PubMed HealthSearch

Biomedical subjects

D G Watts

Publications and source records attributed to D G Watts.

10 recordsLinked to original sources

Determining confidence intervals for parameters derived from analysis of equilibrium analytical ultracentrifugation data.

In the above discussion, we have introduced the profiling approach of Bates and Watts. It is an easy to implement, empirical approach to the determination of confidence intervals for parameters in nonlinear models. We have applied the approach to the analysis of equilibrium sedimentation data and have demonstrated that, although models for analyzing such data are formally nonlinear they are functionally linear. As such, linear approximation confidence intervals for the parameters are adequate for these models and data sets. Further, we have been able to examine the effect of implementing a multiple independent variable approach (in this case, using multiple rotor speeds) on the precision of the analysis. We found that the standard errors of the parameters were reduced and that this is accounted for by either the increase in the number of data points or the decreases in parameter correlation. In this case, profiling helped to visualize the effect on the sum of squares surface of reducing parameter correlation, making the effect of the small decreases in the correlation of some parameters more evident. Using profiling, it should be easy to explore other methods for the improvement of the analysis of ultracentrifugation data and to be able to quantitate the improvement. With the above discussion as an example, it is likely that the profiling approach should be quite useful and broadly applicable in the analysis of data in terms of nonlinear models.

Computer Simulation

Reproducibility of the pharmacokinetic-hemodynamic response to nitroglycerin in the dog: a model for studying the effects of chronic treatment.

We studied six dogs to determine the hemodynamic response to and pharmacokinetics of intravenous nitroglycerin (i.v. GTN) before and after a five-day treatment with placebo ointment. On the first study day, the major hemodynamic response to 21 micrograms/min i.v. GTN was an 11.4% +/- 5.6 (S.D.) fall in systolic blood pressure (SBP) from a control of 180 mmHg +/- 16 to 158 mmHg at 21 micrograms/min i.v. GTN. This finding was reproduced (a 12.6% +/- 5.6 fall in SBP) on the second study day. On the first day, the relationship between the arterial GTN concentration and the infusion rate was linear, the arterial t1/2 for GTN was short (1.9 min +/- 0.6) and there was an 80% arterial-venous extraction for GTN; these values were unchanged by five days of treatment with placebo. We conclude that this model is a sensitive and reproducible system for studying the in vivo effects of sustained drug treatment.

Animals

Biases in the measurement of arterial pressure.

We compared cuff to simultaneous direct intra-arterial pressure in 26 seriously ill patients, in order to: test the accuracy of oscillometric and auscultatory estimates of direct systolic pressure; test muffling and disappearance of sound as indices of direct diastolic pressure; gain insight into the timing of the different phases of Korotkoff sounds; and assess the local and general effects of cuff inflation on blood pressure. We found that conventional estimation of systolic blood pressure by auscultation of the first Korotkoff sound (K1) underestimates direct systolic pressure by an average of 16 to 17 mm Hg. Oscillometric pressure measurement provides a significantly better estimate than K1 but still underestimates by 7 to 8 mm Hg. These systolic cuff measurements are biased downward from direct values because of local cuff effect and cuff error. Diastolic cuff measurements deviate from direct values primarily because of a local cuff effect which produces an upward bias of 5 mm Hg at the point of sound muffling (K4), and 3 mm Hg at the point where sounds disappear (K5). We recommend oscillometric measurement of systolic pressure and K5 measurement of diastolic pressure as the best indirect estimates of blood pressure in critically ill patients.

Aged

Steady state pharmacokinetic haemodynamic studies of intravenous nitroglycerin in congestive cardiac failure.

We conducted pharmacokinetic haemodynamic studies in 10 patients with congestive cardiac failure to determine both the time to steady state concentration after commencement of a standard infusion rate of 21 micrograms/min i.v. GTN and the haemodynamic response once steady state plasma concentration ws achieved. Nitroglycerin was detected in plasma 2 min after commencement of the infusion, the concentration rose to a peak of approximately 4 ng/ml at 30 min and was maintained throughout the balance of the infusion period. During GTN infusion heart rate, systolic blood pressure and cardiac index were unchanged; there was significant declines (P less than 0.01) in pulmonary systolic pressure (SPA) (52 to 42 mm Hg), pulmonary capillary wedge pressure (PCWP) (26 to 20 mm Hg), and right atrial pressure (RAP) (12 to 8 mm Hg). These pressure changes were first evident within 5 min, approached maximum by 10 min and were maintained throughout the remainder of the infusion period. A one compartment model fitted to haemodynamic and GTN data revealed time constants (+/- approximate standard error) for SPA, PCWP, RAP and GTN of 8.2 (3.4), 9.7 (3.0), 8.1 (3.8) and 8.1 (1.9 respectively. Clearance for GTN was 6.2 +/- 2.7 (s.d.) 1 min. These data demonstrate steady state concentration of GTN is approached asymptotically with a time constant of 8.1 min during i.v. infusion of 21 micrograms/min. The time constants for haemodynamic measurement most sensitive to GTN's effect, i.e. SPA, PCW and RAP were remarkably similar to the time constant found for GTN concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Clinical trials:randomization before consent.

Conventional blind randomized trials involve obtaining consent for treatment prior to randomization into control or treatment groups. When the trial is of necessity an open one, obtaining consent to treatment and then assigning the patient to a control group may lead to undesirable consequences. When consent is required prior to randomization, inability to obtain it diminishes both control and treatment numbers. Obtaining consent after randomization enhances the power of the study since refusal affects only treatment numbers thus making more efficient use of patient material. We propose to analyze the outcome of patients allocated to treatment, but refusing experimental therapy, as a separate group. Comparison of this group with the control population will permit validation of the efficacy of the randomization process and allow testing of the hypothesis that refusers of consent react the same as the control population. If no difference occurs we propose that the refuser and control groups be combined and compared with those patients who receive experimental treatment.

Clinical Trials as Topic

Microwave radiometry and its potential applications in biology and medicine: experimental studies.

This paper presents experimental data on : (1) the natural emission of microwave radiation by biological systems, and (2) the effect of drugs as well as microwave radiation on specimen microwave emission. Experiments were conducted on guinea pigs, mice, rabbits, and human subjects. The results were obtained with two different radiometers, one of the correlation type and one of the Dicke type, operating in the X-band at about 9 GHz with a sensitivity of approximately 0.1 degrees K. The results demonstrate the feasibility of this technique and suggestions are made for its use in bilogy, medicine, and in the field of biocommunications.

Allylisopropylacetamide