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Biomedical subjects

J Aroesty

Publications and source records attributed to J Aroesty.

18 recordsLinked to original sources

The diffusion of magnetic resonance imaging scanners in a changing U.S. health care environment.

Technological aspects and early clinical experiences are arousing great enthusiasm over magnetic resonance imaging (MRI). However, influences such as regulation, reimbursement, and increasing competition also are playing important roles in determining the diffusion of this new technology. Of these considerations, competition among providers seems the most important. Competition related to MRI is manifested as direct competition over MRI services, using MRI to improve a provider's strategic position and competition among specialties. In making decisions concerning MRI acquisition and operation, providers are drawing upon their experiences with computed tomography (CT) to help them determine when would be the best time for acquisition, how to decide whether acquisition is appropriate, and how best to acquire, operate, and market the technology.

Communication↗

Hemodynamic determinants of thallium-201 lung uptake in patients during atrial pacing stress.

The present investigation was undertaken to define the hemodynamic determinants of lung uptake of thallium-201 (TI-201) in man during stress. Graded tachycardia was induced by atrial pacing with continuous hemodynamic monitoring in 21 patients (6 normal, 15 with coronary artery disease). At peak pacing, 80 MEq (2.2 mCi) of TI-201 was injected intravenously and imaging commenced within 5 minutes. Lung activity was expressed as a percentage of peak myocardial activity on the anterior image (Lung TI-201 Index). The influence of rest, peak and post pacing hemodynamic parameters including cardiac index, pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, pulmonary artery pressure, and heart rate on Lung TI-201 Index was examined using step-wise multiple regression. Change in cardiac index from rest to peak pacing was negatively correlated, while pulmonary capillary wedge pressure at peak pacing was positively correlated to Lung TI-201 Index (combined r value of 0.75). No other parameter had a significant correlation. In summary, lung uptake of TI-201 activity during atrial pacing stress appears to depend on: changes in cardiac output which may determine tissue contact time and thus influence extraction efficiency, and hydrostatic pressure in the pulmonary capillary bed.

Adult↗

Adoption and diffusion of a new imaging technology: a magnetic resonance imaging prospective.

Adoption of magnetic resonance imaging (MRI) by individual purchasers and by the health care system will be influenced by many factors. A framework for considering these influences is offered, incorporating them into four major considerations: (1) MRI and its attributes--the technology, its safety and efficacy, and the benefits of acquisition; (2) communication channels--commercial and professional; (3) time for consideration of adoption and experiential testing; and (4) the medical system--including potential acquirers, health planning, and reimbursement. Among these, positive, negative, and variable influences affecting adoption can be identified. Factors that should most strongly motivate early adoption are the potential of the technology for providing new and useful clinical information and the competitive and economic benefits that early acquirers might enjoy. Important discouragements include the possibility of early obsolescence and that MRI represents an economic risk under diagnostic-related-group reimbursement. The less risky approach for most practices is to delay acquisition of MRI pending further experience with the technology and the changing reimbursement climate. Institutions that are primarily interested in the research potential of MRI or that are large enough to sustain the economic risks should consider earlier acquisition.

Health Planning↗

A preliminary model of double-minute-mediated gene amplification.

A mathematical model of double minute (dm) population dynamics has been developed based upon current concepts of the saltatory replication, random partitioning, nuclear exclusion and loss, and cellular growth inhibition of these extrachromosomal elements. A highly accurate approximate analytical solution has been obtained for the dm frequency distribution at steady state and preliminary analysis of transient states has been performed. The steady state solution has been fit to experimental frequency data of the SW527N carcinoma line, the excellent goodness of fit (X2 = 2.6, d.f. = 29) providing preliminary evidence for the consistency of this set of mechanisms. Two special cases are examined in which extrareplicative dms are produced on both the chromosome and existing dms at equal rates or on the chromosome alone. The model predicts that the population--average rate of extrareplicative dm production is 0.039 +/- S.E. 0.009 dms/hr/cell in the first case and is tenfold higher than when such replication occurs on the chromosome alone (0.0043 +/- S.E. 0.0004 dms/hr/cell). Allowable ranges of the extent of dm-related growth inhibition and dm loss are determined for the SW527N cell line. It is found that dm-related growth inhibition can be nearly as high as that observed for the S180 sarcoma lines (on the order of 0.5% per dm lengthening of the doubling time) or as low as zero.

Animals↗

Pharmacokinetics of high-dose methotrexate with citrovorum factor rescue.

The methotrexate (MTX)-plasma concentrations of 172 high-dose infusions over the range of 50-200 mg/kg were measured over the 72-hour period following the beginning of infusion. Pharmacokinetic analysis shows that a biexponential function adequately describes the plasma decay for all doses. The distribution of plasma clearances over the patient population at a given dose has been characterized by a biexponential clearance function and associated time-dependent variance. It is found that when each of the plasma clearance functions are scaled by their respective dose, the 1 SD bands about the resulting unit dose curves overlap throughout their time ranges and are therefore insignificantly different from one another. Thus, the plasma clearance over the 50-200-mg/kg range may be represented by a single dose-scalable biexponential model with half-lives of 1.8 +/- 0.1 and 8.4 +/- 0.5 hours. For a given maximum allowable plasma-MTX level (eg, 10(-5) M at 24 hours), the variance of the clearance distribution is shown to predict the expected fraction of patients who will require intensified rescue. Urinary clearance has been determined at 104 +/- 8 ml/minute over the dose range of 50-300 mg/kg and only 60% of the MTX was excreted in the urine by 72 hours.

Adolescent↗

Computer simulation of leukemia therapy: combined pharmacokinetics, intracellular enzyme kinetics, and cell kinetics of the treatment of L1210 leukemia by cytosine arabinoside.

An integrated mathematic computer-based model of the pharmacokinetics, intracellular enzyme kinetics, and cell kinetics of the treatment of L1210 leukemia by cytosine arabinoside (ara-C) is described. The compartment model of Bischoff and Dedrick is extended to the intracellular level by inclusion of equations describing the phosphorylation, dephosphorylation, and deamination of ara-C with enzymatic feedback control. The activities of kinase, deaminase, and phosphatase are explicitly included in the models and are estimated from relevant data. Cell proliferation is described by a continuous-flow mathematic model in which cellular maturation and cell-to-cell variability in maturation rates are key variables. Cell proliferation is related to intracellular biochemistry through mathematic expressions which relate cell lethality and progression delay to the time course of intracellular ara-CTP. In vitro and in vivo experiments performed in a number of laboratories are compared by simulation. The most sensitive parameters in dose-response and cell-survival simulations are deoxycytidine kinase activity, ara-CTP half-life, renal clearance of ara-C, and cell-kinetic parameters for proliferation and cell killing. Progression delay is vital to the realistic simulation of divided-dose schedules. By comparative simulation we have identified areas of uncertainty which can be classified by a few additional measurements. The applications of simulations combining pharmacokinetic, biochemical, and cell-kinetic data in vitro and in vivo are discussed, exploring consistency among different measurements, and relating experimental protocols to clinical treatment.

Animals↗

Disposition of cytosine arabinoside (NSC-63878) and its metabolites: a pharmacokinetic simulation.

A computer-based model of the pharmacokinetics of cytosine arabinoside (ara-C) and its active metabolite, ara-CTP, has been developed. This model, which is an intracellular extension of the Bischoff-Dedrick model of multi-organ pharmcokinetics gives predictions which are in agreement with the recent measurements of Chou et al on tissue concentrations of ara-CTP and Borsa et al on blood levels of ara-C. It is shown that the ara-CTP halving time in tissue is much greater than the ara-C halving time in blood because of low tissue levels of phosphatase. For a single dose at the LD10 level in mice, significant splenic DNA inhibition is calculated to occur for 26 hours, while the ara-C levels are negligible in 6 hours. The calculated duration of cytostatic effect at lower dosages (2.5 mg/kg) is 10 or 12 hours, while ara-C blood levels are negligible within 3 hours. Implications for cell kinetics and scheduling studies are also briefly described.

Animals↗