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Biomedical subjects

D C Wright

Publications and source records attributed to D C Wright.

101 records · Page 6Linked to original sources

Retrograde state dependent learning.

Sodium pentobarbital administered intravenously after acquisition in a one-trial passive avoidance task results in state dependent (drug dissociated) learning in male albino rats. Findings have methodological implications for drug-based research and theoretical implications for drug discrimination studies. Predictions based on a stimulus generalization hypothesis are not supported, whereas those based on an information storage hypothesis are supported.

Animals↗

Cadmium absorption and tissue distribution in rats provided low concentrations of cadmium in food or drinking water.

Tissue Cd levels were determined 1, 2, 4, 8, and 12 wk after weanling rats were provided with food or water containing 1-1000 ng/g Cd as 109CdCl2. No differences in growth rate or organ weight were observed over the concentration range tested. Kidney accumulated the highest concentration of Cd, followed by liver with values one-third to one-fourth those found in the kidney. Liver, however, accounted for 35-55% of the total body burden, while kidney contained only 35-45%. Cd concentrations in the various tissues increased with time and the Cd concentration of the food or water. The percentage of the ingested dose absorbed in a given time was relatively constant over the tested Cd concentration range. However, for each metal concentration, the percent of Cd absorbed decreased with exposure time. Regression analysis established that female rats accumulated Cd at a higher rate and retained a greater percentage of the ingested Cd than did male rats and that tissue concentrations were higher in rats exposed to Cd in the water. The differences in tissue Cd levels are probably related to proportionally higher metal intake by females and to higher intake from water than food at equivalent concentrations. It is uncertain whether the greater retention of ingested Cd by females is due to more efficient absorption or a reduced rate of excretion of the metal.

Animals↗

Sequential MR studies of intracerebral hematomas in monkeys.

It is well recognized that the MR appearance of intracranial bleeding changes with the age of lesion. It is also well known that hemoglobin in stagnating blood undergoes oxidation to methemoglobin, a substance that lowers the relaxation times of surrounding water protons. To study these phenomena in a controlled way, about 3 ml of blood was injected into the right frontal lobe of two rhesus monkeys, and they were scanned sequentially for up to 2 months in a Picker NMR scanner (Bo = 0.25-0.5 T). The image intensity of the blood changed during the first week, consistent with the lowering of T1 and T2. On the inversion-recovery scans the initial appearance of the blood was less bright than was the contralateral white matter, reversing after 3-5 days. The opposite was true on spin-echo images. T1 and T2 values were calculated for all images. In parallel experiments, several milliliters of freshly drawn blood was placed in test tubes and relaxation times were measured in a bench-top analyzer at 0.25 T over a period of 10 days. The relaxation times dropped markedly, at a rate that depended on sterility, temperature, etc., closely approaching the expected result for complete conversion of hemoglobin to methemoglobin. Ten blood samples with different methemoglobin concentrations were prepared by adding varying doses of sodium nitrite. The change in 1/T1 was found to be roughly proportional to the methemoglobin concentration for values up to 40%, and the initial slope was consistent with published data.

Animals↗

Collaborative Behavioral Teratology Study: results.

Behavioral measures used in the Collaborative Behavioral Teratology Study (CBTS) were negative geotaxis (PNDs 7-10), olfactory discrimination (PNDs 9-11), auditory startle habituation (PNDs 18-19 and 57-58), 1-hr activity (PNDs 21, 60, 100 and 120), 23-hr activity (PND 100), activity following a pharmacological challenge (PND 120), and an operant, discrete trial visual discrimination task. Maternal and offspring body weights and the appearance of certain physical landmarks of development were also monitored. The design of the CBTS allowed evaluation of the reproducibility and detection sensitivity of these behavioral test methods, as well as the impact of early testing experience on later behavioral assessment, offspring sex differences in response levels and variability, and the contribution of litter-to-litter and animal-to-animal variation to behavioral measures in a standardized test protocol. The results obtained in this test system are discussed in relation to each of these factors and to the degree of overt toxicity obtained using prenatal treatment with 0, 0.5 or 2.0 mg/kg d-amphetamine sulfate, SC, on gestation days 12-15 (Study 1) or methylmercuric chloride, 0, 2.0 or 6.0 mg/kg by gavage, on gestation days 6-9 (Study 2).

Age Factors↗

Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors.

Fifty-eight patients harboring recurrent malignant brain tumors were evaluated. CCNU (110 mg/m2) was administered on Day 1, procarbazine (60 mg/m2) was administered daily for 14 days beginning on Day 8, and vincristine (1.4 mg/m2) was administered on Days 8 and 29 of each 6-week cycle of therapy. Therapy was continued until tumor progression was documented. Before each course, a neurologic examination was performed and radionuclide and computerized tomographic scans were obtained. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Of the 46 patients harboring recurrent malignant gliomas, 12 (26%) responded to therapy, 18 (39%) had tumor progression, and 16 (35%) had disease stability. Nineteen of the 46 patients were not previously treated with another form of chemotherapy: eight (42%) responded to therapy, eight (42%) had disease stability, and only three (16%) had early tumor progression. The median time to tumor progression was 26 weeks for patients responding to therapy or having disease stability. Approximately 30% of the patients were alive without evidence of tumor progression at 1 year. Evaluated by time to tumor progression and rate of tumor response or stabilization, this combination was similar to the BCNU-5-fluorouracil combination used for patients harboring recurrent malignant glioma.

Brain Neoplasms↗