PubMed Health⌕ Search

Biomedical subjects

D V Jackson

Publications and source records attributed to D V Jackson.

100 records · Page 6Linked to original sources
PubMed1980

Pharmacokinetics of vincristine in the cerebrospinal fluid of subhuman primates.

Adult rhesus monkeys were given 2-mg/sq m i.v. bolus injections of radiochemically pure tritiated vincristine (VCR). Simultaneous specimens of blood and cerebrospinal fluid (CSF) were sampled from 5 min to 72 hr following injection. CSF was obtained from Ommaya reservoirs which had been implanted s.c. in each monkey. VCR and its metabolic and/or decomposition products rapidly entered the CSF producing low concentrations in this fluid; 5 min following injection, the concentration of VCR was 2.3 nM, whereas approximately a 100-fold greater concentration (203.8 nM) was attained in the plasma. Throughout a 3-day period of observation, constant, low levels of VCR and its metabolic and/or decomposition products (2.3 to 5.7 nM) were maintained in the CSF. The principal form of VCR present in the CSF 1 hr or more after i.v. injection was a water-soluble metabolite and/or decomposition product(s). Although the levels achieved in the CSF are unlikely to be lethal to tumor cells, the finding of persistent low concentrations of VCR and its metabolic and/or decomposition products in the CSF indicates prolonged exposure of neural tissue which might result in neurotoxicity, particularly cumulative neurotoxicity following multiple doses of VCR.

Animals↗
PubMed1979

Cytotoxic thresholds of vincristine in a murine and a human leukemia cell line in vitro.

L1210 murine leukemia and CEM human lymphoblastoid leukemia cells were exposed to vincristine sulfate in vitro. The response of these cell lines to this agent was measured by the colony-forming ability of L1210 cells in soft agar and inhibition of growth of CEM in suspension culture. Incremental increases of vincristine concentrations in excess of 2 x 10(-9) M produced a progressive reduction of survival of L1210 cells and suppression of CEM growth under the condition of constant drug exposure. A maximum cytotoxic effect was reached with drug concentrations between 10(-8) and 10(-7) M. When L1210 cells were exposed to vincristine for a variable length of time ranging from 0.5 to 24 hr, 10(-7) M produced a noticeable cytotoxic effect following an incubation of only 30 min. A 50% cell kill of L1210 cells and a 50% reduction of CEM cell growth were produced by 10(-7) M following a 1- to 3-hr period of exposure; 6 to 12 hr were required to produce a similar effect at a vincristine concentration of 10(-8) M. Therefore, the antitumor effect of vincristine is critically dependent on both concentration and duration of exposure. These data suggest the possibility that the effectiveness of vincristine as an antitumor agent could be enhanced if methods are developed to prolong exposure of neoplastic tissues for longer periods of time than currently produced by conventional methods of administration.

Animals↗
PubMed1978

Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial.

Adriamycin is of noteworthy efficacy in the treatment of metastatic breast cancer. Its role in combination regimens is under investigation. One hundred seventy-five women with advanced breast cancer were entered into a prospectively randomized trial comparing two five-drug regimens. Regimen CMFVP consisted of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), vincristine (V), and prednisone (P). Regimen CAFVP was identical but substituted Adriamycin (A) for methotrexate. Twenty-seven patients were disqualified; 148 were evaluable. With CMFVP the complete response rate (CR) was 11%, and the partial response rate (PR) was 46%; with CAFVP, CR was 13% and PR was 45%. Duration of response tended to be slightly longer for patients on the Adriamycin arm. The median survival for CR and PR patients with CMFVP was 20.2 months, which was shorter (p = .07) than the 33 month median survival with CAFVP. Although statistical significance was not reached at the 5% level, the increased survival of responders on the Adriamycin regimen supports the data of other studies which suggest that first line combination chemotherapy in advanced breast cancer should include Adriamycin.

Antineoplastic Agents↗
PubMed1978

Biliary excretion of vincristine.

A patient with pancreatic carcinoma and a choledochal T tube was given tritiated vincristine sulfate ([3H]-VCR) intravenously. Peak biliary excretion occurred in 2 to 4 hr and this sample contained 9.7% of the injected radioactivity. The first 24-hr bile sample contained 21.7% of the dose and 76.4% of the cumulative 72-hr biliary excretion. During a 3-day period of observation, 4.2%, 45.6%, and 49.6% of the excreted radiolabel was present in the feces, urine, and bile, respectively. Products of VCR metabolism and decomposition appeared in the bile rapidly; only 46.5% of the drug was present in the parent form in the 2-hr collection. Since significant amounts of these products were also identified in control specimens of bile, blood, plasma, and buffer alone after brief periods of incubation, the origin and nature of the species appearing in the bile remain unclear. Observing the fecal route to be the major source of elimination of radiolabel following intravenous injection of [3H]-VCR in our patients previously, we now conclude the biliary system to be the principal route of excretion of VCR and its products. Hepatic dysfunction might therefore alter elimination kinetics and increase the exposure to VCR and its products which might augment toxicity and require dose modification.

Bile↗
PubMed1977

Prophylactic cranial irradiation in small cell carcinoma of the lung. A randomized study.

Twenty-nine patients with small cell carcinoma of the lung and without evidence of brain metastasis were randomized into two treatment groups consisting of 14 patients who received prophylactic cranial irradiation (PCI) and 15 who received none (non-PCI). All patients were treated with irradiation of the primary lesion and concomitant chemotherapy. The response rate and median survival of the two groups were not significantly different: 93% and 7.2 months in the non-PCI; 86% and 9.8 months in the PCI; P larger than or equal to .05. Brain metastasis occurred in 0/14 patients in the PCI and 4/15 in the non-PCI (P less than or equal to .05) and was the cause of major neurologic disability in each. Although PCI did not improve response rate or survival, brain metastasis with its attendant neurologic complications was effectively prevented.

Adult↗
PubMed1977

Lymphographic and echographic findings in angioimmunoblastic lymphadenopathy.

Four patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) had lymphograms that did not show a consistent radiographic pattern. Instead, a spectrum of radiologic changes ranging from a moderate increase in lymph node size with slight "foaminess" to total nonopacification was observed. One patient with this disorder had gray-scale echograms that showed enlarged anechoic lymph nodes. The findings in this small group of patients with AILD are indistinguishable from the radiologic and echographic changes seen in malignant lymphoma.

Aged↗
PubMedDate not supplied

Phase I study of high-dose cytarabine and cisplatin in patients with advanced malignancy.

Nineteen patients with advanced malignancy participated in a phase I trial of high-dose cytarabine (ara-C) and cisplatin in combination. Dose and schedule were based on laboratory data indicating synergy for concurrent use of these drugs. Cisplatin (100 mg/m2) was administered during the 2nd and 3rd hours of a 3-hour ara-C infusion. The ara-C dose was escalated in subsequent patients following a starting dose of 1 g/m2. Two brief responses were noted. The study was terminated prematurely due to protracted (several weeks) nausea, occasional vomiting, and severe lassitude.

Adult↗
PubMedDate not supplied

Pharmacokinetics of vincristine infusion.

Using a sensitive radioimmunoassay, serial blood concentrations of vincristine were measured in 11 patients with refractory malignancies receiving infusions of vincristine at three dose levels: 0.5, 0.75, and 1.0 mg/m2 daily for 5 days. The pharmacokinetics of vincristine infusion were compared to pharmacologic data obtained from four patients who received conventional iv bolus injections of 2 mg of vincristine. Whereas rapid decline of blood levels was seen following iv bolus injection, with concentrations of vincristine approaching 10(-9) M by 48-72 hours, vincristine infusions of 0.5, 0.75, and 1.0 mg/m2 daily for 5 days consistently resulted in blood concentrations greater than 10(-9) M during the treatment period. Similarly, areas under the concentration curve were greater in patients receiving infusions compared to bolus injections of vincristine. Antitumor responses in patients receiving vincristine infusions were observed after failure to respond to iv bolus injections. These data demonstrate the ability of infusion therapy to sustain blood concentrations of vincristine in man beyond that seen with conventional administration and suggest the possibility of improved therapeutic efficacy with this agent by use of infusion techniques.

Adult↗
PubMedDate not supplied

Diltiazem-associated thrombocytopenia.

Nine days after starting diltiazem therapy for new-onset atrial fibrillation, a patient's platelet count had diminished to 61 x 10(3)/mm3, and 2 weeks later the nadir was reached at 23 x 10(3)/mm3. No hypersensitivity reaction otherwise was noted, and other hematologic values were unaffected. The patient's platelet counts were not affected by platelet transfusions. Bone marrow examination showed normal to increased numbers of megakaryocytes, suggesting peripheral destruction. After discontinuing diltiazem and administering high-dose immunoglobulin infusions, the platelet count returned to normal. This case suggests an immune-mediated cause for thrombocytopenia after exposure to diltiazem.

Aged↗