Evaluation of cytotoxicity of some Mannich bases of various aryl and arylidene ketones and their corresponding arylhydrazones.

Mannich bases were synthesized and converted to the corresponding arylhydrazones. X-ray analysis of a ketone (1a) and a hydrazone (4d) revealed structural features of interest. All of the compounds showed cytotoxicity toward murine lymphocytic leukemia L1210 cells in the 4.9-25.0-microM range. The correlation coefficients generated by plotting the IC50 values (the concentrations of compounds that inhibit the growth of tumors by 50%) of some hydrazones against certain electronic, hydrophobic, and steric constants of the aryl substituents indicated only weak correlations. A few ketones and hydrazones displayed significant cytotoxicity to the WiDr human colon cancer cells, and these derivatives, especially the ketones, may serve as prototypes for future drug development. The KB tumor (a human epidermoid carcinoma of the nasopharynx) was somewhat refractory to selected compounds. In an in vitro assay conducted by the National Cancer Institute and involving approximately 53 tumor cell lines originating from eight neoplastic diseases, 65% of the compounds showed some selectivity toward one or more groups of cancers, principally leukemia, melanoma, and colon cancer. The bioevaluation of the ketones and hydrazones against the L1210, WiDr, and KB tumors, as well as evidence from proton nuclear magnetic resonance studies did not support the suggestion that hydrazones may be prodrugs of the corresponding ketones.     

Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation

Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18 +/- 0.06 U (scan 1) and 0.17 +/- 0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R = 0.76), interscan reproducibility (SD) was 0.03 U (R = 0.62), and overall reproducibility (SD) was 0.04 U (R = 0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n = 29) studied previously in this department. A change of greater than or equal to 0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF less than or equal to 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.     

High density lipoproteins, genetic polymorphism for apo A-I and coronary artery disease

HDL cholesterol and apolipoprotein A-I are associated with the development of coronary artery-disease (CAD). The presence of a PstI site polymorphism adjacent to the gene encoding apo A-I (known as P₂) has also been shown to be associated with CAD but this relationship is controversial. A case control study was conducted in an Australian population to re-examine whether the rare P₂ allele is associated with CAD. Data were derived from 159 cases of angiographically confirmed CAD and 99 healthy controls. The proportion of CAD cases carrying the P₂ allele did not differ significantly from controls (11% versus 9%). In a multiple logistic regression model controlling for the effects of age, country of birth, hypertension and hypotensive drugs, body mass index and lipid variables, the P₂ allele failed to predict significantly the presence of CAD (odds ratio 1.83; 95% confidence interval 0.65–5.19).     

Clinical Problems in Atrial Synchronous Ventricular Inhibited Pacing: A Long-term Follow-up of 54 Patients

Fifty-four VDD-paced patients were followed for more than 12 months; they were studied retrospectively in order to assess possible clinical problems and their management. The patients were between 19 and 84 years of age (mean, 66 +/- 11). Twenty-four of the 54 received a VDD pacemaker as a primary implant and 30 had had VVI pacemakers which were changed to VDD mainly because of limited exercise tolerance or symptoms of AV asynchrony. The follow-up time was between 12 and 69 months (mean, 39 +/- 17). Pacemaker and lead problems were neither frequent nor serious. Six patients had spontaneous paroxysmal supraventricular tachyarrhythmias, four had pacemaker-mediated supraventricular tachycardias and six had ventricular tachyarrhythmias. Treatment of tachyarrhythmias included drugs, DC conversion, reprogramming, or combinations of these measures. Frequency of hospitalization was not greater than expected. In conclusion, VDD pacing appears safe and reliable, with problems mainly associated with the underlying cardiac disease rather than to the pacing mode itself.     

A New Lead for Transvenous Atrial Pacing and Sensing Clinical and Electrophysiological Experiences

The Medtronic 6961 lead has been used in 14 patients for transvenous atrial sensing and/or pacing. This lead is furnished with small tines of silicone rubber at the distal end. The conductor coil material is space wound for flexibility. Thus, the lead lacks intrinsic elasticity and can be fastened within the right atrial appendage without a preformed J-shape. The clinical experiences with the lead are encouraging. The lead is easier to introduce and position in the right atrial appendage than the previously used tined J-shaped leads (Medtronic 6991). The small size of the new lead makes the choice of vein less critical and a normally-sized external jugular or cephalic vein permits the use of the same vessel for a second ventricular lead. By means of a lead extension wire, consecutive determinations of the P-wave amplitude, stimulation threshold of the right atrium, electrode resistance, and P/QRS-ratio were made for four weeks following electrode insertion. The mean P-wave amplitude at insertion was 4.9 +/- 1.5 mV (mean +/- SD). There was a significant decrease to a lowest mean level of 309 +/- 1.1 mV after one week. From that time there were only small variations. In the supine position and with normal breathing there was a spontaneous variation of the P-wave amplitude of +/- 12%. The P-wave amplitude was influenced by body position and maximal breathing movements to a minor extent. The threshold of stimulation was 0.9 +/- 0.4 V after one week. Later there was a small decrease in the threshold which, however, still remained significantly higher than at the time of insertion. The total resistance of the electrode system was about 700 ohms and P/QRS-ratio about 4 +/- 3. During an observation time ranging from 4 to 11 months there were no electrode dislocations. The electrodes were connected to the intended pacemakers without complications. In conclusion, the transvenous endocardial atrial lead, Medtronic 6961, shows attractive and promising qualities. The electrophysiological data recorded are suitable for the pacemakers in use. The electrode definitely deserves further evaluation.