Activity of some naphthoquinones on blood stream forms of Trypanosoma cruzi

Accidental transmission of Chagas disease to man by blood transfusion is a serious problem in Latin America. This paper describes the testing of several naphthoquinones, some of which were active against blood trypomastigotes in vitro at 4 degrees C and might therefore warrant further study for preventing transmission of Chagas disease by blood transfusion.     

Onset of spermatozoal degeneration in low-fertility Delaware roosters and test for autoimmune basis

The objectives of this study were 1) to determine the onset of a heritable reproductive disorder in the rooster that is characterized by extensive spermatozoal degeneration within the ductus deferens, and 2) to determine if autoimmunity was associated with spermatozoal degeneration. Seventy-five percent of the affected roosters did not ejaculate large percentages of degenerate spermatozoa at 20 wk of age, approximately the age of sexual maturity. Rather, seminal quality gradually declined over the next 6 wk, as both ejaculate volume and number of spermatozoa ejaculated increased. The evaluation of testicular and excurrent duct tissues via immunofluorescence failed to reveal either IgY or IgA associated with spermatozoa. While histological examination revealed greater lymphocyte numbers (P less than .05) in the proximal ductus deferens, these cells were not associated with spermatozoa nor spermatozoal clumping. While spermatozoal degeneration tends to be latent at the onset of semen production, it does not appear to be due to spermatozoal autoimmunity.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.     

Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk

THIS IS THE FIRST OF 2 ARTICLES EVALUATING cardiac events in patients undergoing noncardiac surgery. In this article, we review the magnitude of the problem, the pathophysiology of these events, approaches to risk assessment and communication of risk. The number of patients undergoing noncardiac surgery worldwide is growing, and annually 500 000 to 900 000 of these patients experience perioperative cardiac death, nonfatal myocardial infarction (MI) or nonfatal cardiac arrest. Although the evidence is limited, a substantial proportion of fatal perioperative MIs may not share the same pathophysiology as nonoperative MIs. A clearer understanding of the pathophysiology is needed to direct future research evaluating prophylactic, acute and long-term interventions. Researchers have developed tools to facilitate the estimation of perioperative cardiac risk. Studies suggest that the Lee index is the most accurate generic perioperative cardiac risk index. The limitations of the studies evaluating the ability of noninvasive cardiac tests to predict perioperative cardiac risk reveals considerable uncertainty as to the role of these popular tests. Similarly, there is uncertainty as to the predictive accuracy of the American College of Cardiology / American Heart Association algorithm for cardiac risk assessment. Patients are likely to benefit from improved estimation and communication of cardiac risk because the majority of noncardiac surgeries are elective and accurate risk estimation is important to allow informed patient and physician decision-making.     

Functionalization of poly(methyl methacrylate) by free radical polymerization, 1. Transfer with functional thiols

Chain transfer constants (C_tr) for three phosphonated thiols in methyl methacrylate (MMA) polymerization at 60°C were determined from measurements of the degree of polymerization. These thiols were: diethyl 2-mercaptoethyl phosphate ( 1 ), diethyl 2-mercaptoethylamidophosphate ( 2 ), and tetraethyl mercaptomethylethylene bis(phosphate) ( 3 ). Transfer efficiencies of the thiols were found to be dependent upon their structures. The C_tr value of thiol 2 with MMA was the lowest in the present series, which can be attributed to a possible charged tautomeric form which eventually may reduce the electron density on the thiol, thus rendering the chain transfer reaction with the PMMA radical less feasible. C_tr values of thiol 1 were evaluated at 55, 60, 65, 70 and 75°C. This thiol behaves as an “azeotropic” transfer agent for MMA at 96°C.     

Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.