Inhibition of Tumor Growth with Ultralow Doses of Doxorubicin under Experimental Conditions

Antitumor activity of ultralow doses of cytostatic doxorubicin was studied on BDF1 mice with Lewis lung carcinoma. The preparation was injected intraperitoneally in single doses of 10^-5, 10^-10, 10^-15, and 10^-20 M on the next day after tumor inoculation. The effect of ultralow doses was compared with that of a standard therapeutic dose of doxorubicin (8 mg/kg, 1.4×10^-3 M). Doxorubicin in ultralow doses produced an antitumor effect comparable with that induced by the preparation in standard doses. On day 12 after administration of doxorubicin in ultralow and standard doses, tumor size in mice did not exceed 20% of the control level.     

Disorders of cardiac rhythm in combined ventricular pre-excitation syndrome and primary mitral valve prolapse

Primary prolapse of the mitral valve was diagnosed in 27 (11.7%) out of 230 patients with preexcitation syndrome: 10 of them presented with Wolff-Parkinson-White syndrome, 15 with Clerc-Lévy-Critesco syndrome, and two patients with combination of both syndromes. Preexcitation syndrome combined with mitral valve prolapse manifested itself by different disorders of the cardiac rhythm, mainly by the supraventricular forms: by PST in 17, nonparoxysmal tachycardia in 1, atrial fibrillation paroxysms in 7, sinus tachycardia in 2, supraventricular extrasystole in 3, pacemaker migration in the atria in 1 patient. Clerc-Lévy-Critesco syndrome initiated with atrial fibrillation paroxysms in 7 patients with mitral valve prolapse and with the enlargement of the left atrium. The prognostically unfavourable varieties of the preexcitation syndrome and mitral valve prolapse manifested themselves in ventricular tachycardia progressing to ventricular fibrillation, paroxysmal supraventricular tachycardia with a high frequency of ventricular contractions up to 213-230 and atrial tachyarrhythmia up to 250-280 per minute, which were regarded as factor at risk for potential transformation to ventricular tachycardia; as well as in continuously recurrent attacks of arrhythmia in the presence of multiple AV additional tracts or combined with sinoatrial and atrioventricular block.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Prospective course of therapy arresting attacks of atrial fibrillation in patients with preexcitation syndromes]

A comparative study of antiarrhythmic drugs was performed in 81 patients with atrial fibrillation attacks in the presence of preexcitation syndrome. The first intravenous administration of cordarone was effective in 84.06%, disopyramide--in 69%, ajmaline in 44.8, verapamil in 42.1, novocaine amide in 39.4 and ethacizin in 38.5% of the patients. The first oral administration of quinidine and kinilentin arrested 80.4% of arrhythmia attacks, disopyramide 66.7% propranolol and mexitil 37.5 and 33.3%, respectively. Prospective evolution of antiarrhythmic therapy manifested with decreased therapeutic efficacy of the drugs from 55.7 to 26.2% in the whole group during the period of 1-5 years.