ABSTRACT
Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.
Subject(s)
Antibiotics, Antineoplastic/adverse effects , Biomarkers/blood , Heart Diseases/chemically induced , Idarubicin/adverse effects , Leukemia, Myeloid/drug therapy , Acute Disease , Adult , Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Creatine Kinase, MB Form/blood , Cytarabine/administration & dosage , Cytarabine/adverse effects , Echocardiography , Female , Humans , Idarubicin/administration & dosage , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/bloodABSTRACT
The case-report describes a 48-year-old-female patient with the patent ductus arteriosus with the following structural changes leading to the malignant arrhythmias manifested as a syncope. The patient was treated by Amplatzer occluder and the implantation of the cardioverter-defibrillator. The authors discuss the patent ductus arteriosus, arrhythmias and sudden cardiac death in the patients with the congenital heart disease in an adulthood.
Subject(s)
Ductus Arteriosus, Patent/diagnosis , Syncope/etiology , Tachycardia, Ventricular/complications , Ductus Arteriosus, Patent/complications , Ductus Arteriosus, Patent/therapy , Female , Humans , Middle Aged , Tachycardia, Ventricular/therapyABSTRACT
The effect of prenatal exposure to cyclophosphamide on postnatal somatic development and the function of the immune system was studied in random-bred ICR mice. In a dose of 1.2 mg (i.e. an average of 23.5 mg/kg pregnant female body weight), cyclophosphamide administered on the 16th day of gestation (a vaginal plug = day 1) caused both prenatal and postnatal retardation of growth. In the 3rd, 5th and 8th postnatal week, increased proliferation of the splenocytes of the experimental mice was observed in vitro, with changes in the intensity of their activation by Concanavalin A and lipopolysaccharide. In the 3rd week their capacity for activation by lipopolysaccharide was markedly lower than their activation by Concanavalin A and phytohaemagglutinin. No differences were observed between proliferation and activation of the splenocytes of the offspring of the control and the experimental mice at the age of 16 weeks. After depression at three weeks, the delayed type hypersensitivity reaction showed a tendency to increase; in the offspring of the experimental mice the haemagglutinin titre against sheep RBC was raised during the whole period of the investigation. At 16 weeks, the activity of peritoneal macrophages was likewise elevated.
Subject(s)
Cyclophosphamide/toxicity , Immunocompetence/drug effects , Prenatal Exposure Delayed Effects , Animals , Female , Mice , Mice, Inbred ICR , PregnancyABSTRACT
Measurements of the permeability coefficients of various compounds up-to a molecular weight of about 70,000 have shown clearly that membranes prepared from hydrolyzed polyacrylonitrile are about 10 times more permeable than those made of poly(2-hydroxyethyl) methacrylate. The higher permeability is probably due more to the higher water content (about 75%) than to the type of network. The high mechanical strength of the membranes and their good permeability to compounds possessing a comparatively high molecular weight seem to designate the material for some new applications in medicine.
Subject(s)
Acrylic Resins , Acrylonitrile , Membranes, Artificial , Nitriles , Dialysis , Hydrolysis , Permeability , Polyhydroxyethyl MethacrylateABSTRACT
Cartilage bone-marrow extract has stimulated the collagen formation of articular as well as sternal cartilage collagen in chick embryo. Collagen biosynthesis has been stimulated also in other investigated tissues, i.e. in cornea and sclera of chick embryo as well as in sponge granuloma of rats, where mainly formation of collagen type I was stimulated. Glycosaminoglycans formation has also been increased after administration of cartilage bone-marrow extract.
Subject(s)
Bone Marrow , Cartilage, Articular/metabolism , Cartilage , Collagen/biosynthesis , Tissue Extracts/pharmacology , Animals , Bone Diseases/metabolism , Cartilage, Articular/embryology , Chick Embryo , Glycosaminoglycans/metabolism , Granuloma/metabolism , RatsABSTRACT
The effects of a number of classical and modern antirheumatics on the biosynthesis of glycosaminoglycans and collagen were studied comparatively. The experimental results indicate that the antirheumatics deeply affect the metabolism of the main components of connective tissue. With regard to the methods used for testing, it may be stated that phenylbutazone, flufenamic acid, ibuprofen, mefenamic acid and trimetazone belong to the most effective of the entire series of antirheumatics tested.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Collagen/biosynthesis , Glycosaminoglycans/biosynthesis , Animals , Cattle , Glucosamine/metabolism , Male , Rats , Sulfates/metabolismABSTRACT
Diftalone showed a distinct inhibition effect on the collagen formation in sponge granuloma as well as in chick embryos articular cartilage. The inhibitory effect was expressed even in corneal and articular cartilage glycosaminoglycans (GAG) sulphation and GAG formation in granulation tissue. According to our previous results diftalone showed a similar inhibition of collagen and GAG biosynthesis as other effective antirheumatic drugs.
