Biomedical subjects
Publications and source records attributed to R A Hamilton.
The Michigan Health Data Corporation is a major reason why Michigan enjoys voluntary handling of health care data, it is also a potential cornerstone for continuance of a voluntary, but controlled, vehicle for exchanging necessary information.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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This study was conducted to determine the reliability of two methods of predicting maintenance warfarin dosage. Fifty-nine patients were studied using Method 1 and 44 using Method 2. Both methods produced a statistically significant correlation between predicted and actual dose for the two populations. However, actual vs. predicted doses for individual patients were significantly different. Method 1 predicted a dose within +/- 2.5 mg/d of actual dose in only 40.7 percent of patients. With Method 2, the corresponding value was 56.8 percent. Although the linear regression was statistically significant in our population, many patients would have excessive or subtherapeutic dosage predictions.
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Lidocaine pharmacokinetics were studied in five fibrillated dogs undergoing external cardiopulmonary resuscitation (CPR) and five comparable control dogs. All animals were anesthetized with sodium pentobarbital and their electrocardiogram, arterial blood pressure, left ventricular pressure and carotid blood flow were monitored continuously. All dogs received a 2 mg/kg i.v. bolus dose of lidocaine. Multiple blood samples from venous, arterial, left ventricular and right atrial sites were obtained for determination of blood lidocaine concentration. At 60 min, the dogs were sacrificed. Lung, liver, kidney, brain, skeletal muscle and heart tissue samples were collected. There were dramatic differences between the control and CPR groups in arterial pressure, left ventricular pressure and carotid blood flow. In the CPR dogs, lidocaine blood concentrations for the entire 60 min were significantly higher than the control dogs and lidocaine clearance was reduced at least by 8-fold. A comparison of extraction ratios across skeletal muscle demonstrated that the phase of tissue uptake was prolonged in the CPR group. In each of the tissue samples, significantly higher tissue concentrations were observed in the CPR group. The results of our study show that lidocaine disposition is greatly altered during CPR and this is most likely due to a tremendous reduction of cardiac output and blood flow during CPR.
Determinations of single serum drug concentrations are useful in monitoring drug therapy. A mean serum level would supply more information but is expensive and laborious because of the multiple blood samples and assays, calculation of area under the curve (AUC) by the trapezoidal rule, and division of the AUC by the time interval during which the samples were drawn. A method was devised that pools aliquots from individual serum samples taken during the testing period to form on composite sample. A single assay of this sample provides the mean serum level of the testing period. The method was successfully tested with amaranth and then applied to valproic acid serum levels. AUC and mean serum levels were determined by the standard procedure of assays of multiple samples and the trapezoidal rule. Mean serum level was also determined by the pooled sample technique. The correlation coefficient for the comparison of the mean serum levels determined by the two techniques is 0.907 (p less than 0.001). There was no difference between the estimates of the mean serum levels by Student's paired t test (t = 0.693, p greater than 0.2). The good correlation and lack of difference between the conventional method and the pooled sample method indicates that the method is valid.
The effect of food on valproic acid absorption was investigated in a randomized, cross-over study with eight subjects. Two 250-mg soft-gelatin capsules of valproic acid were administered to the participants under fasting and nonfasting conditions. The time of peak serum concentration, height of the peak concentration, and total area under the curve were determined and compared by the Student's t test for paired data. The time to attain a peak serum concentration was significantly delayed (p less than 0.005) from the 1.6 hours during fasting conditions to four hours after a standard meal. A statistically insignificant trend toward lower peak serum concentrations (54.6 micrograms/ml versus 49.4 micrograms/ml) was found under the nonfasting conditions. This trend becomes significant if the data of one subject who exercised before taking the drug are eliminated. The area under the curve was not different between the two conditions. The administration of the drug with food did not significantly alter the volume of distribution, half-life, or elimination constant. No clinically important interaction resulted from the administration of valproic acid with food. If a patient experiences gastrointestinal side effects with valproic acid, the patient may be advised to take the drug with food.
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A matched-pair case-control analysis of Medicaid claims was performed to determine the risks of hospitalization associated with drug-drug interactions. Patients were hospitalized and controls were not. They were randomly matched based on contemporaneous eligibility for Medicaid benefits. Odds ratios for hospitalization in patients exposed to known drug-drug interactions were compared with those in patients exposed to one of the interacting agents. When confidence intervals did not overlap, the odds ratio was considered to be significantly increased. Odds ratios were significantly increased for many interacting drug pairs, and were associated with commonly recognized interactions as well as less widely recognized ones. Cimetidine interactions achieved significance only with theophylline. In the Medicaid population, exposure to a number of drug-drug interactions was associated with a significantly increased risk of hospitalization.