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Biomedical subjects

T L Avery

Publications and source records attributed to T L Avery.

At least 37 records · Page 2Linked to original sources
PubMed1984

Improved synthesis and antitumor activity of 2-bromo-2'-deoxyadenosine.

A more convenient synthetic route to 2-bromo-2'-deoxyadenosine (5) is reported, and results indicating significant antitumor activity of 5 against three murine tumors (L1210 leukemia, B16 melanoma, and M5076 ovarian carcinoma) are presented. The antitumor activity is very schedule dependent, being much greater when the drug is given q 3 h (X8) every 3rd or 4th day than when given by single daily administration. Toxicity of 5 for the tumor-bearing host is also very schedule dependent. Thus, on the q 3 h schedule of administration, a greater cumulative dose is tolerated by the host, and the therapeutic effectiveness of 5 is enhanced accordingly.

Animals↗
PubMed1983

2'-O-nitro-1-beta-D-arabinofuranosylcytosine. A new derivative of 1-beta-D-arabinofuranosylcytosine that resists enzymatic deamination and has antileukemic activity.

To overcome the susceptibility of the anticancer drug 1-beta-D-arabinofuranosylcytosine (ara-C) to enzymatic deamination, and hence deactivation, we prepared the 2'-O-nitro-1-beta-D-arabinofuranosylcytosine (termed nitrara-C) and evaluated it for biological activity. Nitrara-C was resistant to enzymatic deamination and inhibited the proliferation of several strains of human leukemic T and B lymphoblasts grown in culture. Moreover, it substantially extended the life spans of mice with L1210 leukemia. Studies with ara-C-resistant human leukemic lymphoblasts deficient in deoxycytidine kinase activity disclosed that the inhibitory activity of the new compound depends on its phosphorylation.

Animals↗
PubMed1982

VM-26 with prednisone and vincristine for treatment of refractory acute lymphocytic leukemia.

Fifty-six children with refractory acute lymphocytic leukemia (ALL) were assessed for remission-induction responses to VM-26 (250 mg/m2 per week) in combination with prednisone (40 mg/m2 per day) and vincristine (1.5 mg/m2 per week). Each child had been treated intensively with steroids, vincristine, daunorubicin and L-asparaginase. In fact, all patients had failed to respond to previous reinduction therapy with prednisone-vincristine or had relapsed while receiving vincristine. Our intent in this study was to test whether or not addition of VM-26 to prednisone-vincristine would overcome clinical resistance to these established agents. Complete remissions were induced in 17 patients (0.30) over 4 to 6 weeks. Five of these children, all clinically unresponsive to prednisone-vincristine alone, had complete remissions that lasted longer than 1 year; two remain in remission for 2 1/2 years and both are now off therapy. Myelosuppression, the most serious treatment complication, was documented in 20 of 26 evaluable patients. The median time to recovery of normal marrow function was 15 days. These results demonstrate further the potential of VM-26 in combined-drug treatment of refractory ALL. Whether the effectiveness of this combination represents potentiation of prednisone and vincristine activity by VM-26 or some other, as yet unidentified interaction, remains to be determined.

Adolescent↗
PubMed1980

VM-26 and cytosine arabinoside combination chemotherapy for initial induction failures in childhood lymphocytic leukemia.

Combination chemotherapy with VM-26 and ara-C was given to 14 children with acute lymphocytic leukemia who had not responded to initial treatment with prednisone, vincristine, daunomycin, and asparaginase. Nine of these patients had also received ara-C. At diagnosis, five children were classified as having standard prognostic features and nine as being at high risk for treatment failure. The drug combination was administered by vein twice a week for four weeks at dosages of 165 mg/m2 for VM-26 and 300 mg/m2 for araC. Nine complete remissions, five in patients with high-risk leukemia, were induced with acceptable toxicity; all 9 subsequently were given continuation therapy with oral mercaptopurine and methotrexate. Four of the 9 patients have relapsed at 2--21 months. All treatment was stopped in 2 patients after 30 months of complete remission. Combinations of VM-26 and ara-C represent an alternative remission induction treatment for patients who fail to attain initial remission with agents of established effectiveness. These agents may especially benefit patients with prognostic features indicating a high risk of treatment failure.

Adolescent↗
PubMed1980

Combined VM-26 and cytosine arabinoside in treatment of refractory childhood lymphocytic leukemia.

On the basis of previous findings at this institution, VM-26 and Cytosine Arabinoside (ara-C) were used in combination to treat 33 children with refractory acute lymphocytic leukemia (ALL). Chemotherapy was given by vein twice a week for four weeks at dosage of 300 mg/m2 for ara-C and 50, 75, 110, 165, or 200 mg/m2 for VM-26. Ten marrow remissions (nine complete and one partial) were induced, with hypotension (2/33) and bone marrow hypoplasia (20/33) the most significant side effects observed. Therapeutic responses were obtained with each dosage of VM-26 except 75 mg/m2; myelosuppression developed at all dosages, being most prolonged at 200 mg/m2. Ten of the 23 non-responders did not complete their planned courses of therapy. The significance of this information is that combinations of VM-26 and ara-C were effective in patients who were either in late stages of their leukemia or had never achieved an initial remission. All had been previously treated with prednisone, vincristine, daunomycin and L-asparaginase. In addition, seven of the 10 responders had previously received ara-C in other drug combinations. The use of VM-26 and ara-C in combination may be warranted for newly diagnosed patients who are at high risk for treatment failure with first-line drugs.

Adolescent↗
PubMed1977

Continuous negative chest-wall pressure therapy for assisting ventilation in older children with progressive respiratory insufficiency.

Continuous negative chest-wall pressure (CNP) was used to assist ventilation in 14 children, 6 months to 14 years of age, who had progressive respiratory insufficiency caused by diffuse bilateral alveolar disease. Before the start of CNP therapy, each child had a respiratory rate greater than 50/min, arterial oxygen tension (PaO2) less than 70 mmHg (FIO2 greater than or equal to 50%), and arterial carbon dioxide tension (PaCO2) less than 45 mmHg. The mean intrapulmonary right-to-left shunt was 28.7 +/- 3.8%. Within 6 hours after therapy was started, PaO2 increased from 55.4 +/- 15.9 to 81.6 +/-17.7 mmHg (p less than 0.005). This improvement was sustained and within 24 hours permitted a decrease in fractional concentration inspired oxygen (FIO2) from 51.8 +/- 6.2 to 41.0 +/- 8.4% (p less than 0.001) and in respiratory rate from 78.1 +/-23.0 to 56.4 +/- 21.3 (p less than 0.01). There was a concomitant decrease in intrapulmonary right-to-left shunt. Four of the 14 patients developed pneumothorax that was successfully decompressed. Ten patients survived. These observations establish CNP therapy as an effective means of improving arterial oxygenation in spontaneously breathing older children. Of added significance, this mode of therapy eliminates the need for endotracheal intubation and prolonged use of muscle relaxants and sedatives. It also minimizes exposure to high FIO2, thereby minimizing the hazards of pulmonary oxygen toxicity.

Adolescent↗
PubMed1977

Management of severe respiratory insufficiency due to Pneumocystis carinii pneumonitis in immunosuppressed hosts: the role of continuous negative-pressure ventilation.

Continuous negative-pressure therapy was used to assist ventilation in 19 spontaneously breathing patients, 6 months to 17 years of age, who developed progressive respiratory insufficiency (arterial PO2 less than 70 mm Hg despite a fraction of inspired O2 larger than or equal to 50 per cent) due to Pneumocystis carinii pneumonitis. Within 1 hour of therapy, arterial PO2 increased from a mean +/- SE of 61.9 +/- 3.7 to 75.4 +/- 7.0 mm Hg (P less than 0.05) and, by 6 hours, to 79.9 +/- 4.7 mm Hg (P less than 0.005). In the 14 survivors, these improvements were sustained and, within 24 hours, permitted a decrease in inspired O2 concentration from a mean +/- SE of 50.4 +/- 1.2 per cent to 40.1 +/- 1.6 per cent (P less than 0.005). By contrast, in nonsurvivors, O2 requirements could not be decreased significantly despite increases in negative pressure. Improvements in arterial oxygenation were associated with decreases in alveolar-arterial PO2 differences in all patients; however, significant decreases occurred only with pressures of -8 to -12 cm H2O. Higher negative pressures were ineffective and usually produced pulmonary air leak. Since the introduction of continuous negative-pressure therapy as a means of assisting ventilation in management of progressive respiratory insufficiency, the over-all survival rate among patients with Pneumocystis carinii pneumonitis at this institution has increased from 69 to 89 per cent.

Adolescent↗
PubMed1977

Adriamycin and cyclophosphamide in combination chemotherapy of L1210 leukemia.

Combination of cyclophosphamide and adriamycin, encompassing a wide range of dosages, were administered on five different schedules to C57BL/6J X DBA/2J F1 female mice inoculated i.p. with L1210 ascites tumor cells. Among the resulting 85 treatment groups, the mean postinoculation survival of mice that died with tumor was 11.4 to 51.3 days; this represented increases of 62 to 628% over the survival of untreated controls. In some groups, tumor cells were eradicated in 9 of 10 treated mice. By contrast, neither drug given alone cured leukemic mice or extended their survival beyond controls by more than 96%. Adriamycin and cyclophosphamide were most effective when administered simultaneously on Day 1; additional treatment with adriamycin on Days 4 and 7 produced a significant increase in the survival of mice that died with tumor, but this regimen did not increase the incidence of cures. Combination therapy with these agents reduced the cytotoxic response of the host to subsequently inoculated L1210 cells. The pronounced therapeutic effectiveness of this drug combination is attributed to a true potentiation of the independent oncolytic action of each agent.

Animals↗