Long-term ST database: a reference for the development and evaluation of automated ischaemia detectors and for the study of the dynamics of myocardial ischaemia.

The long-term ST database is the result of a multinational research effort. The goal was to develop a challenging and realistic research resource for development and evaluation of automated systems to detect transient ST segment changes in electrocardiograms and for supporting basic research into the mechanisms and dynamics of transient myocardial ischaemia. Twenty-four hour ambulatory ECG records were selected from routine clinical practice settings in the USA and Europe, between 1994 and 2000, on the basis of occurrence of ischaemic and non-ischaemic ST segment changes. Human expert annotators used newly developed annotation protocols and a specially developed interactive graphic editor tool (SEMIA) that supported paperless editing of annotations and facilitated international co-operation via the Internet. The database contains 86 two- and three-channel 24 h annotated ambulatory records from 80 patients and is stored on DVD-ROMs. The database annotation files contain ST segment annotations of transient ischaemic (1155) and heart-rate related ST episodes and annotations of non-ischaemic ST segment events related to postural changes and conduction abnormalities. The database is intended to complement the European Society of Cardiology ST-T database and the MIT-BIH and AHA arrhythmia databases. It provides a comprehensive representation of 'real-world' data, with numerous examples of transient ischaemic and non-ischaemic ST segment changes, arrhythmias, conduction abnormalities, axis shifts, noise and artifacts.

The relevance of nitrendipine erythrocyte partitioning for the variability of its bioavailability parameters.

The pharmacokinetic parameters of nitrendipine were determined in 40 healthy male volunteers and a very high degree of intersubject variability was observed (CV = 39-71%). Since the distribution of nitrendipine to erythrocytes could influence the overall pharmacokinetic variability the correlation between hematocrit and various pharmacokinetic parameters was analyzed, using linear regression. In vitro partitioning of nitrendipine to erythrocytes suspended in physiologic saline was studied over a range of hematocrit and drug concentration values. The correlations of in vivo pharmacokinetic parameters were linear with medium to high correlation coefficients (0.65-0.80). The positive correlation between the volume of distribution and hematocrit and negative between AUC, C(max) and beta parameters indicate that nitrendipine enters and/or is bound to erythrocytes. The results of the in vitro erythrocyte partitioning experiments confirm this observations as the mean values of partition coefficient to erythrocytes was found to be 2.85 +/- 0.17.

Kinetics of 4-fluoroquinolones permeation into saliva.

Following a single oral administration of ciprofloxacin, norfloxacin, pefloxacin and ofloxacin preparations to healthy volunteers simultaneously collected, saliva and plasma 4-fluoroquinolone concentrations were assayed by HPLC. Pharmacokinetic properties were determined by ordinary least squares fitting of the two compartment pharmacokinetic model to the experimental data. A good correlation between plasma and saliva data has been demonstrated. The saliva to venous plasma drug concentration ratio S/P appeared to be time-dependent in the case of norfloxacin and pefloxacin. It was demonstrated that S/P is a function of the quotient of the rate of absorption and venous plasma drug concentration. The calculated S/P ratios with the influence of absorption eliminated, (S/P)(corr) are: ciprofloxacin 0.53+/-0.02, norfloxacin 0.34+/-0.04, ofloxacin 0. 43+/-0.02 and pefloxacin 0.39+/-0.02 (mean+/-S.E.). These values are apparently independent of log D thus making it impossible to predict S/P on the basis of partition principles. The corresponding (S/P)(dif) ratios were calculated on the basis of the assumption that an equilibrium is established across the blood-saliva barrier, which is permeable only for nonionized and nonprotein bound drug fraction. Comparing (S/P)(corr) with the calculated (S/P)(dif) ratios it is evident that 4-fluoroquinolone permeation in saliva cannot be described by passive diffusion based on pH-partition theory.

Exertional syncope in a patient with aortic stenosis and right coronary artery disease.

A female with advanced aortic valvular stenosis and moderate right coronary artery disease experienced an exertional syncope during 24-h ambulatory electrocardiographic monitoring. A progressive bradycardia with 90-s sinus node arrest (cardio-inhibitory response) and premonitory angina pectoris with significant ST segment changes were demonstrated. Our report supports the concept of a neurocardiogenic (vasovagal) mechanism of exertional syncope in patients with aortic stenosis. The predominant left ventricular inferior-wall myocardial ischaemia in our patient might be an additional stimulus to left ventricular mechanoreceptors, resulting in a profound cardio-inhibitory response.