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D Gangji

Publications and source records attributed to D Gangji.

33 records · Page 2Linked to original sources

Probenecid inhibition of methotrexate cytotoxicity in mouse L1210 leukemia cells.

The effect of probenecid on methotrexate cytotoxicity has been measured using mouse L1210 leukemia cells in vitro. Cytotoxic effects were measured using a soft agar cloning technique. Cell exposure to varying concentrations of methotrexate at fixed concentrations of probenecid resulted in increased cell survival when compared with exposure to methotrexate alone. Cell exposure to a fixed concentration of methotrexate and varying concentrations of probenecid showed this effect to be dependent on the concentration of probenecid. Intracellular methotrexate concentrations were unchanged by the presence of probenecid. However, there was an effect of probenecid on progression of cells through the cell cycle which would tend to decrease the number of cells susceptible to the cytotoxic effects of methotrexate.

Animals↗

Rectus sheath hematoma mimicking acute splenic disease.

In patients with hematological malignancies and splenomegaly, acute abdominal pain in the left upper quadrant is highly suspicious of splenic disease (i.e., hematoma, infarction, or rupture). We report the case of a patient with chronic myelogenous leukemia and splenomegaly who presented an unusual abdominal condition causing pain in the left upper quadrant, with a clinical presentation mimicking acute splenic disease. The diagnostic dilemma was resolved by ultrasonography, demonstrating a rectus sheath hematoma.

Abdominal Muscles↗

Cerebrospinal fluid levels of 2'-deoxycoformycin after systemic administration in monkeys.

2'-Deoxycoformycin (DCF) is an inhibitor of the enzyme adenosine deaminase (ADA) and has shown promise as an antileukemia agent. For the assessment of the extent to which systemically administered DCF crosses into the central nervous system (CNS), rhesus monkeys were given iv boluses of DCF. Simultaneous blood and cerebrospinal fluid (CSF) samples were assayed for DCF levels at times ranging from 10 minutes to 6 hours after the drug was given. Average peak CSF drug levels of 5.5 X 10(-8) M and 3 X 10(-7) M were reached 1 1/2 - 2 hours following injections of 0.25 and 1.0 mg DCF/kg, respectively. The ratio of peak CSF to simultaneous plasma levels was 1 to 10. Data obtained from a patient who had acute lymphocytic leukemia and who was given iv DCF were comparable. Drug levels achieved within the CSF following iv administration of 0.25 mg DCF/kg are similar to those previously demonstrated to inhibit ADA. These results may be important both for understanding DCF-related CNS toxicity and for designing combination chemotherapy with DCF.

Animals↗

Pharmacokinetic study of cerebrospinal fluid penetration of cis-diamminedichloroplatinum (II).

The ability of cis-DDP and several analogs to enter the CSF was investigated in rhesus monkeys that had subcutaneously implanted Ommaya reservoirs connected to catheters in each monkey's fourth ventricle. Plasma and CSF samples were analyzed for platinum content by atomic absorption spectroscopy. Plasma platinum curves were biphasic with a very slowly declining terminal phase. CSF platinum curves rose to maximum concentrations 30-40 min after an IV bolus injection and declined mono-exponentially (T 1/2 = 60 min) without displaying a detectable slow terminal phase. cis-DDP given as an IV bolus of 1.5 mg/kg or 3.0 mg/kg produced peak CSF concentrations of 0.35 and 0.78 microM platinum. The ratio of CSF platinum:plasma platinum never exceeded 0.04. When cis-DDP at 3.0 mg/kg was given as a 2- or 7-h infusion, the peak CSF concentrations were 0.28 and 0.17 microM platinum, respectively. The total CSF exposure, measured as concentration X time, was the same for bolus and for 2- and 7-h infusions. Studies with analogs showed that neither malonato 1,2-diaminocyclohexane platinum (II) nor 4-carboxyphthalato 1,2-diaminocyclohexane platinum (II) had better CSF penetrance than cis-DDP. Sulfato 1,2-diaminocyclohexane platinum (II) could not be detected in the CSF. The ratio of CSF platinum:plasma platinum was never greater tha 0.02-0.03 for any of the analogs.

Animals↗

Phenytoin-misonidazole: possible metabolic interaction.

Following iv administration of misonidazole, evidence of decreased plasma half-life (3.8 hours versus 9.1 hours +/- 0.8 [SD] in eight other patients studied) and increased metabolism was observed in a patient receiving continuous phenytoin therapy.

Drug Evaluation↗