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Biomedical subjects

T Annesley

Publications and source records attributed to T Annesley.

14 recordsLinked to original sources

Liquid chromatographic analysis of mexiletine in serum, with alternate application to tocainide, procainamide, and N-acetylprocainamide.

A simple and precise high performance liquid chromatographic method for the determination of mexiletine in human serum or plasma is described. Following addition of N-propionylprocainamide as internal standard the specimens are extracted, under basic conditions, into methylene chloride. After removal of the aqueous layer the drug is back-extracted into dilute acid, which is then injected directly for analysis. The extraction efficiency is 79% for both mexiletine and internal standard, and the assay is linear to 4 mg/L (twice upper therapeutic concentration). Inter-run coefficients of variation are 3.0% or less. The relative retention time of mexiletine to internal standard averages 1.3. An adaptation of this method is described for an alternate application to the analysis of tocainide, procainamide and N-acetylprocainamide.

Acecainide↗

Pharmacodynamics of intravenous procainamide as used during acute electropharmacologic testing.

No previous studies have determined the pharmaco-dynamics of intravenous procainamide when administered in a dose of 15 mg/kg and at a rate of 50 mg/min, as is common practice during electropharmacologic testing. In this study, 30 patients received procainamide in this fashion; the right ventricular effective refractory period and the QRS duration at a ventricular pacing rate of 120/minute were then determined every minute for 20 minutes. Ten patients received no maintenance infusion of procainamide (group A), 10 received a 4 mg/min maintenance infusion (group B) and 10 received an 8 mg/min maintenance infusion (group C). Ten additional patients received no procainamide and served as control subjects (group D). The plasma procainamide concentration was measured at 1, 5, 10, 15 and 20 minutes after the loading dose was administered. A stable plasma procainamide concentration was not present in group A, B, or C until 15 minutes after infusion of the loading dose. The effective refractory period and QRS duration increased compared with baseline at 1 minute, decreased between 1 and 10 minutes and then remained essentially unchanged between 10 and 20 minutes in all 3 treatment groups. Concentration-effect relation was linear in each treatment group. The plasma procainamide concentrations in group C were significantly greater than in group A; however, the effects on refractoriness and QRS duration were similar in both groups. These findings indicate that with a procainamide dosing method commonly used during electropharmacologic testing, the plasma procainamide concentration decreases significantly during the first 15 minutes after the loading dose is administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Significance of ST segment depression during paroxysmal supraventricular tachycardia.

During paroxysmal supraventricular tachycardia, patients frequently experience chest pain and marked ST segment depression suggesting acute myocardial ischemia. The purpose of this study was to assess whether ST depression during supraventricular tachycardia is caused by myocardial ischemia as reflected by net myocardial lactate production. Twenty-five patients (14 men, 11 women) who had a history of paroxysmal supraventricular tachycardia and a mean age (+/- SD) of 38 +/- 14 years underwent electrophysiologic testing. Twenty-four of these patients had no evidence of coronary disease, whereas one patient had undergone previous coronary bypass surgery. Nineteen patients had orthodromic and six patients had atrioventricular node reentrant tachycardias. A 12 lead electrocardiogram and simultaneous femoral artery and coronary sinus blood samples for lactate determinations were obtained at baseline and at 5 and 10 min of supraventricular tachycardia. Mean baseline heart rate of 83 +/- 12 beats/min increased to 180 +/- 25 beats/min during supraventricular tachycardia. All patients had 1 to 8 mm of ST segment depression in 1 to 9 of the 12 leads. Chest pain occurred in 64% of patients during supraventricular tachycardia. Baseline myocardial lactate extraction was 28 +/- 13% with no significant change at 5 or 10 min of tachycardia. In contrast, in a comparison group of seven patients with known coronary artery disease, atrial pacing at 168 +/- 26 beats/min in five patients resulted in greater than or equal to 1 mm ST depression in 2 to 7 of the 12 leads and a change in lactate extraction from a baseline of 29 +/- 13% to -27 +/- 20% (p less than 0.05) indicating net myocardial lactate production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of chronic amiodarone therapy on ventricular tachycardia induced by programmed ventricular stimulation.

Several studies have reported upon the inducibility of ventricular tachycardia (VT) with programmed ventricular stimulation (PVS) during chronic amiodarone therapy; however, few studies have systematically described and compared the morphology, duration, and cycle length of VT induced by PVS before and after amiodarone. In this study, 26 patients with symptomatic VT or ventricular fibrillation were evaluated by PVS by means of one to three extrastimuli (ES) before treatment and after 2 months of amiodarone therapy. Before amiodarone, sustained unimorphic VT was induced in 21 patients (group A) and symptomatic, nonsustained VT was induced in five patients (group B). After 65 +/- 8 days of amiodarone (total dose 64.5 +/- 8.9 gm, mean +/- S.D.), 15 of 21 patients (71%) in group A had sustained VT, five patients (24%) had nonsustained VT, and one patient had no VT induced. Four of five patients (80%) in group B had sustained VT and one patient had no VT induced. VT was induced by the same or by fewer number of ES in 79% of cases. When the morphologies of the VT induced before and after amiodarone were compared, the morphology of VT induced after amiodarone was the same in only 8 of 24 patients (33%), unimorphic but different in 14 patients (58%), and polymorphic in the remaining two patients. No correlation was found between the serum concentrations of amiodarone, desethylamiodarone, tetraiodothyronine, triiodothyronine, or reverse triiodothyronine, and similarities or differences in VT morphology, VT cycle length, or the relative number of ES required to induce VT after treatment with amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Interrelationships between serum levels of amiodarone, desethylamiodarone, reverse T3 and the QT interval during long-term amiodarone treatment.

The interrelationships between serum levels of amiodarone, desethylamiodarone, and reverse T3, and changes in the corrected QT interval (delta QTc) were examined in 22 patients during long-term treatment with amiodarone. At 1, 3, and 6 months of follow-up, the correlation coefficient between serum levels of amiodarone or desethylamiodarone and reverse T3 ranged from 0.01 to -0.2 (p greater than 0.4). At the same time intervals, the correlation coefficient between both amiodarone and desethylamiodarone levels and delta QTc ranged from 0.1 to -0.1 (p greater than 0.6), and the correlation coefficient between reverse T3 and delta QTc also ranged between 0.1 to -0.1 (p greater than 0.5). Substituting percent delta QTc for delta QTc also did not reveal a significant correlation. These data demonstrate that serum levels of reverse T3 cannot be used as a substitute for serum levels of amiodarone in monitoring patients being treated with amiodarone. The absence of a correlation between serum reverse T3 levels and delta QTc suggests that the delay in repolarization which occurs during amiodarone therapy is not secondary to an amiodarone-induced abnormality in thyroid hormone metabolism.

Adult↗

A high performance liquid chromatographic assay for tocainide with alternate application for the determination of lidocaine, procainamide, and N-acetylprocainamide.

We describe a simple, isocratic high-performance liquid chromatographic method for measuring the oral antiarrhythmic agent tocainide in serum. The extraction requires 200 microliters of serum, is performed on a reverse-phase column, and utilizes the drug mepivacaine as the internal standard. This analytical method can also be used to assay procainamide, n-acetylprocainamide, or lidocaine with minor modifications to either the extraction protocol or the wavelength used to monitor column eluant.

Acecainide↗

Topical application of isotretinoin gel improves oral lichen planus. A double-blind study.

In a double-blind study, 20 patients with oral lichen planus were treated twice daily with 0.1% isotretinoin gel or the vehicle alone for two months. Subsequently, patients who used the placebo received the active preparation for another two months. Patients treated with the active medication displayed significantly greater improvement than patients receiving the placebo. Patients who were treated initially with the placebo showed statistically significant improvement after receiving the topical isotretinoin treatment for two months. Side effects from using the gel were primarily a transient burning sensation or irritation on initial application.

Administration, Topical↗

Liquid-chromatographic analysis for cyclosporine with use of a microbore column and small sample volume.

This liquid-chromatographic assay requires 0.2 to 0.5 mL of whole blood, avoids the use of diethyl ether, and consumes only 10 to 20% of the solvents used in prior methods. Sample preparation involves an acidic extraction with methyl-t-butyl ether, performed in a 13 X 100 mm disposable glass tube, then a short second extraction of the organic phase with sodium hydroxide. After evaporation of the methyl-t-butyl ether, chromatography is performed on an "Astec" 2.0-mm (i.d.) octyl column. We compared results by this procedure with those by use of earlier larger-scale extractions and their respective 4.6-mm (i.d.) columns; analytical recoveries of cyclosporins A and D were comparable with previous findings and results for patients' specimens were equivalent, but the microbore columns provided greatly increased resolution and sensitivity.

Chromatography, Liquid↗

Simultaneous determination of penicillin and cephalosporin antibiotics in serum by gradient liquid chromatography.

We describe a "high-performance" liquid-chromatographic method for simultaneously measuring various penicillin and cephalosporin antibiotics. After extraction from serum, which in general is quantitative, the drugs are separated by use of a "Bondapak phenyl" column and a gradient mobile phase. For these drugs retention times depend on the pH of the mobile phase; we present retention times under selected pH conditions.

Anti-Bacterial Agents↗

Occupational cadmium exposure and renal status.

With chronic low-level exposure to cadmium (Cd) the kidney is considered to be the organ at risk. Thus, permissible exposure levels (PEL) should be established to protect against the risk of renal dysfunction for a working lifetime. In this study, the prevalence of renal dysfunction among 33 male subjects exposed to Cd fumes at and below the current PEL of 100 microgramsCd/m3 for at least 21 years, was 21% (adjusted for confounding factors). The average cumulative time-weighted exposure in subjects with abnormal renal function was 1137 micrograms/m3 years, which was significantly different (p = .02) from subjects with normal renal function. These findings are consistent with those of other investigators and suggest that the current PEL does not protect against the risk of renal dysfunction, secondary to Cd fume exposure, for a working lifetime (approximately equal to 40 years).

Adult↗

Myocardial involvement in polymyositis.

Polymyositis (PM) is a myopathic syndrome that results in pathology believed to be primarily confined to skeletal muscle. Several recent reports, based on quantitative determinations of total serum creatine kinase (CK) and MB isoenzyme activity, accepted serologic correlates of active myocardial injury, suggest that cardiac involvement in PM may occur more frequently than has been clinically appreciated. We retrospectively studied 12 patients with PM; 83% (10) were found to have substantial elevations in CK-MB activity, often to levels exceeding those seen with myocardial infarctions, thus confirming a high probability of myocardial involvement in PM. Failure to detect this clinically may be indicative of the insensitivity of current technology. A review of the literature substantiates the importance of appreciating the spectrum, frequency and functional consequences (i.e., conduction disturbances, cardiomyopathy) of myocardial involvement in PM.

Cardiomyopathies↗

Protein excretion patterns in cadmium-exposed individuals: high resolution electrophoresis.

High resolution electrophoresis was used to evaluate protein excretion patterns in six cadmium-exposed individuals with proteinuria, seven subjects with nonspecific nephropathies, and four normal unexposed subjects. The aim of the investigation was to determine (a) the type of excretion pattern (i.e., glomerular, tubular, or mixed) associated with cadmium exposure and (b) if the pattern in the cadmium-exposed individuals was distinctly different from subjects with nonspecific nephropathies. The electrophoretic results were consistent with the quantitative results for the cadmium-exposed workers. The results suggest that the pattern associated with cadmium exposure can be glomerular or mixed and that it is different (i.e., no gamma band) from nonspecific nephropathies.

Adult↗