[Early detection of cardiotoxicity of anthracyclines. Value of isotopic method]. / Détection précoce de la toxicité cardiaque des anthracyclines. Intérêt de l'étude isotopique.

Anthracyclines are antitumoral agents whose therapeutic efficacy is limited by dose-dependent cardiotoxicity. Thirty-one adult patients treated with long-term anthracycline were included in a prospective study to evaluate the ejection fraction and certain parameters of left ventricular diastoclic function by radionuclide angiography, and the left ventricular phase by Fourier's method. Scintigraphic acquisitions were obtained before starting and four weeks after ending chemotherapy. A significant decrease in the maximal velocity of early diastolic filling (2.84 +/- 0.57 to 2.49 +/- 0.45 VTD/s; p < 0.01), the ejection fraction also fell from 57.6% +/- 4.7% to 53.8% +/- 4.6% (p < 0.01). No significant changes in early diastolic filling time or analysis of left ventricular phase with respect to standard deviation (p > 0.05) were observed. In addition, the change in maximal velocity of early diastolic filling did not correlate with the reduction in ejection fraction. Therefore, left ventricular diastolic dysfunction is probably an early marker for anthracycline cardiotoxicity, the sensitivity of which is close to that of the ejection fraction in the detection of infraclinical cardiotoxicity.

[Subcutaneous recombinant hirudin in the treatment of deep venous thrombosis. A pharmacokinetic study]. / Hirudine recombinée par voie sous-cutanée dans le traitement de la thrombose veineuse profonde constituée. Etude pharmacocinétique.

Recombinant hirudin (HBW 023) has a pure and specific antithrombotic activity. It could be more effective than heparin in the treatment of deep venous thrombosis. Its half life is about three hours when administered intravenously which requires continuous infusion whereas subcutaneous administration can ensure stable plasma concentrations and antithrombotic activity over a period of approximatively 12 hours. The aim of the study was to check the safety and clinical and radiographic efficacy of recombinant hirudin administered subcutaneously to patients with recent deep venous thrombosis and to analyse the pharmacokinetics of the product and its effects on tests of coagulation. Ten patients were treated with 0.75 mg/kg of subcutaneous recombinant hirudin twice a day for 5 days. Anticoagulation was performed with standard heparin and acenocoumarol. Bilateral phlebography, pulmonary angiography or ventilation and perfusion scintigraphy were carried out before and on the 5th day of recombinant hirudin treatment. The activated cephalin time and standard anticoagulant tests and the plasma kinetics of recombinant hirudin were assayed between the 1st and 12th hour on the first and fifth days of treatment. The clinical course was simple in all but one patient who had a recurrence of pulmonary embolism on the 4th day justifying thrombolytic treatment. No haemorrhagic complications or secondary biological effects were observed. On the 5th day, control phlebography was unchanged or improved in all patients. The peak plasma concentration of recombinant hirudin was observed between the 3rd and the 4th hour following subcutaneous injection. The activated cephalin time was increased in parallel with increased concentrations of recombinant hirudin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy and safety of thrombolytic therapy in the elderly with severe pulmonary embolism]. / Efficacité et sécurité d'emploi du traitement thrombolytique chez les sujets âgés avec embolie pulmonaire grave.

Thrombolytic therapy leads to more rapid dissolution of thrombi in severe pulmonary embolism than conventional heparin therapy but is considered with much reserve in elderly patients because of the risk of haemorrhage, which is thought to be potentially greater in these subjects. The object of this study was to assess the efficacy and safety of thrombolytic therapy in patients over 70 years of age with severe pulmonary embolism, compared with patients under 70 years of age with the same condition. Eighty-nine patients with severe pulmonary embolism (Miller score > 17/34) were prescribed thrombolytic therapy in the absence of a contraindication without taking age into consideration. Fifty-three were under 70 years of age (54 +/- 15; range: 18 to 70 years) and 36 were over 70 years of age (78 +/- 5; range: 71 to 88 years). Apart from age, there was no difference in the clinical presentation of the two groups. Thrombolytic therapy was initiated with streptokinase 100,000 IU/hr for twelve hours after an initial bolus of 250,000 IU or with urokinase or plasminogen tissue activator in cases with a contraindication to streptokinase. An uncomplicated course was observed in the same percentage of cases in the two groups. The Miller score and mean pulmonary pressures fell in the same way in the two groups. Three patients died during the hospital period, two aged under 70 (3.7%) and one over 7 years of age (2.7%). Major bleeding occurred in 3 subjects under 70 (5.6%) and 5 subjects over 70 (13.8%) (p = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

[Anticoagulant therapy with recombinant hirudin in patients with thrombopenia induced by heparin]. / Traitement anti-thrombique par hirudine recombinante chez des patients ayant une thrombopénie induite par l'héparine.

OBJECTIVES: Heparin-induced thrombocytopenia is an uncommon and severe complication of heparin therapy. Both venous and arterial thromboembolic events can occur, requiring withdrawal of the heparin therapy. When anticoagulant therapy is mandatory, recombinant hirudin can be used. METHODS: We used recombinant hirudin (HBW 023) in 6 patients with heparin induced thrombocytopenia. In case of venous thromboembolism, an initial intravenous bolus (0.07 mg/kg) was followed by continuous infusion (0.05 mg/kg/h); for arterial thromboembolism the initial bolus was 0.7 mg/kg and infusion rate 0.15 mg/kg/h. When possible oral anticoagulants were started and hirudin withdrawn when the INR ratio reached 3. RESULTS: The clinical course was uneventful in all 6 patients. There was no recurrent thromboembolism. Cephalin-activated coagulation time (patient/control) varied between 1.8 and 3.5 (median 2.4) during hirudin administration. Platelet count rose to the nadir (median 70 x 10(9)/l, range 15-90) reaching over 100 x 10(9)/l in all patients between the third and sixth day (median 5 days) after stopping heparin. CONCLUSION: Intravenous administration of hirudin provides effective immediate anticoagulation in patients with heparin-induced thrombocytopenia, thus allowing conversion to oral anticoagulants without risking recurrent thromboembolism.