Practical optimisation of antiarrhythmic drug therapy using pharmacokinetic principles.

The optimisation of antiarrhythmic drug therapy is dependent on the definitions and methods of short term efficacy testing and the characteristics of those drugs used for rhythm disturbances. The choice of an initial antiarrhythmic drug dosage is highly empirical, and will remain so until the measurement of free concentrations, enantiomeric fractions and genetic phenotyping becomes routine. However, the clinician can devise an efficient initial dosage for efficacy testing procedures based on pharmacokinetic principles and disposition variables in the literature.

Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects.

To evaluate the effects of calcium pretreatment on the disposition and electrocardiographic effects of verapamil, 8 healthy male volunteers received treatment in each of 3 phases in a randomized, double-blind, crossover manner. Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride followed by 4 ml of 0.

Flow cytometric measurement of rRNA levels detected by fluorescent in situ hybridization in differentiating K-562 cells.

The flow cytometric detection of fluorescent in situ hybridization (FISH) performed on intact cells in suspension is a recently described method (Bauman et al. 1989). We studied the application of this method for monitoring cellular differentiation.

Long-term follow-up in patients with incessant ventricular tachycardia.

Seventeen patients with coronary artery disease, idiopathic dilated cardiomyopathy or no organic heart disease who presented with incessant ventricular tachycardia (VT) were studied and followed for a mean period of 51 +/- 35 months. In these patients the incessant VT included greater than or equal to 3 episodes of sustained VT at a rate of greater than or equal to 120 beats/min and frequent episodes of nonsustained VT over a 24-hour period. No patient had electrolyte disorder, prolonged QT interval, drug-induced arrhythmia or myocardial infarction less than 2 weeks old.

The use of E. coli exonuclease III to generate single stranded DNA in BrdUrd cell-cycle analysis permits simultaneous detection of cell surface antigens.

An immunocytochemical method for the simultaneous flow cytometric quantitation of total cellular DNA, incorporated 5-bromo-2'-deoxyuridine (BrdUrd) and one or more cell surface antigens has been developed. Biotin labeling of cell surface antigens, critically tuned fixation techniques and an enzymatic denaturation of cellular DNA are the essential features of this method. Enzymatic denaturation of cellular DNA was shown to prevent loss of cell surface antigen-bound biotin moieties, and thus to preserve cell surface immunofluorescence distribution.

Confocal microscopy as a tool for the study of the intranuclear topography of chromosomes.

A scanning confocal microscope was used to investigate the spatial positions of specific regions within blood cell nuclei. These centromeric regions were fluorescently labelled by in-situ hybridization to suspended nuclei with a centromere-1-specific DNA probe. The 3-D image data sets, obtained by optical sectioning of the cells, were used to determine the spatial position of the centromeric regions in the nuclei by means of specially developed software.

The predictive value of electrophysiologic studies in untreated patients with Wolff-Parkinson-White syndrome.

The ability of invasive electrophysiologic studies to predict future arrhythmic events in patients with minimally symptomatic Wolff-Parkinson-White syndrome is not known. To assess this ability, 42 patients with evidence of atrioventricular (AV) pre-excitation on the surface electrocardiogram underwent electrophysiologic studies and were then followed up as outpatients taking no medications. The patients were classified into three groups on the basis of prestudy symptoms: group I, 15 asymptomatic patients; group II, 10 patients with infrequent symptoms but no documented arrhythmias; and group III, 17 patients with one documented episode of supraventricular tachycardia or atrial fibrillation, or both.

Detection of neutrophil-activating peptide NAP/IL-8 and NAP/IL-8 mRNA in human recombinant IL-1 alpha- and human recombinant tumor necrosis factor-alpha-stimulated human dermal fibroblasts. An immunocytochemical and fluorescent in situ hybridization study.

A neutrophil-activating peptide (NAP)/IL-8 produced by LPS-stimulated human peripheral blood monocytes was biochemically purified and functionally characterized by different investigators. Work conducted in our laboratory showed that NAP/IL-8 as well as variants of this peptide are produced by a variety of cells (e.g.

Three-dimensional reconstruction of pericentromeric (1q12) DNA and ribosomal RNA sequences in HL60 cells after double-target in situ hybridization and confocal microscopy.

A fluorescent in situ hybridization procedure was applied to simultaneously label intranuclear pericentromeric (1q12) sequences of the chromosomes 1 and cytoplasmic ribosomal RNA sequences in whole cells of the promyelocytic HL60 cell line. For this purpose biotinated chromosome 1-specific (1q12) repetitive satellite DNA and 28S ribosomal ssRNA probes were used. The entire procedure was performed in suspension to preserve nuclear morphology.

Spatial topography of a pericentromeric region (1q12) in hemopoietic cells studied by in situ hybridization and confocal microscopy.

A fluorescent in situ hybridization procedure with a chromosome 1-specific (1q12) repetitive satellite DNA probe was used to label the 1q12 regions of the chromosomes 1 in spherical and polymorphic hemopoietic cell nuclei. The entire procedure was performed in suspension to preserve nuclear morphology. The result was studied by three-dimensional analysis, as provided by a scanning laser confocal microscope.

Flow cytometric quantification of human chromosome specific repetitive DNA sequences by single and bicolor fluorescent in situ hybridization to lymphocyte interphase nuclei.

Fluorescent in situ hybridization allows for rapid and precise detection of specific nucleic acid sequences in interphase and metaphase cells. We applied fluorescent in situ hybridization to human lymphocyte interphase nuclei in suspension to determine differences in amounts of chromosome specific target sequences amongst individuals by dual beam flow cytometry. Biotinylated chromosome 1 and Y specific repetitive satellite DNA probes were used to measure chromosome 1 and Y polymorphism amongst eight healthy volunteers.

Flow cytometric detection of beta-globin mRNA in murine haemopoietic tissues using fluorescent in situ hybridization.

The novel method for flow cytometric detection of cellular RNA species in suspended cells by fluorescent in situ hybridization (FC-FISH) was applied in the evaluation of beta-globin expression in murine haemopoietic tissues. Normal murine bone marrow cells and regenerating bone marrow cells obtained after lethal irradiation and bone marrow transplantation as well as murine 15 d fetal liver were examined. Furthermore, spleens and bone marrow of phenylhydrazine-induced anaemic mice were studied.

Fluorescent in-situ hybridization to detect cellular RNA by flow cytometry and confocal microscopy.

A fluorescent in-situ hybridization procedure was developed which is suitable for detection of specific cellular RNA in cells fixed in suspension. The procedure was originally developed for analysis of single-cell suspensions by flow cytometry. The resulting fluorescent cells proved to have their 3-D morphology perfectly preserved.

Motor vehicles as a site of accidental poisonings.

Although most poisonings occur within the home, the toxic agents involved are customarily transported there by motor vehicles. Over a 9-month period, all potentially toxic exposures reported to a poison information center that occurred in a motor vehicle were collected. Common toxins were identified and associated incidence and risk were assessed; 68% were pediatric exposures and the remainder were in adults.

Detection of host cells following sex-mismatched bone marrow transplantation by fluorescent in situ hybridization with a Y-chromosome specific probe.

Fluorescent in situ hybridization (FISH) with a biotinylated Y-chromosome specific repetitive DNA probe was applied to detect Y-bearing cells in blood and bone marrow samples from patients with hemopoietic malignancies after a sex-mismatched bone marrow transplantation. The sensitivity of this method is in the order of 0.1% Y-bearing nuclei in male recipients transplanted with female marrow.

Effect of physician characteristics on the cesarean birth rate.

The rising cesarean birth rate has become of increasing concern to the obstetric profession and the public. There is a general consensus that the major obstetric indications responsible for the rising rate are dystocia, fetal distress, breech presentation, and previous cesarean delivery. However, the role of sociologic or nonmedical factors has not been established.

Propafenone: a novel type Ic antiarrhythmic agent.

Propafenone is an investigational type Ic anti-arrhythmic agent that markedly slows conduction velocity in all cardiac tissues. Propafenone also possesses weak beta- and calcium-channel blocking properties. The bioavailability of propafenone is dose-dependent.

Cryothermal mapping of the sinus node in dogs: a simple method of localising dominant and latent pacemakers.

To investigate the potential use of cryothermal mapping to localise the sites of the dominant and latent pacemakers of the sinus node, we compared the results of cryothermal and electrical mapping of the sinus node in 16 dogs. In all dogs, cooling (-5 to +5 degrees C) of a localised epicardial area of about 3 X 3 mm2 close to the sulcus terminalis (area 1) resulted in a decrease in heart rate and a change in the P wave configuration. Cooling of an additional area of up to 15 X 3 mm2 (area 2) while cooling of area 1 was maintained resulted in a further decrease in heart rate and a further change in P wave configuration until junctional rhythm occurred.

Intrahepatic cholangiographic abnormalities in liver transplants: correlation with biopsy evidence of rejection and other disorders.

We investigated the cholangiographic appearance of intrahepatic bile ducts in 56 liver transplants and correlated the findings with biopsy evidence of acute rejection and other histologic diagnoses. Mild to moderate narrowing, stretching, separation, and poor filling of the bile ducts were common. Narrowing was present in 69 (92%) of 75 studies and was at least moderate in degree in 14 (19%).