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Biomedical subjects

J F Gross

Publications and source records attributed to J F Gross.

At least 37 records · Page 2Linked to original sources
PubMed1982

Vasomotion, tissue fluid flow and the formation of lymph.

Spontaneous vasomotor activity was studied in the sandwich window preparations of the subcutaneous fasciae of the dorsal skin of rats. Measurements of the periodic changes in diameter related to the length of the active vessel show that this phenomenon causes substantial periodic volumetric displacements in tissue. We propose the hypothesis that these volumetric displacements are partially made up by tissue displacement, and are partially due to displacement of the tissue fluid. The tissue fluid motion due to anteriolar vasomotion compared with the net tissue fluid motion due to fluid exchange from the corresponding number of capillaries, shows that these two effects are similar in magnitude. We propose the hypothesis that this periodic motion of fluid in the tissue constitutes an additional mechanism by which tissue fluid is propelled into the terminal lymphatics.

Animals↗
PubMed1981

[The role of mathematical models in microhemorheology (author's transl)].

The basic fluid-mechanical and structural elements that determine the microhemorheological behavior of blood are presented and discussed. Microhemorheological models are classified into three groups: empirical models, theoretical models, and hybrid models. Major contributions in each area are reviewed and the state-of-the-art in microhemorheological modelling is discussed. Finally, important areas of future research are delineated.

Biomechanical Phenomena↗
PubMed1980

Concentration profile for the dissolution of drug tablets undergoing simultaneous degradation.

An empirical approach to the concentration-time history of a dissolving drug has resulted in a cube-root equation in which the characteristic constant of the equation embodies the important physical variables of the system. This expression has been used to study the dissolution of a drug that degrades simultaneously in the test solution. An alternative representation of the dissolution process is first-order kinetics. These two approaches are compared by fitting the experimental data of the dissolution of digoxin and melphalan tablets in various media, and a new method for the proper analysis of data for the dissolution of tablets that simultaneously degrade in the test solution is presented.

Chemistry, Pharmaceutical↗
PubMed1980

Intra-arterial infusion of anticancer drugs: theoretic aspects of drug delivery and review of responses.

A linear, physiologically based pharmacokinetic model has been used to study drug delivery characteristics of anticancer drugs after both iv and intra-arterial infusion. It confirms the general belief that intra-arterial infusion produces an increase in local tissue levels and a reduction in systemic drug availability. The increase in local drug concentration depends largely on the blood flow rate of the infusing artery and the rate of drug elimination by the rest of the body. A low arterial blood flow rate and a high drug elimination rate will ensure a high local drug level. On the other hand, the reduction of systemic drug delivery depends on the ability of the infused region to eliminate the drug. Lower systemic availability will be obtained if a substantial amount of the drug is removed during the first pass through the infused region. A review of the clinical response rates of five cytotoxic drugs (Adriamycin, bleomycin, 5-fluorouracil, melphalan, and methotrexate) infused intra-arterially as single agents indicates that, despite a general belief in the advantages of intra-arterial infusion, only 5-fluorouracil shows a significant increase in response rate in the treatment of cancer when compared to systemic routes of administration. There appears to be no justification for the higher costs and substantial risks of intra-arterial infusion for the other drugs due to the lack of controlled studies and the lack of a substantial increase in the response rates. It is suggested that a future controlled study be required to validate the claims of superiority of intra-arterial infusion therapy.

Antineoplastic Agents↗
PubMed1980

Microcirculatory studies in rat mammary carcinoma. I. Transparent chamber method, development of microvasculature, and pressures in tumor vessels.

Fragments of a mammary adenocarcinoma were implanted into transparent tissue chambers in the dorsal skin flaps of female inbred F344 rats. A chamber modification permitted repeated access to the tissue without infection, vessel disruption, or impairment of tumor growth. Tumors completely filled the chambers after 26-30 days. Development of tumor microvasculature was characterized by increase in number, length, and diameter of vessels. These changes were much more pronounced in capillaries and venules than in arterioles. Direct blood pressure measurements were performed in microvessels throughout the tumor during the first 3 weeks of growth as well as in microvessels of tumor-free control preparations containing subcutaneous tissue. Average pressures in arterioles of 40- to 11-micron diameter were between 23.0 and 17.3 cm H2O in tumors versus 25.5 and 16.2 cm H2O in controls. Average pressures in venous capillaries, venules, and veins up to 150-micron diameter were between 9.1 and 8.1 cm H2O in tumors and between 13.4 and 11.0 cm H2O in controls.

Adenocarcinoma↗
PubMed1979

Kinetics of intravenous melphalan.

We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High-pressure liquid chromatography and 14C-melphalan were used to assay drug concentration in plasma and urine. Composite plasma t1/2alpha was 7.7 +/- 3.3 and t1/2beta was 108 +/- 20.8 min for 8 of the patients. The mean 24-hr urinary excretion of melphalan was 13.0 +/- 5.4% of the administered dose. In 2 patients, 80% to 100% of the measured 14C counts in plasma and urine samples at each study interval, up to 24 hr after drug administration, could be accounted for by the sum of parent compound, monohydroxy and dihydroxy products, and methanol nonextractable radioactivity (i.e., protein-bound activity). These data and evidence of rapid disappearance from plasma at 37 degrees in vitro suggest that spontaneous degradation, and not enzymatic metabolism, is the major determinant of the t1/2 of melphalan in vivo.

Adult↗
PubMed1979

Pharmacokinetics of drugs subject to enterohepatic circulation.

The influence of the changes in biliary excretion and reabsorption rates on the pharmacokinetics of drugs subject to enterohepatic circulation was examined analytically. A recently proposed two-compartment model with drug elimination occurring in each compartment was adapted to represent the body and the GI tract. Enhanced reabsorption was equivalent to biliary excretion rate reduction, except that the latter always decreased alpha and prolonged the alpha-phase half-life while the former always increased alpha and shortened the half-life. However, depending on the relative values of the two elimination rate constants, biliary excretion reduction (or reabsorption enhancement) could either increase or decrease the terminal drug half-life (beta-phase). Whether the terminal drug half-life was prolonged or shortened, a biliary excretion reduction always increased the area under the plasma decay curve for intravenous and oral doses and also raised the steady-state drug level in the body for constant-rate intravenous infusion. As a consequence, the lethality, toxicity, or effectiveness of the drug will be increased for patients with impaired bile flow or enhanced drug reabsorption; therefore, the clinical dosage may have to be reduced.

Enterohepatic Circulation↗
PubMed1979

Clearance constants in physiologically based pharmacokinetic models.

The intrinsic clearance of an organ is usually approximated by the apparent clearance from that organ in the development of a physiologically based pharmacokinetic model. In this study, the exact relationship between the two clearances was derived and analyzed. When the extraction ratio of the drug was small (less than 0.05), the approximation was reasonable. However, when the extraction ratio was high (greater than 0.2), serious errors could be made by using the approximation. These errors could be as much as 50% reduction in the estimated extraction ratio and as much as an order-of-magnitude difference in the intrinsic clearance.

Kinetics↗
PubMed1979

Physiologically based pharmacokinetic models for anticancer drugs.

The rationale and history of the development of physiologically based pharmacokinetic models are briefly reviewed in this paper. The methods of model construction and the previous application of this type of model to anticancer drugs are discussed. Future research should be focused on the following areas: (1) interspecies scaling, (2) the effects of disease states on the pharmacokinetics of anticancer drugs, and (3) the applications of pharmocokinetics to the studies of growth behavior of cancer cells. The ultimate goal will be to utilize this basic information to design an optimal dosage regimen and treatment schedule for the safe and effective cancer chemotherapy of each individual patient.

Ancitabine↗
PubMed1979

Estimation of tissue-to-plasma partition coefficients used in physiological pharmacokinetic models.

An important parameter in the development of pharmacokinetic models is the ratio of tissue drug concentration to the concentration of the drug in the arterial plasma or the effluent plasma. The relationship between these two tissue/plasma ratios is derived analytically for different routes of drug administration. The two are equal only in compartments with no elimination when the drug is infused at constant rate. For other routes of administration, the two ratios are identical in all compartments only when there is no elimination process. The tissue/plasma concentration ratios for infusion equilibrium are not equal to the corresponding values for the postdistribution phase after an intravenous bolus injection. When the plasma concentration for infusion and injection are the same, more drug will appear in the lung during infusion steady state than during the postdistribution equilibrium. The reverse is true for the other organs. The importance of properly defining the tissue/plasma ratio and its implication for pharmacokinetic modeling are discussed. The results may have important therapeutic implications for the availability of drugs using different routes of administration.

Absorption↗
PubMed1979

Analysis of oxygen diffusion from arteriolar networks.

A mathematical model of oxygen transport in the precapillary microcirculation is presented. The theory is then used to simulate oxygen distribution in the arteriolar network of the hamster cheek pouch. Theoretical prediction of transmural and longitudinal oxygen tension (PO2) gradients is in qualitative agreement with available experimental data. The effect of the variation of inlet network PO2, blood flow rate, blood hematocrit, and other parameters on the transport characteristics is studied. The calculations predict that the luminal PO2 in small arterioles is practically independent of the inlet network PO2 leve if the latter is sufficiently high; when this inlet PO2 level is low, then the longitudinal gradients of luminal PO2 vanish. It is further shown that retardation of blood flow may cause a significant increase in precapillary oxygen losses.

Animals↗