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Biomedical subjects

L M Shaw

Publications and source records attributed to L M Shaw.

At least 145 records · Page 8Linked to original sources

Factors affecting the binding of disopyramide to serum proteins.

We investigated the influence of the following factors on the binding of disopyramide to serum proteins: method of drug quantification [enzyme immunoassay (EMIT) compared with liquid chromatography (HPLC)], separation technique (ultrafiltration vs equilibrium dialysis), temperature, pH, and total concentration of disopyramide. EMIT and HPLC measurements of disopyramide in ultrafiltrates prepared from 50 sera agreed well: EMIT = 1.046 HPLC + 0.042, (r = 0.928, SEE = 0.04 mg/L). Free disopyramide concentrations in ultrafiltrates of dialyzed sera were similar to those measured in the corresponding dialysates by the EMIT method for 30 patients' sera: ultrafiltrate of serum retentate = 1.053 dialysate + 0.042. Concentrations of free [14C]disopyramide were little affected by temperature. The concentration of free disopyramide decreased as the pH was increased from 7.0 to 7.8. The concentration of free disopyramide, as determined by ultrafiltration, is strongly and directly related to total drug concentration. In the sera of 50 cardiac patients receiving chronic therapy with disopyramide and with total disopyramide concentrations of 0.5 to 5.8 mg/L, the proportion of free disopyramide ranged from 16 to 54%.

Blood Proteins↗

The effect of lidocaine infusion on the ventilatory response to hypoxia.

The authors studied the effect of lidocaine infusion on the ventilatory response to isocapnic hypoxia in nine healthy male subjects. Lidocaine infusion (serum concentration 3.6 +/- 0.1 micrograms/ml) was associated with a decrease in the shape factor, "A," of the hypoxic ventilatory response in eight of our nine subjects (P less than 0.02). Overall, "A" decreased from 419 +/- 102 1 . min-1 . mmHg before lidocaine to 335 +/- 77 1 . min-1 . mmHg during lidocaine infusion (mean +/- SEM, N = 9). The authors conclude that despite significant intersubject variability, clinically useful serum lidocaine concentrations depress hypoxic ventilatory drive. Patients with carbon dioxide retention, whose resting ventilation depends on hypoxic drive, may be at risk of ventilatory failure when lidocaine is administered for arrhythmia control or regional anesthesia.

Adult↗

Development of a stable reference material for prostatic acid phosphatase.

We describe the development of a stable reference material for prostatic acid phosphatase, derived from human prostatic tissue and human seminal fluid. The enzyme was purified by an L-tartramic acid affinity-chromatography technique. Two-dimensional electrophoresis revealed essentially no contaminating proteins, and specific tests revealed no contaminating enzymes. The preparations, in a matrix containing 30 g of human serum albumin and 0.1 mol of sodium acetate per liter, pH 6.0, were studied with respect to stability of both catalytic activity and immunological identity. We conclude that the preparations from either source are satisfactorily stable, and that either is acceptable for use in preparing clinical reference materials. These materials will be used in developing a reference method.

Acid Phosphatase↗

The effect of lidocaine on the ventilatory response to carbon dioxide.

The authors determined the effect of intravenous lidocaine, both as a bolus and as an infusion, on the ventilatory response to CO2. Bolus injection of 1.5 mg/kg lidocaine caused a decrease in the slope of the CO2 ventilatory response curve from 2.66 +/- 0.30 (mean +/- SEM) to 1.31 +/- 0.44 1 X min-1 X mmHg-1 within 90 s; the effect was transient, with slope returning to 2.39 +/- 0.83 1 X min-1 X mmHg-1 150 s after injection. The transient, subconvulsive lidocaine concentrations present during ventilatory depression (8.9 +/- 2.0 micrograms/ml) may be sufficient to desensitize the medullary ventilatory control centers. Lidocaine infusion at the rate of 60 micrograms X kg-1 X min-1 (serum lidocaine concentrations of 3.5 +/- 0.2 micrograms/ml) increased the slope of steady state CO2 response curves from 2.89 +/- 0.29 to 4.17 +/- 0.44 1 X min-1 X mmHg-1 (P less than 0.05); with discontinuation of the infusion, slope returned to 3.18 +/- 0.33 1 X min-1 X mmHg-1 (P less than 0.05). The authors conclude that bolus injection of lidocaine transiently can depress ventilatory control, however, rapid redistribution of lidocaine makes this a transient phenomenon that can be treated with supplemental oxygen if necessary. The increased CO2 sensitivity observed during lidocaine infusion suggests that studies of ventilatory control in patients receiving conduction anesthetics must take into account the direct effect of absorbed anesthetics on ventilatory control.

Adult↗

Imperforate hymen and vaginal atresia and their associated anomalies.

The presenting features and associated abnormalities of imperforate hymen and vaginal atresia were studied in 24 girls under the age of 16 years. Hydrocolpos or hydrometrocolpos occurred in 8 infants, 13 older girls developed haematocolpos, but 3 of the girls had no distension of the genital tract. Seven of the older girls were diagnosed as having appendicitis. Anorectal anomalies were present in 9 of the children. Intravenous pyelography was performed on 16 girls and was normal in only one. Urinary tract investigations are indicated in all girls with vaginal outlet obstruction, and the vaginal orifice should be inspected in all girls with anorectal abnormalities.

Adolescent↗

Electrophysiologic study for ventricular arrhythmia: effect on total and myocardial-specific creatine kinase activity.

To determine the potential for myocardial injury during electrophysiologic study for ventricular arrhythmia, total creatine kinase and creatine kinase B-subunit enzyme activity were serially measured after the procedure in 24 patients. During electrophysiologic study 14 of the 24 patients had sustained ventricular tachycardia or fibrillation, 4 patients had nonsustained ventricular tachycardia, and 6 patients had no ventricular arrhythmia induced. Cardioversion was necessary because of hemodynamic collapse in 9 of the 14 patients with sustained ventricular tachycardia or ventricular fibrillation. Coronary heart disease was present in 14 of the 24 patients, in 9 of the 14 with sustained ventricular tachycardia or ventricular fibrillation, and in 7 of the 9 patients requiring cardioversion. Total creatine kinase was modestly elevated (greater than twice baseline or greater than normal, or both) 24 hours after electrophysiologic study in 10 (42%) of the patients. Electrophysiologic study with or without the induction of ventricular tachycardia or ventricular fibrillation was not associated with increased creatine kinase B-subunit activity even in patients with coronary heart disease.

Adolescent↗

Treating GI reflux with a prosthesis.

The antireflux prosthesis has had excellent results and simplified surgical treatment of this condition. At about 20 minutes, actual operative time is considerably reduced compared with traditional hiatal hernia repairs. From 1973 to 1982, 174 patients underwent surgery with a specified follow-up series of UGI radiological studies. There were no mortalities related to the prosthesis. Three patients had the prosthesis removed. Complications related to the prosthesis included its displacement in one patient in whom the knot slipped. The prosthesis was replaced with excellent results. In one instance, a spleen laceration necessitated a splenectomy. Fifty patients experienced transient dysphagia for two to six weeks or longer but with no problems after the dysphagia subsided. Twenty-three were determined through x-ray to have had the prosthesis migrate above the diaphragm due to a large hiatus. In all of these 23 patients, the prosthesis remained at the gastroesophageal junction, and they remained asymptomatic. Perioperative nursing care and teaching closely follows that of traditional hiatal hernia repair with a shorter and less traumatic recovery.

Gastroesophageal Reflux↗

Factors influencing theophylline serum protein binding.

We studied a number of influences on theophylline binding to serum proteins using equilibrium dialysis (37 degrees), a modified Krebs-Ringer bicarbonate buffer (pH 7.4), and 8-14C-theophylline with unlabeled theophylline (30 microgram/ml) added to sera from healthy subjects. Theophylline protein binding rose by 18.6% as pH rose from 7.0 to 7.8 (percent theophylline bound = 28.2 +/- 4.3 at pH 7.0 and 46.8 +/- 4.9 at pH 7.8, n = 5). Average theophylline binding to the proteins at 37 degrees in serum samples from 10 normal adults was 39.3 +/- 3.44%, which is 89.9% lower than the average of 48.2 +/- 3.74% for the same samples at 26 degrees. Theophylline binding was 6.1% higher with 0.1 mole/l phosphate buffer, pH 7.4, than with a modified Krebs-Ringer bicarbonate buffer, pH 7.4. Of the 19 drugs and metabolites tested for competition with theophylline for binding sites on serum proteins, 10 induced decreases in binding ranging from 6.8% in the case of furosemide to 18.3% for sodium salicylate. The latter was the only drug that induced a decrease in theophylline binding at concentrations that would be achieved in the therapy of same patients (i.e., patients on long-term salicylate therapy). All the other drugs that decreased theophylline binding did so at much greater concentrations than their usual therapeutic levels. The mean +/- SD of theophylline bound in 51 fresh serum samples from healthy adults was 48.6 +/- 10.2%; the pH of these specimens varied from 7.6 to 8.7. After adjusting pH to 7.4, theophylline binding was lowered to 37.6 +/- 4.5% and intersubject variability decreased. We recommend that the pH of serum specimens be adjusted to 7.4, or to the original pH of the blood specimen if it differs significantly from 7.4 (i.e., in acidotic or alkalotic patients). The wide range of reported values for theophylline binding to serum proteins in normal and asthmatic adults at least partly results from differences in the conditions used for the separation of free from bound drug.

Blood Proteins↗

Application of response surface methodology to the assay of gamma-glutamyltransferase.

Response surface methodology (RSM) offers an empirical approach to the study of clinical enzyme assays. Variables such as pH, which are difficult to characterize by using theoretical enzyme kinetics, are easily included in RSM formulations. In this investigation, we studied with RSM the change in the measured activity of gamma-glutamy-transferase (EC 2.3.2.2) as a function of changes in concentrations of donor (gamma-glutamyl-3-carboxy-4-nitroanilide) acceptor (glycylglycine), and pH. The study defined large ranges for these variables over which maximum enzyme activity is obtained: donor 6.6 to 10.2 mmol/L, acceptor 129 to 250 mmol/L, and pH 7.8 to 8.5. The RSM regression polynomial was as accurate as a previously determined enzyme kinetic equation for predicting the transferase activity from given reagent substrate concentrations. Although not yielding a mechanistic understanding of an enzyme assay, RSM studies do produce an operational understanding of how an assay functions.

Clinical Enzyme Tests↗