Biomedical subjects

F J Vriesendorp

Publications and source records attributed to F J Vriesendorp.

23 records · Page 2Linked to original sources

PubMed1991

A method to quantitatively measure transcapillary transport of iodinated compounds in canine brain tumors with computed tomography.

We present a quantitative method for determining a blood-to-tissue influx constant (K1), a tissue-to-blood efflux constant (k2), and tissue plasma vascular space (Vp) that uses a computed tomographic (CT) scanner to make tissue and plasma measurements of the concentration of an iodinated compound. Meglumine iothalamate was infused intravenously over time periods of 0.5-5 min, up to 49 CT scans were obtained at one brain level, and arterial plasma was sampled over a 30- to 40-min period. K1, k2, and Vp were calculated for each voxel of the 320 x 320 matrix, using a two-compartment pharmacokinetic model and nonlinear least-squares regression. The method was used in dogs with avian sarcoma virus-induced brain tumors. As many as four studies on different days were done in the same animal. In tumor-free cortex, K1 of meglumine iothalamate was 2.4 +/- 1.7 microliter g-1 min-1 (mean +/- SD) and Vp was 3.4 +/- 0.5 ml 100 g-1. Mean whole-brain tumor K1 values ranged from 3.3 to 97.9 microliters g-1 min-1; k2 ranged from 0.032 to 0.27 min-1; and Vp ranged from 1.1 to 11.4 ml 100 g-1. These values were reproducible in serial experiments in single animals. Independent verification of K1 values was obtained with quantitative autoradiographic measurements of alpha-aminoisobutyric acid, which has similar physicochemical properties to meglumine iothalamate. The CT methodology is capable of demonstrating regional variation of transcapillary transport in brain tumors and may be of value in the study of human brain tumors.

Aminoisobutyric Acids↗

PubMed1987

The effect of systemic arterial hypertension on blood-to-tissue transport in experimental gliomas.

Systemic arterial hypertension was induced with epinephrine in 15 rats with 39 transplanted RG-2 brain tumors in an attempt to increase blood-to-tissue transport of a water-soluble compound. In 4 rats, hypertension was induced acutely (less than 5 sec), and in 11 hypertension was induced more slowly (over 5 min). Regional values of the unidirectional blood-to-tissue transfer constant (K) of alpha aminoisobutyric acid were measured with quantitative autoradiography. Mean arterial blood pressure (BP) over the experimental period increased from 117 +/- 17 mmHg (SD) to 168 +/- 18 mmHg in the rats with slowly induced hypertension, and from 124 +/- 4 to 142 +/- 5 mmHg in the acute hypertension group. Peak BP was 208 +/- 16 in the first group and 216 +/- 13 mmHg in the second. Intracerebral hemorrhage occurred in 10/15 animals, and there was disruption of BBB in tumor-free brain in 10/15 animals. Averaged mean whole tumor K of AIB in all hypertensive rats was 0.052 +/- 0.022 ml/g/min, compared to 0.037 +/- 0.015 ml/g/min in normotensive controls; there was no difference in mean tumor K between the two hypertensive groups. However, in intraparenchymal tumors without hemorrhage, K was only 0.039 +/- 0.013 ml/g/min. Although the mean K of AIB was higher in brain tumors of the hypertensive rats, the increase is unlikely to be meaningful in terms of augmented delivery of water-soluble drugs to brain tumors, and the high incidence of intracerebral hemorrhage countermands any clinical use of this approach.

Aminoisobutyric Acids↗

PubMed1987

Prediction of normal tissue damage induced by cancer chemotherapy.

Cancer chemotherapeutic agents have a low therapeutic index and require a precise and safe prescription. Hematological toxicity is the most common dose limiting side effect of cancer drugs. Therefore, Hemopoietic Stem Cells (HSC) are the most relevant targets for dose determination. Studies of total body irradiation with or without autologous bone marrow transplantation showed that HSC concentrations differ between mouse, rat, rhesus monkey, dog and man. A highly significant correlation was found between bone marrow rescue dose and kg body weight and not between bone marrow rescue dose and BSA. Kg body weight appears to offer a better prescription unit for cancer chemotherapy than BSA, because it correlates better with dose limiting, normal tissue, target cells. This prediction is borne out by the results of chemotherapy in neonates. BSA has also been used as dose unit for drugs with non hematological side effects (e.g., cardiotoxicity of anthracyclines or neurotoxicity of methotrexate). The target for such drug side effects need to be determined before the proper dose unit can be selected. A review of available data shows that for at least some non hematological side effects BSA does not offer the proper prescription unit. The historical justifications for BSA as dose unit are re-examined (simplicity, correlation with blood volume, correlation with area under the curve) and considered invalid. The ultimate long term improvements from better prescription methods for cancer chemotherapeutic agents are less normal tissue side effects and better tumor control. The indiscriminate use of BSA as a universal dose unit for cancer chemotherapy would prevent such improvements and is discouraged. Instead, drug doses are to be expressed in units that correlate with dose limiting normal tissue cells.

Adult↗

PubMed1987

Concurrent measurements of blood flow and transcapillary transport in xenotransplanted human gliomas in immunosuppressed rats.

Neonatal Fischer 344 rats were immunosuppressed with antithymocyte serum and later were given an injection intracerebrally of cells from the human glioma permanent line D-54MG. Symptomatic tumor-bearing rats were studied with double-label quantitative autoradiography to concurrently measure blood flow and a unidirectional blood-to-tissue transfer constant (K) for alpha-aminoisobutyric acid (AIB). A net extraction fraction (En) was calculated from the measured values for blood flow and K. Mean whole tumor blood flow was 53.5 +/- 4.9 ml/100 g/min (mean +/- SEM), which was significantly less than the blood flow to the tumor-free cortex (198 +/- 15.5 ml/100 g/min) but not significantly different from the blood flow in the tumor-free corpus callosum (50.6 +/- 4.3 ml/100 g/min). Mean whole tumor K-value for AIB was 5.8 +/- 0.5 ml/100 g/min, approximately 30 times the K-value for tumor-free brain. The calculated mean whole tumor En was 0.2 +/- 0.09, nearly 100 times the value for the tumor-free brain. Regionally, blood flow was lower in the tumor center and higher in its tumor periphery, although the difference was not significant. Both K- and En-values were significantly higher for the tumor center and decreased radially for the areas from center out. The values for K and En of AIB in the D-54MG gliomas are the highest of any experimental brain tumor model studied to date and indicate that in some tumor regions in this model, blood-to-tissue transport of the water-soluble compound AIB may be dependent on blood flow as well as on the permeability-surface area product of the tumor capillaries.

Aminobutyrates↗

PubMed1984

Murine sarcoma virus-induced brain tumors. Concurrent measurements of blood flow and transcapillary transport.

Intracerebral inoculation of Murine Sarcoma Virus (MSV) into rats induces highly vascular brain tumors. Blood flow, F, and a unidirectional blood-to-tissue transfer constant, K, were measured concurrently in 16 separate brain tumors in 13 rats. Regional measurements of F and K were obtained using double-label quantitative autoradiography with 131I-iodoantipyrine, 14C-alpha aminoisobutyric acid, and computerized microdensitometry with image analysis. Regional tissue extraction fractions (E) were calculated for different brain and tumor regions. The following observations were made: intracerebral inoculation of MSV in rats of different ages produced a single histologic tumor type (angiosarcoma), although tumor yield decreased and latency increased when older rats were inoculated; whole tumor blood flow values averaged 63.9 +/- 20.9 (SD) ml hg-1 min-1, less than F of tumor-free gray matter; the mean value of the transfer constant was 1.19 +/- 0.84 ml hg-1 min-1, 5 times the value in contralateral tumor-free brain; moderate regional variation of F and K values were observed within each tumor, with increased K values extending into the regions of brain around tumor; mean extraction fractions (E) of AIB for whole tumor were low (range = 0.0021 to 0.08), with a distinct and decreasing gradient from tumor center to BAT; there was poor correlation between F, K and E values, and tumor histology, including regions that microscopically appeared highly vascular; in most regions of the MSV-induced brain tumors, capillary permeability and/or surface area seem to be determinant in blood-to-tissue transport processes.

Aminoisobutyric Acids↗