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Biomedical subjects

J T Stewart

Publications and source records attributed to J T Stewart.

At least 19 recordsLinked to original sources

High-performance liquid chromatographic analysis of pindolol enantiomers in human serum and urine using a reversed-phase cellulose-based chiral column.

Simple, sensitive and reliable high-performance liquid chromatographic methods are reported for the determination of pindolol enantiomers in human serum and urine. The methods involved a solid-phase extraction of serum and a direct injection of urine samples. The separation of R(+)- and S(-)-pindolol was accomplished on a reversed-phase cellulose-based chiral column with a mobile phase of 40:60 (v/v) acetonitrile-0.3 M aqueous sodium perchlorate at a flow-rate of 0.5 ml/min. The detection was achieved by monitoring the fluorescence emission of pindolol enantiomers at 310 nm with excitation at 270 nm. The limits of detection were 1.2 ng/ml of R(+)- and 4.3 ng/ml of S(-)-pindolol in serum, and 21 ng/ml of R(+)- and 76 ng/ml of S(-)-pindolol in urine. The external standard method was used for quantitation. The methods have been applied to the analysis of human serum and urine samples in a pharmacokinetic study.

Adrenergic beta-Antagonists

Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and lactate levels during left anterior descending coronary artery angioplasty.

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary

A supercritical fluid chromatographic method using packed columns for phenylbutazone and oxyphenbutazone in serum, and for phenylbutazone in a dosage form.

The separation of phenylbutazone (PB) and its major metabolite oxyphenbutazone (OPB) using supercritical fluid chromatography (SFC) has been investigated. The separations were studied on octadecylsilane, silica and cyano packed columns with 5% methanol in carbon dioxide as mobile phase and detection at 240 nm. The octadecylsilane column showed the most favourable chromatographic parameters for the analysis of the analytes. Recoveries of PB and OPB from spiked human serum were in the 82-83% range using solid phase extraction on an ODS cartridge. Limits of detection of the SFC assay were 0.1 microgram ml-1 for PB and 1.0 microgram ml-1 for OPB. Accuracy and precision of the method were in the 0.24-4.94% range for PB and OPB. The SFC method was directly comparable to an HPLC assay of the same analytes. The SFC method was also applied to a commercial 100 mg dosage form of PB with good recovery of PB.

Capsules

Management of behavior problems in the demented patient.

Behavior problems are common in persons with dementia and often lead to caregiver stress and institutionalization for the patient. In most cases, however, these problems are amenable to treatment. Although drug therapy may be necessary to manage some behavior problems, nonpharmacologic strategies may work as well, if not better, with fewer adverse effects. Support and education for the patient's family are the cornerstone of management. At some point, most demented patients display agitation. Appropriate, often nonpharmacologic management of agitation may include establishing a "no-fail" environment, limiting goals and providing reassurance. While delusions and hallucinations are also common, they seldom lead to agitation. Sleep disturbance and wandering are particularly upsetting to the patient's family, but these problems often respond to nonpharmacologic strategies, such as restricting naps and providing more cues about time and place. Depression, which occurs in many demented patients, is an especially treatable cause of disability.

Alzheimer Disease

High-performance thin-layer chromatographic determination of digoxin and related compounds, digoxigenin bisdigitoxoside and gitoxin, in digoxin drug substance and tablets.

A high-performance thin-layer chromatographic (HPTLC) method for the determination of digoxin and its related compounds digoxigenin bisdigitoxoside (DBD) and gitoxin in digoxin drug substance and tablets was developed. Separation of the three compounds was accomplished on a C18 wettable reversed-phase plate using water-methanol-ethyl acetate (50:48:2, v/v/v) as the mobile phase. The analytes were determined by densitometry using absorbance for digoxin and fluorescence for the two related compounds. All peaks were quantified by peak-height analysis. Linear regression analysis of the data was performed for all three compounds. The calibration range for digoxin was set at 320-480 ng per 5-mm band, equivalent to 80-120% (w/w) of a 400-ng band load, that for DBD was set at 4-12 ng per 5-mm band, equivalent to 1-3% (w/w) of the digoxin load, and that for gitoxin was set at 0.4-1.6 ng per 5-mm band, equivalent to 0.1-0.4% (w/w) of the digoxin load. The limit of quantification (LOQ) for digoxin was 64 ng per 5-mm band with a limit of detection (LOD) of 8 ng per 5-mm band. The LOQs for both DBD and gitoxin were 0.12 ng per 5-mm band with LODs of 0.4 ng per 5-mm band. The linearity range for the digoxin peak height in the absorbance mode was 0-5000 ng per 5-mm band. The linearity range for DBD and gitoxin peak heights in the fluorescence mode was 0-2000 ng per 5-mm band.

Carbohydrate Sequence

Management of arrhythmias in hypertrophic cardiomyopathy.

In the management of hypertrophic cardiomyopathy the goals should be the control of symptoms, and the identification and treatment of those at high risk. Arrhythmias, particularly atrial fibrillation and nonsustained ventricular tachycardia, are common in adult patients with hypertrophic cardiomyopathy. Atrial fibrillation has long been thought to herald an ominous prognosis, but this is probably not the case, and in the majority of patients atrial fibrillation can be controlled without accelerated symptomatic deterioration. Uncontrolled observations indicate that low-dose amiodarone may be the most useful drug in both paroxysmal and chronic atrial fibrillation. The detection of nonsustained ventricular tachycardia on ambulatory ECG monitoring remains the single most useful indicator of the risk of sudden death in the adult patient, and the treatment of choice is again low-dose amiodarone. The mechanism of sudden death, and the mode of action of amiodarone in preventing it, are not known for certain in the majority of patients. The risk of sudden death is higher in children and adolescents, but arrhythmias are less common, and no useful predictive marker of increased risk has been found. The roles of invasive electrophysiological studies and the implantable cardioverter-defibrillator are still being evaluated.

Arrhythmias, Cardiac

Chromatographic analysis of selected tetracyclines from dosage forms and bulk drug substance using polymeric columns with acidic mobile phases.

The LC analysis of selected tetracyclines from dosage forms and bulk drug substance using polymeric columns has been studied. Mobile phases containing acetonitrile-0.02 M sodium perchlorate (pH 2.0) were used. The tetracyclines were detected by their absorbance at 280 nm. The columns included: a polystyrene-divinylbenzene (PS-DVB) column and a polymethacrylate column with octadecyl ligands (PM-C18). Performance of the two columns was compared and applicability of the described methods for compendial use has been evaluated. The tetracyclines investigated include: minocycline, oxytetracycline, tetracycline, demeclocycline, chlortetracycline, methacycline, doxycycline and meclocycline.

Acetonitriles

Stability of cefmetazole-doxycycline mixtures in sodium chloride and dextrose injections.

This study involved the mixing of cefmetazole 1 and 2 Gm with doxycycline 100 and 200 mg, in sodium chloride and dextrose injections. The mixtures were stored either at ambient temperature for 96 h or at 4 degrees C for 168 h followed by 8 h at ambient temperature. HPLC assay of both cefmetazole and doxycycline levels were performed at prescribed sampling times. Cefmetazole 1 Gm in doxycycline 100 and 200 mg mixtures, in sodium chloride injection was not stable up to 4 h, but cefmetazole 2 Gm in doxycycline 100 and 200 mg mixtures, in sodium chloride injection was stable for up to 24 h. The cefmetazole controls were stable for 72 h in sodium chloride injection. Cefmetazole 1 Gm with doxycycline 100 mg, in dextrose injection was stable up to 72 h. The 2 Gm cefmetazole and 100 mg doxycycline mixture in dextrose injection was stable for 96 h. Cefmetazole 1 Gm and doxycycline 200 mg in dextrose injection was stable up to 96 h, but the 2 Gm cefmetazole-200 mg doxycycline mixture was only stable for 72 h. Cefmetazole controls in dextrose injection were stable for 24 h. Doxycycline 100 and 200 mg were stable with cefmetazole 1 and 2 Gm, in both sodium chloride and dextrose injections for 96 h at ambient temperature. Doxycycline control solutions were also stable for 96 h. Cefmetazole 1 and 2 Gm and doxycycline 100 and 200 mg were generally stable in both sodium chloride and dextrose injections at 4 degrees C for 168 h, and at ambient temperature for 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefmetazole

High-performance liquid chromatographic separation of ondansetron enantiomers in serum using a cellulose-derivatized stationary phase and solid-phase extraction.

R(-)-Ondansetron and S(+)-ondansetron in human serum were resolved and quantified using a stereospecific HPLC method. Each enantiomer and the internal standard prazosin were isolated from serum using a solid-phase extraction procedure on a cyanopropyl column. Recoveries of 97, 96 and 88% were obtained for the R(-)-enantiomer, the S(+)-enantiomer, and the internal standard, respectively. A cellulose-based chiral analytical column (Chiralcel OD) was used with a mobile phase consisting of hexane-95% ethanol-2-propanol-acetonitrile (65:25:10:1, v/v). Linear calibration curves were obtained for each enantiomer in serum in the concentration range 10-200 ng/ml. The limit of quantitation of each enantiomer was 10 ng/ml. The detection limit for each enantiomer in serum using UV detection at 216 nm was 2.5 ng/ml (signal-to-noise ratio of 3).

Cellulose

Separation of tetracyclines by liquid chromatography with acidic mobile phases and polymeric columns.

The LC separation of selected tetracyclines has been studied using polymeric columns. Mobile phases containing acetonitrile-0.02 M sodium perchlorate, pH 2.0, were used. Asymmetry factor and number of theoretical plates were calculated for the tetracyclines investigated on four polymeric columns. The columns included: two polystyrene-divinylbenzene (PS-DVB) copolymeric columns, a PS-DVB column with octadecyl ligands and a polymethacrylate column with octadecyl ligands (PM-C18). The PLRP-S (PS-DVB) column and the PM-C18 column were found to be the most suitable for the analysis of the selected tetracyclines. Resolutions between pairs of selected tetracyclines were calculated and compared for the latter two columns, with the PLRP-S (PS-DVB) columns showing the best results. The PM-C18 column has the advantage of allowing the use of higher flow rates, which minimized analysis times. The tetracyclines included minocycline, oxytetracycline, tetracycline, demeclocycline, chlortetracycline, methacycline, doxycycline and meclocycline. Representative degradation products and impurities for selected tetracyclines were also included.

Chromatography, High Pressure Liquid

Left ventricular energetics: heat production by the human heart.

OBJECTIVE: The aim was to examine the effect of coronary artery disease on human left ventricular energetics by a comparison of left ventricular oxygen consumption and heat production. The usefulness of measurement of left ventricular heat production for the detection of the expected change in left ventricular energetics produced by atrial pacing to a faster heart rate was also assessed. METHODS: Forty six patients (mean age 57 years; 31 men) undergoing cardiac catheterisation and coronary arteriography for the investigation of chest pain were studied. Normal left ventricular function and normal coronary arteries were present in eight and 38 had atheromatous coronary artery disease. Left ventricular heat production was calculated from coronary blood flow, the coronary arteriovenous (aorta-coronary sinus) temperature difference, and the areas under thermodilution curves recorded in the aorta and coronary sinus after injection of cold saline into the pulmonary artery. Mean external left ventricular power was calculated from mean arterial blood pressure and cardiac output. Left ventricular mechanical efficiency was derived from heat production and the energy value of myocardial oxygen use, assuming aerobic metabolism. In 27 patients studies were repeated during atrial pacing from the coronary sinus. RESULTS: At rest under basal conditions left ventricular heat production was 2.4(SD 1.0) W in patients with normal hearts and 3.1(1.4) W in patients with coronary disease (NS). Mechanical efficiency was 44.2(9.7)% in the normal patients and 30.7(10.9)% in those with coronary disease (p = 0.003). During atrial pacing to a faster heart rate left ventricular energy supply increased from 4.6(2.7) W to 5.9(3.3) W (p < 0.0005), and heat production increased from 3.0(1.6) W to 4.6(2.4) W (p < 0.0005), but mean external power was not altered. As the extra energy used during pacing was "wasted" as heat, there was a significant fall in left ventricular mechanical efficiency with pacing from 33.9(13.5)% to 18.9(15.2)% (p < 0.0005). CONCLUSIONS: These results show the effect of coronary artery disease on the energetics of left ventricular function. They also show that the method and equipment can detect the expected alteration in left ventricular energetics produced by atrial pacing. The measurement of left ventricular heat production and oxygen consumption allows assessment of the total left ventricular energy flux, and may be useful for the evaluation of drug treatment with such as inotropes and vasodilators, and for the investigation of the functional consequences of left ventricular disease.

Adult

Case management in Alzheimer's disease.

Patients with a diagnosis of Alzheimer's disease and their families need the assistance of a case manager to deal with the issues of long-term care. The case manager assists with education, planning, linking to formal and informal resources, and addressing emotional needs in the family unit. This article discusses specific suggestions to address problems in the three stages of Alzheimer's disease from the time of medical diagnosis to the end of life.

Alzheimer Disease