Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval.

BACKGROUND: The QT interval on the ECG is prolonged by more than 50 marketed drugs, an effect that has been associated with syncope and/or sudden cardiac death due to an arrhythmia. Because changes in heart rate also change the QT interval, it has become standard practice to use a correction formula, such as the Bazett formula, to normalize the QT interval to a heart rate of 60 bpm, that is, the rate-corrected QT or QTc. Numerous other formulas have been devised to make this correction, including the Fridericia, Hodges, and Framingham formulas. OBJECTIVES: The purpose of this study was to investigate how the Bazett formula and three other formulas influence assessment of the QT-prolonging effect of the potassium channel-blocking drug ibutilide. METHODS: Using a standardized physical activity protocol, the QT interval was assessed over a broad range of heart rates before and after an infusion of ibutilide (4.75 microg/kg) that produced a stable 15- to 20-ms QT prolongation in consenting normal subjects (9 men and 9 women). The QT interval was measured digitally over a range of heart rates from 60 to 120 bpm, and then four correction formulas (Bazett, Fridericia, Framingham, or Hodges) were applied. The uncorrected change in QT interval due to ibutilide was compared with the change using each of the formulas by repeated measures analysis of variance. RESULTS: At heart rates from 60 to 120 bpm, the Bazett and Fridericia correction formulas overestimated the change in QT in both men and women (P <.001). However, the Framingham and Hodges formulas did not alter the accuracy of the assessment of QT interval change. CONCLUSION: Rate correction of QT intervals using the standard Bazett and Fridericia formulas can introduce significant errors in the assessment of drug effects on the QT interval. This has implications for the clinical assessment of drug effects and for the safety assessment of new drugs under development.     

The Effect of Anti-Tuftsin Antibody on the Phagocytosis of Bacteria by Human Neutrophils

Tuftsin (Thr-Lys-Pro-Arg) is a naturally occurring tetrapeptide which stimulates most known functions of the polymorphonuclear and mononuclear phagocytic cell lines. Although tuftsin is a well characterized bioactive peptide, the exact physiological role tuftsin plays remains unclear. Specific mouse anti-tuftsin antiserum generated in our laboratory, is now available for phagocytosis inhibition studies. Monolayers of human neutrophils were prepared on glass coverslips from a few drops of finger prick blood obtained from a single healthy donor. The monolayers were treated with and without mouse anti-tuftsin antiserum at dilutions of 1:1000 or 1:2000. Exogenous tuftsin (1 μg/ml) was also added with and without antibody. Treated and untreated neutrophils were subsequently incubated with unopsonized Staphylococcus aureus. The proportion of cells accomplishing phagocytosis (phagocytic index) and the number of bacteria engulfed per cell (avidity index) were recorded. The results showed that exogenous tuftsin increased phagocytosis while the addition of mouse anti-tuftsin antiserum at a 1:1000 dilution inhibited phagocytosis both with and without exogenous tuftsin. This effect was diminished by the antiserum at the 1:2000 dilution. This study reaffirms that tuftsin plays an important physiological role in phagocytosis.     

Combining spin echoes with gradient echoes in the context of the global coherent free precession pulse sequence.

To extend the signal longevity of magnetically excited spins in flowing fluids while in a state of global coherent free precession (GCFP), a refocusing radiofrequency (RF) pulse and bipolar gradient waveforms were combined with the GCFP sequence. The data demonstrate that RF refocusing in the presence of flowing blood is possible, but the improvement in signal amplitude depends on the static magnetic field homogeneity along the direction of motion and the displacement of the spins between the excitation and the RF refocusing pulse, as well as displacement during subsequent RF refocusing pulses. The least amount of phase dispersion and thus the longest lasting signal is obtained with the shortest echo spacing where only one line of data is recorded between two RF refocusing pulses. This approach was successfully used in a phantom and in vivo to image fast and slow blood flow. Depending on the experimental conditions, signal persistence is improved significantly compared to playing the same sequence without RF refocusing, but the improvement is limited by the product of blood flow velocity and the time between RF refocusing pulses.     

Sexual sequelae of antihypertensive drugs: Treatment effects on self-report and physiological measures in middle-aged male hypertensives

Antihypertensive drugs are commonly associated with adverse side effects in both clinical and laboratory studies. We investigated the sexual sequelae of several major classes of antihypertensive drugs (e.g., beta blockers, central alpha agonists, diuretics) in normal males and in hypertensive patients. We compared the effects of four widely used agents (methyldopa, propranolol, atenolol, hydrochlorothiazide-triamterene) and placebo, in a selected sample of 21 sexually dysfunctional male hypertensives, 13 of whom completed all five phases of the study. Each study drug was administered for a 1-month treatment period, followed by a 2-week, single-blind washout phase, according to a randomized, Latin square crossover design. Dependent variables for the study included a broad range of hormonal, NPT, and self-report measures of sexual response. Results indicated a lack of consistent drug effects on measures of sexual response, although more frequent sexual and nonsexual side effects were observed with methyldopa and propranolol. As in our previous studies, age was negatively correlated with both hormonal and NPT measures, whereas changes in blood pressure were not significantly related to sexual function scores. Results do not support the hypothesis that sexually dysfunctional males are at greater risk for adverse sexual sequelae when treated with centrally active agents or diuretics.     

Horizontal cell axon terminals in growing goldfish

In the retina of teleost fish, cone horizontal cell axons penetrate the inner nuclear layer, where they enlarge into fusiform terminal swellings. The present study shows that horizontal cell axon terminals enlarge disproportionately during postembryonic growth of the retina in juvenile and adult goldfish: the relative volume of axon terminals increases almost 20-fold, while the volume of the entire retina increases only about fourfold during a 2-3-yr period. The enlarging axon terminals fill in the gaps created as the numerical density of nuclei in the inner nuclear layer falls. Horizontal cell axon terminals are thought to participate in cone-dominated visual pathways, although their precise role is unclear. The results of this study suggest that a comparison of horizontal cell function in small and large fish might help to resolve this issue.     

Role of nuclear cardiology for determining management of patients with stable coronary artery disease

Both radionuclide angiography and myocardial perfusion imaging provide important insights that determine the management of patients with stable coronary artery disease. Both nuclear cardiology procedures have clearly demonstrated use in the noninvasvie identification of severe (left main or three-vessel) coronary artery disease and the noninvasive assessment of prognosis and thereby determine which patients should be sent to coronary angiography. Both radionuclide angiography and myocardial perfusion imaging provide prognostic information that is independent of resting left ventricular function and coronary anatomy and thereby influence the decision regarding which patients should be sent to coronary revascularization. This review considers the evidence supporting the uses of these nuclear cardiology procedures and provides suggestions regarding their cost-effective application.