed HIT and/or symptomatic HIT often requires a multidisciplinary approach from a specialized team involving clinicians and hematologists. Two therapies with the benefit of large experience have just been obtained in France with marketing approval (AMM) for the management of HIT: danaparoid (Orgaran) and recombinant hidurin, lepirudin (Refludan). A declaration to the regional drugs monitoring center should not be omitted. In addition, each patient should be given a certificate confirming the immunallergy thus avoiding any further exposure with potentially dramatic consequences.

Anticoagulants↗
PubMed1998

Late coronary angioplasty and ventricular late potentials.

To assess the effect of successful late coronary angioplasty of an occluded infarct-related artery on the prevalence of ventricular late potentials, signal-averaged electrocardiograms were recorded in 123 consecutive patients surviving a first acute myocardial infarction (58 with and 65 without mechanical reperfusion of the occluded coronary artery). Multivariate analysis showed that successful reperfusion by late angioplasty of the infarct artery contributes to a decrease in the prevalence of late potentials.

Aged↗
PubMed1998

Comparison of activated clotting times to heparin management test for adequacy of heparin anticoagulation in percutaneous transluminal coronary angioplasty.

The aim of this study was to compare the activated clotting time (ACT) obtained with the Hemochron device and the Heparin Management Test (HMT) on a new automated whole-blood coagulometer, the Thrombolytic Assessment System, in patients undergoing angioplasty. Fifty patients undergoing balloon angioplasty were prospectively enrolled. The mean ACT after a 10,000 unit bolus of heparin was 283 +/- 39 sec at the end of the procedure. The mean HMT after 10,000 units of heparin was 286 +/- 31 sec at the end of the procedure in the same patients. The correlation between the two methods was significant (r = 0.6; P < 0.01). The HMT appears to correlate well with standard values obtained with the Hemochron ACT monitor in patients undergoing percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1998

The effects of talking, reading, and silence on the "white coat" phenomenon in hypertensive patients.

To explore the mechanisms of the "white coat" phenomenon, the effects of talking, reading, and silence were analyzed. Fifty essential hypertensive patients were randomly allocated to periods of stress talking and relaxing reading, alternating with three periods of silence. While talking, systolic/diastolic blood pressure increased sharply, from 142 +/- 0.7/97.7 +/- 0.5 mm Hg to 159 +/- 0.7/111 +/- 0.5 mm Hg (P < .0001). While reading, systolic/diastolic blood pressure decreased (P < .0001). Moreover, talking and reading had opposite residual effects. The silence and reading periods gave the best approximations of the daytime ambulatory period. The predictive value of clinical blood pressure can be improved if measured during a period without talking, thus decreasing the "white coat" phenomenon.

Adult↗
PubMed1998

Scanning direction and line bisection: a study of normal subjects and unilateral neglect patients with opposite reading habits.

Sixty normal dextrals (30 left-to-right and 30 right-to-left readers) and two left unilateral neglect patient with opposite reading habits performed a passive line bisection task. In order to study the effect of scanning direction on performance, subjects had to stop a mark moving on the to-be-bisected line either from the left to the right or in the opposite direction. Results showed that the position of the subjective middle was dependent upon the scanning direction of the line for all the subjects. A leftward deviation appeared for left to right scanning, whereas a rightward shift occurred when the mark moved from the right to the left. These results emphasize the role of scanning direction in space organization and are discussed with respect to the explanatory hypotheses of unilateral neglect.

Adolescent↗
PubMed1998

Comparative time course of thrombolysis induced by intravenous boluses and infusion of staphylokinase and tissue plasminogen activator in a rabbit arterial thrombosis model.

Staphylokinase (SAK), a protein with known profibrinolytic properties, has recently given encouraging results in acute myocardial infarction and in peripheral arterial occlusion. The aims of this study were to compare SAK with alteplase (recombinant tissue plasminogen activator rt-PA) in a rabbit arterial thrombosis model, in terms of femoral blood flow kinetics during and after thrombolysis, and to examine the biological effects of systemic fibrinolysis in vivo. We compared two modes of intravenous rt-PA administration, two modes of intravenous SAK administration and three different SAK dose regimens in a rabbit model of femoral artery thrombosis. The main finding was that the infusion of SAK following a single bolus administration gave statistically higher blood flow values than the infusion of the same dose of rt-PA following a single bolus administration (P < 0.05). In this experimental model, we also confirmed that SAK is a fibrin-specific and plasminogen-saving fibrinolytic agent at doses below 0.5 mg/kg. However, at higher doses (1.0 and 1.5 mg/kg), which are above usual therapeutic doses, SAK significantly reduced fibrinogen levels in a dose- and time-dependent manner (P < 0.05). These results indicate that SAK compares favorably with rt-PA in an rabbit arterial thrombosis model, yielding higher blood flow values. Moderate-dose SAK seems to be a fibrin-specific plasminogen activator, but in our model very high doses were associated with a decrease of fibrinogen.

Animals↗
PubMed1998

[Staphylokinase and its mutants: a new generation of thrombolytic agents].

Staphylokinase which is extracted from Staphylococci has been known for more than 40 years as a profibrinolytic compound. It has been obtained more recently by genetic engineering. Staphylokinase activates plasminogen into plasmin. It is a promising new thrombolytic agent for the treatment of acute myocardial infarction and thromboembolic disease in general. It is a fibrin specific thrombolytic agent which does not decrease plasma fibrinogen level in treated patients. However it is antigenic and the group of Louvain has made much effort to reduce its antigenicity without decreasing its thrombolytic activity. Mutants with a reduced antigenic activity have been recently obtained. These new thrombolytic agents could be superior to currently used drugs. Staphylokinase mutants could have a better benefit/cost ratio than other thrombolytic agents.

Amino Acid Sequence↗
PubMed1998

Relation between successful late coronary angioplasty of an occluded, infarction-related artery and lower prevalence of ventricular late potentials.

BACKGROUND: The effect of mechanical reperfusion of the infarction-related artery on ventricular late potentials (VLP) continues to be debated. OBJECTIVE: To assess the influence of successful late coronary angioplasty on the prevalence of VLP after acute myocardial infarction (AMI). METHODS: We studied 113 consecutive patients (97 men, 16 women, mean age 57 +/- 10.8 years) in whom the infarction-related artery was occluded (thrombolysis in myocardial infarction score 0 or 1) at the time of the initial coronary arteriography 10.9 +/- 6.4 days after a first AMI. Successful late angioplasty of the infarcted artery was performed in 55 patients a mean of 11.5 +/- 7.2 days after AMI. The remaining 58 patients received a conservative treatment. Signal-averaged electrocardiograms (SAECGs) were recorded 25 +/- 10.2 days after AMI. Multivariate analysis was undertaken to assess the influence of late coronary angioplasty with respect to age, sex, infarction site, angiographic ejection fraction, extent of diseased coronary arteries, thrombolysis and time of recording the SAECG. RESULTS: The overall prevalence of VLP was 27%. It was greater in patients without than in those with angioplasty (40% compared with 15%, P = 0.017). Multivariate analysis demonstrated that successful angioplasty (odds ratio 3.2; P = 0.019) and ejection fraction >0.4 (odds ratio 5.1; P = 0.0051) were the strongest independent predictors of an absence of VLP. 'Non-inferior' myocardial infarction was also correlated with the absence of VLP (odds ratio 2.6), but with borderline significance (P = 0.053). CONCLUSION: When performed in an occluded, infarction-related artery, successful late coronary angioplasty contributes to a significant decrease in the prevalence of VLP.

Aged↗
PubMed1998

[Staphylokinase].

Myocardial infarction is due to thrombotic occlusion of a coronary artery. Current thrombolytic agents have demonstrated their major value by inducing a significant reduction of mortality, but they nevertheless present certain limits: 1) excellent arterial patency is obtained in only about 50% of cases; 2) reocclusions persist in 5 to 10% of cases; 3) very severe complications, such as cerebral haemorrhages, have not disappeared (about 0.5% of cases). There is therefore a large field of action for development of the optimal thrombolytic agent. Research concerning staphylokinase, classified among third generation thrombolytic agents, is therefore situated in this context. Staphylokinase is a protein known to possess profibrinolytic properties for more than four decades, but has been the subject of renewed interest over recent years. This article reviews the characteristics, mechanism of action and fibrinolytic properties of staphylokinase. It recalls the main results obtained in animal models and summarizes the main clinical trials in man.

Animals↗
PubMed1997

Comparative effects of recombinant staphylokinase and streptokinase on platelet aggregation.

Recombinant staphylokinase (RSTA) has been shown to offer promise as a thrombolytic agent. In contrast to streptokinase (SK), few studies have been devoted to possible effects of RSTA on platelets. We have compared the capacity of RSTA and SK to trigger platelet aggregation and to modify ADP (2.5 microM) response in platelet-rich plasma (PRP) of 125 healthy subjects. Thus, exposure of PRP to SK (40 to 50 micrograms/ml) induced platelet aggregation in 6 out of 25 subjects. However, under the same conditions, RSTA failed to induce platelet aggregation in all cases (25 out of 25 subjects). In contrast to RSTA, SK (0.4 to 50 micrograms/ml) greatly reduced ADP-induced platelet aggregation in 12 out of 25 subjects. Preincubation of plasma with SK is associated with a decrease in the fibrinogen concentration. Furthermore, there was a good correlation between SK-induced fibrinogenolysis and SK-induced platelet aggregation defect (r2 = 0.9; p = 0.001). No fibrinogenolysis was observed when different amounts of RSTA (0.4 to 50 micrograms/ml) were incubated in plasma for one min. However, there was a marked decrease in fibrinogen level (about 50%) when the plasma was incubated for five min with a very high concentration of RSTA. SK markedly enhanced the platelet response to ADP in 13 out of 25 subjects. In PRP of 6 out of 25 subjects, SK induces platelet aggregation and potentiates platelet response to ADP, however in PRP of 7 out of 25 subjects, SK caused only the increase of platelet response to ADP. The monoclonal antibody anti-Fc gamma RIIa1, I-3 (2 micrograms/ml), abolished SK-induced platelet aggregation and SK-enhanced ADP-induced platelet aggregation. In all cases (25 out of 25 subjects), RSTA failed to potentiate platelet response to ADP. These findings confirm that RSTA has a lesser fibrinogenolytic ability than SK and suggest its negligible effect on platelet function.

Adenosine Diphosphate↗
PubMed1997

[Anti-streptokinase antibodies].

The use of thrombolytics has significantly improved the management of patients with acute myocardial infarction but available molecules remains imperfect: restoration of normal coronary patency in about half the cases, risks of reocclusion, risk of bleeding. Streptokinase (SK), which is the least expensive agent, has disadvantages as do the other thrombolytics. SK, an immunogenic bacterial protein, has another feature: administration of SK leads to an immunitory response with the production of specific anti-streptokinase antibodies. These anti-streptokinase antibodies may interfere with the future administration of a compound containing SK either by inducing an allergic response or by neutralising the SK and making it ineffective. Moreover, anti-streptokinase antibodies, the result of previous streptococcal infections, are present in the circulation. Although the prevalence of anti-streptokinase antibodies in the general population, especially coronary patients at risk of myocardial infarction, is not well known and their potentially harmful effects are even less well known. In particular, the platelet aggregant effect in vitro of these antibodies in the presence of SK was not taken into account in the trials studying the influence of anti-streptokinase antibodies in the results of thrombolysis by SK. The anti-lytic effect of anti-streptokinase antibodies is well documented. For this reason, it is not recommended to readminister SK in patients who have previously been thrombolysed with a product containing SK.

Antibodies, Bacterial↗