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M E Burton

Publications and source records attributed to M E Burton.

11 recordsLinked to original sources
PubMed1992

Decreases in albumin/creatinine and N-acetylglucosaminidase/creatinine ratios in urine samples stored at -20 degrees C.

The effects of storage for 6 months or 2 years at -20 degrees C were studied in urine samples from Type II diabetic patients by assaying albumin by immunoturbidity, N-acetylglucosaminidase (EC 3.2.1.30) by methoxynitrovinylphenol release, and creatinine by the Jaffé method. There were significant decreases (P < 0.001) in albumin/creatinine ratios from 1.14 (0.63-2.98) to 0.83 (0.32-2.12) g/mol (median + interquartile ranges) after 6 months (n = 97), and from 1.64 (0.74-5.72) to 1.00 (0.37-4.54) g/mol after 2 years (n = 89). The percentage of samples with results below the detection limit of the albumin assay (2 mg/L) increased from 5% to 21% after 6 months and from 0% to 34% after 2 years. N-Acetylglucosaminidase/creatinine ratios decreased (P < 0.001) from 520 (358-832) to 380 (263-695) U/mol after 6 months and from 520 (330-865) to 258 (82-462) U/mol after 2 years. The effect of storage was greater in samples with concentrations in the normal range (< 2.5 g/mol for albumin/creatinine, < 500 U/mol for N-acetylglucosaminidase/creatinine). Samples with albumin concentrations more than twice the normal range were still detected as abnormal after storage at -20 degrees C; e.g., 18% were > 5 g/mol (albumin/creatinine) initially, with 17% > 5 g/mol after 6 months of storage. We therefore recommend storage of urine samples at 4 degrees C for no longer than 7 days before assay.

Acetylglucosaminidase↗
PubMed1991

A controlled trial of the cost benefit of computerized bayesian aminoglycoside administration.

We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections. Patients were randomized to a control (dosing based on physician choice; n = 75) or experimental group (dosing based on the bayesian program; n = 72). Both groups used serum aminoglycoside concentration data when making dosing decisions. Improved response rates were seen in the experimental (60%; 42/68) compared with the control group (48%; 36/68). A higher, but not statistically significant, incidence of toxicity was found in the control (7/75; 9.7%) versus the experimental group (4/72; 5.1%). Mean length of total hospital stay was significantly longer for patients in the control group (20.3 days) compared with the experimental group (16.0 days) (p = 0.028). The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy. On the basis of a reduced length of stay, a potential cost savings of $1311 per patient can be achieved.

Aminoglycosides↗
PubMed1989

Evaluation of a Bayesian method for predicting vancomycin dosing.

The purpose of this study is to evaluate the performance of a vancomycin dosing program in predicting dosages necessary to achieve desired serum vancomycin concentrations in a relatively large patient population. With the completion of initial performance evaluation, revised pharmacokinetic parameter estimates derived in the initial evaluation are used to reevaluate program performance. The program uses population estimates of vancomycin's volume of distribution (Vd) and clearance (Cl) to initially predict dosing, then individualizes those estimates by a Bayesian algorithm (iterations) which uses dosing and the resulting serum vancomycin concentration data. Use of the Bayesian forecaster with one iteration significantly increases the calculated Cl value as compared with population estimates; two and three iterations significantly increase both Vd and Cl when compared with population estimates. Absolute values of the predicted minus observed peak serum vancomycin concentrations (accuracy) are 17.7 +/- 14.0, 6.1 +/- 3.6, and 3.4 +/- 2.1 mg/L for dosing using population estimates, Bayesian with one iteration, and Bayesian with two iterations, respectively. Similarly, accuracy of predictions for trough concentrations is 13.8 +/- 12.4, 3.5 +/- 3.2, and 3.2 +/- 2.6 mg/L for each method, respectively. Bias of dosing predictions in achieving desired peak and trough serum vancomycin concentrations is also significantly reduced by using the Bayesian algorithm. Use of the mean Vd and Cl values from three iterations as the starting parameters in a new group of 12 patients significantly improves program performance when compared with use of initial population parameters. Time of sampling for peak serum concentrations has no effect on program performance. In patients with impaired renal function, use of population estimates resulted in less accurate dosing prediction, but this less accurate performance was not observed with use of the Bayesian forecaster. These data demonstrate the accuracy and lack of bias in individualized dosing predictions using the Bayesian dosing method and the ability of revised pharmacokinetic parameter estimates to improve performance.

Bacterial Infections↗
PubMed1989

Issues in methodology and applications for therapeutic monitoring of antidepressant drugs.

Measurement of antidepressant drugs in serum provides a useful indicator of optimal dosage and can enable the clinician, in certain circumstances, to easily adjust dosages for individual differences in drug metabolism, alterations in the concentration in serum owing to drug interactions, or failure to achieve an adequate concentration in serum because of noncompliance. Practical therapeutic monitoring of antidepressants, however, is still complicated by a lack of suitable reference methodology or established assay-performance criteria and the diversity of analytical techniques. We review here several contemporary methods of analysis for the tricyclic antidepressant drugs--including gas chromatography with a nitrogen-specific detector, HPLC, and immunoassays--that are available for toxicology screening or for quantifying the most widely monitored tricyclic drugs. We also present an overview of current laboratory issues and practical considerations facing those who analyze for antidepressant drugs.

Antidepressive Agents, Tricyclic↗
PubMed1989

Determination of serum desipramine and 2-hydroxydesipramine for pharmacokinetic applications by HPLC with ultraviolet detection.

This procedure for measuring desipramine and its 2-hydroxy metabolite in serum at a minimum concentration of 1 micrograms/L involves high-performance liquid chromatography (HPLC), with ultraviolet detection at 214 nm. After desipramine and 2-hydroxydesipramine are extracted from alkalinized serum by a single-step solvent extraction, they are separated by HPLC and quantified with amitriptyline as the internal standard. Desipramine, 2-hydroxydesipramine, and amitriptyline are separated in 6 min. The standard curve is linear (r = 1.000) for both desipramine and 2-hydroxydesipramine concentrations over the range of 1 to 100 micrograms/L, and the assay demonstrates an excellent precision profile, even at low concentrations. Between-run CVs for 20 and 60 micrograms/L controls (n = 20) were 3.9% and 3.6% for desipramine and 3.4% and 3.8% for 2-hydroxydesipramine, respectively. In a pharmacokinetic evaluation of patients with depression, we examined single-dose elimination curves before and after a four-week regimen of desipramine treatment. The results showed that the method's simplicity and high precision render it ideal for pharmacokinetic studies of desipramine.

Alkalies↗
PubMed1986

Accuracy of Bayesian and Sawchuk-Zaske dosing methods for gentamicin.

The derived pharmacokinetic variable estimates from a Bayesian aminoglycoside dosing program were compared with those from the Sawchuk-Zaske method to determine which variable estimates were the most accurate in fitting the test dose and in predicting subsequent peak and trough serum concentrations. Data on 17 patients with moderately impaired but stable renal function were analyzed. All patients received gentamicin sulfate for treatment of their infections. To determine the individualized variables using the Bayesian program, demographic data, dosing history, and one (midpoint), two (peak and trough), or four serum drug concentrations were entered into the program. The Sawchuk-Zaske method used three serum concentrations determined following a first dose or four concentrations before and after a subsequent dose to derive individualized pharmacokinetic variables. The estimates of pharmacokinetic variables determined using the Bayesian method with one, two, or four serum concentrations did not differ significantly from those obtained using all the available serum concentrations with the Sawchuk-Zaske method. Although the actual numeric differences of prediction, absolute, and squared errors for fitting the test dose were minimal, significant differences were seen. All methods were similar in predicting serum concentrations from continued dosing. For the prediction error from continued dosing, a slight but significant difference was observed with the Bayesian method using one serum concentration when compared with the other methods. The Bayesian method using one, two, or four serum gentamicin concentrations individualized pharmacokinetic variables as well as the Sawchuk-Zaske method.

Aged↗
PubMed1985

A Bayesian feedback method of aminoglycoside dosing.

We assessed the accuracy of a Bayesian method in providing dosing regimens to achieve desired serum aminoglycoside concentrations. This method calculates individual kinetics based on serum drug concentration data. Performance was analyzed by determining accuracy, bias, correlations of observed to desired serum drug concentrations, and the ability to achieve a target serum drug concentration. We also compared results from the Bayesian method with those resulting from the use of the predictive algorithm portion of the computer program and with routine physician dosing. The Bayesian method resulted in a high correlation coefficient (r = 0.913) between observed and predicted serum concentrations. Analysis of peak aminoglycoside concentrations indicated that the Bayesian method was more accurate and less biased than the predictive algorithm portion of the program or routine physician dosing. A similar trend occurred for trough concentrations. Finally, there were no statistically significant differences between the predicted and observed peak (6.4 +/- 1.5 and 5.9 +/- micrograms/ml) and trough (1.2 +/- 0.9 and 1.4 +/- 0.8 micrograms/ml) serum aminoglycoside concentrations with the Bayesian dosing method. There were significant differences for peak concentrations with the predictive algorithm portion of the program and for peak and trough concentrations with physician dosing. These data demonstrate the accuracy of the Bayesian dosing method in attaining desired peak and trough serum aminoglycoside concentrations.

Bayes Theorem↗
PubMed1975

Operative treatment of acromioclavicular dislocations.

An operation has been described for the treatment of Type Three acromioclavicular dislocations. It is in this type of case that previous operative procedures have proved to be unreliable, and in which conservative management has resulted in cosmetic deformity and progressive disability. The procedure of coracoacromial ligament transfer has been performed since 1952, and is adaptable for both fresh and chronic dislocations. The technic is simple and direct, and the material needed is both available and almost always uninvolved. The stability produced, after either repair without resection, or repair with resection of the clavicle, leads to a strong, stable shoulder. If there is any doubt as to the integrity of the joint, resection of the clavicle is to be preferred. The results to date have been encouraging, and in the opinion of this author, warrant further trial of this procedure.

Acromioclavicular Joint↗
PubMedDate not supplied

Comparison of drug dosing methods.

The literature reviewed herein clearly demonstrates the poor correlation between drug dosing and the ability to achieve a specific serum drug concentration and between drug dosing and clinical response, especially for drugs with a narrow therapeutic index. There is, however, a better correlation between serum drug concentration and observed clinical response. Thus, clinicians use serum drug concentrations to more accurately dose drugs. Numerous dosing methods have been developed in an attempt to improve the relationship between dosing, serum drug concentration, and response. The major hypothesis is that if dosing methods can be developed that will accurately predict serum drug concentrations, these methods would be useful in improving clinical care. Several dosing methods have been developed including use of 'standard' doses, population-based predictive algorithms and nomograms, pharmacokinetic equations, and Bayesian feedback. Some of these methods are accurate and useful, whereas others are not. This review evaluates the commonly used dosing methods (some of which utilise serum drug concentration feedback for dosage estimation) for 5 drugs: gentamicin, digoxin, phenytoin, theophylline, and lignocaine (lidocaine). These drugs were selected since they exhibit a representative cross section of pharmacokinetic parameters and since they exhibit a representative cross section of pharmacokinetic parameters and since they have narrow therapeutic ranges. An individualised method and a Bayesian method, both using serum drug concentration feedback, appear most accurate and precise in dosing to achieve desired serum drug concentrations and, hence, response. Our bias from personal experience with this method and from published use by others is that the Bayesian method is more flexible in that any number of serum drug concentrations may be used to determine dose, instead of the 3 or more required for the individualised method. Although use of these methods would appear to be cost-effective in timely provision of health care by reduction of toxicity and hospital stay, only sparse data have been generated to support this conclusion. Thus, further examination of the cost-effectiveness of drug dosing methods is necessary to establish their place in routine patient care.

Costs and Cost Analysis↗