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L Booker

Publications and source records attributed to L Booker.

12 recordsLinked to original sources
PubMed1992

The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial.

Laboratory studies, and one previous uncontrolled trial, have suggested that retinoids may reverse bronchial atypia, a putatively premalignant condition. Sputum sampling is a simple, non-invasive method of assessing atypia. Smokers with at least a 15 pack-year history were screened for sputum atypia. One hundred and fifty subjects' were randomised to receive the synthetic retinoid etretinate 25 mg orally or identical placebo daily for 6 months. Compliance was measured by performing pill counts and serum sampling every 2 months for etretinate levels. The outcomes assessed were, improvements in sputum atypia and toxicity. At baseline there was no significant difference between the two groups with respect to gender, smoking history or extent of atypia. Four of 75 subjects on etretinate and six of 75 on placebo dropped out before 6 months. Compliance as measured by pill counts and etretinate levels was high. Eighty-six per cent of subjects on etretinate took 90% or more of their prescribed medication and etretinate was detected in 245 of 264 samples. By contrast etretinate was detected in only six of 266 samples in the control group and probably did not represent true contamination. After 6 months on etretinate there was no difference in the degree of atypia between the two treatment arms. Toxicity was mild in both groups with considerable placebo effect noted. Etretinate, at the dose used in this study, had no impact on sputum atypia as detected by sputum sampling.

Administration, Oral↗
PubMed1991

Optimal conditions for immunohistochemical determination of the in vitro DNA synthesis labelling index with bromodeoxyuridine in head and neck cancer.

The in vitro DNA synthesis labelling index was assessed immunohistochemically in 24 freshly obtained specimens of head and neck cancer using bromodeoxyuridine (BrdUrd) as the DNA precursor to determine the influence of BrdUrd concentration on labelling index (LI). Initially, tumour fragments were incubated in varying concentrations of BrdUrd from 2 to 100 microM for 2 h, and BrdUrd was detected with an anti-BrdUrd monoclonal antibody using immunoperoxidase labelling. There was a dose-response gradient with mean LI varying from 1.6% at 2 microM BrdUrd to 8.8% at 100 microM. The concentration-response gradient best fit a quadratic model when LI was plotted against log BrdUrd concentration (r = 0.65, P less than 0.0001). Eleven additional tumours were then studied to determine whether LI increased for BrdUrd concentrations above 100 microM. The mean LI at 125 microM and at 150 microM in these 11 tumours did not differ from the value at 100 microM, suggesting a plateau at this level. The gradient effect accounted for 17% of the variance in LI, while 60% of the variance was explained by between tumour differences. Within individual tumours, three response patterns were observed: (i) LI rose at a constant rate to the highest concentration tested (n = 8), (ii) the LI plateaued or declined at high BrdUrd concentrations (n = 6); and (iii) there was a biphasic slope slope in which the rate of rise in the LI increased at the higher BrdUrd concentrations (n = 2). The data show that BrdUrd concentration is an important variable in the immunohistochemical assessment of the in vitro LI in head and neck cancer.

Biopsy↗
PubMed1990

Chemoprevention for lung cancer--evidence for a high degree of compliance.

Studies of treatment efficacy are important for the development of cancer chemoprevention strategies. Recruitment aims for motivated, compliant subjects. The Concerned Smoker Study targets smokers with at least a 15-pack-year history and bronchial atypia on sputum sampling. Subjects receive etretinate 25 mg daily or identical placebo and are followed for 6 months. Compliance was monitored by assessing timely return for follow-up visits, return of monthly sputum samples, pill counts, and serum etretinate levels. Contamination, in the control group, was assessed by measuring etretinate levels. With half of the subjects having completed the study, this report assesses compliance: 88% follow-up visits occurred on schedule with only 9 missed visits of a possible total of 380; 443 (97.1%) of 456 possible sputum samples were returned. Pill counts indicated a high degree of compliance which was supported by the serum etretinate levels. Contamination was insignificant. The results suggest a very high degree of compliance. Only minor protocol changes will be required.

Etretinate↗
PubMed1989

Etretinate blood levels in monitoring of compliance and contamination in a chemoprevention trial.

We measured serum etretinate to monitor compliance in an ongoing chemoprevention trial in which heavy smokers are randomized to either etretinate or placebo orally for 6 months. Blood is collected for determination of etretinate levels before treatment and then at 2, 4, 8, 16, and 24 weeks after randomization. The monitoring strategy was assessed by interim evaluation. There were 276 posttreatment samples available from 75 randomized subjects of whom 36 received etretinate and 39 placebo. The mean coefficient of variation for the internal standard retinyl acetate in serum was 4.16% for the high-pressure liquid chromatography method used. Among positive samples, the mean etretinate concentration was 25.7 ng/mL (SD, 23.4). Of the 131 samples obtained from subjects randomized to etretinate, 120 or 91.6% had detectable levels compared with 4 of 145 or 2.8% placebo samples. Among the 36 subjects given etretinate, at least one positive test occurred. In 27 of these 36 participants, etretinate was detected in every sample obtained. In the other nine, the absence of drug could be explained by pill counts or a history of discontinuation of treatment for six. Among the 39 subjects given placebo, the four positive samples were from four individuals, all of whom were negative on three other occasions. These data confirm the usefulness of the monitoring system we used and indicate that compliance and/or contamination will not be major problems in this trial.

Chromatography, High Pressure Liquid↗
PubMed1986

Influence of the poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide on macrophage and granulocyte differentiation of HL-60 cells.

We investigated the influence of the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide (ABA) on induction of phenotypic markers of granulocyte differentiation by retinoic acid and markers of macrophage differentiation by TPA in HL-60 cells. The differentiation of HL-60 cells towards the granulocyte lineage was assessed by hexose monophosphate shunt activity, proportion of cells capable of reducing NBT dye, and the appearance of recognizable neutrophils and bands. The effect of ABA and retinoic acid on NBT dye reduction and appearance of mature neutrophils and bands was synergistic, whereas the effects of these agents on hexose monophosphate shunt activity were additive. The differentiation inducing capacity of ABA in the presence of retinoic acid was dose-related. The influence of ABA on TPA-induced markers of macrophage differentiation was assessed by determining the proportion of adherent cells produced after treatment and by measuring acid phosphatase activity in the adherent cell fraction. In the presence of ABA, the number of cells adhering to plastic declined after day 2 of exposure to TPA, and acid phosphatase activity in adherent cells was inhibited fourfold (p = 0.01). The influence of ABA on the phenotypic markers of granulocyte and macrophage differentiation was detectable at concentrations that were not cytotoxic. The influence of ABA on HL-60 differentiation is similar to that previously reported for human bone marrow CFU-GM. Our data suggest that poly(ADP-ribose) polymerase plays a role in differentiation of HL-60 cells and that HL-60 might provide a useful model for evaluating control mechanisms involved in the differentiation of CFU-GM.

Acid Phosphatase↗
PubMed1985

Dogs bites.

Explore the source record for details and available documents.

Adolescent↗
PubMed1985

Differential calcium leucovorin protection of human lymphoid cell lines from methotrexate.

Human lymphoid cell lines were studied for leucovorin requirements to protect from methotrexate (MTX)-induced growth suppression. Over a 72h continuous exposure leucovorin provided better protection to the cell lines LAZ-007 and RAJI than to the cell lines CCRF-CEM and MOLT-4. The lower leucovorin requirement for LAZ-007 protection versus CCRF-CEM was also seen over a 3h exposure period in which leucovorin protection was assessed by measuring its effect on MTX-induced suppression of 3H-deoxyuridine incorporation into acid-precipitable material. Growth experiments with addition of hypoxanthine or thymidine did not abolish differential protection, suggesting that the phenomenon is not related to selective differences in the tolerance of these cells to an MTX-induced purineless or thymineless state. Preloading of cells with calcium leucovorin caused an identical shift of the CCRF-CEM and LAZ-007 MTX dose - response curves, suggesting that differential catabolism of leucovorin does not contribute to differential protection. The same degree of differential protection was observed for 5-methyltetrahydrofolate as for leucovorin, suggesting that differences in the metabolism of leucovorin do not contribute to differential protection. To elucidate the mechanism of differential protection the influence of leucovorin on [3H]MTX transport and polyglutamylation were studied. Although the Km(MTX) influx and the Ki(leucovorin) for MTX uptake were lower in CCRF-CEM compared with LAZ-007 cells, the size of the difference does not seem adequate to explain differential protection. The extent of MTX polyglutamylation in CCRF-CEM and LAZ-007 cells was identical and the influence of leucovorin on MTX polyglutamylation was the same in both cell lines.

Cell Division↗
PubMed1985

Comparison of leucovorin protection from variety of antifolates in human lymphoid cell lines.

Leucovorin requirements for protection of the T cell line CCRF-CEM and the B cell line LAZ-007 against the cytotoxic effects of a variety of antifolates were studied. Differential leucovorin protection for DDMP-induced growth suppression occurred in the opposite direction to that for MTX, with CCRF-CEM requiring less leucovorin than LAZ-007 for equivalent protection. A pattern of differential protection from DDMP different from that of protection from MTX was also seen for the cell lines RAJI and MOLT-4. Differential leucovorin protection was observed for the chain-extended MTX analogue PT441. The degree of differential protection was similar to that seen for MTX, and transport studies showed that PT441 was a weak inhibitor of tritiated MTX uptake into CCRF-CEM cells. Differential leucovorin protection was observed for the lipophilic antifolate trimetrexate glucoronate (TMQ) but the degree of differential protection was smaller than that seen for PT441 or for MTX. Since TMQ is not transported into cells by the reduced folate system, while PT441 is a weak competitive inhibitor of [3H]MTX transport, and since neither is polyglutamylated, these results support the conclusion reached in previous experiments that differential leucovorin protection of MTX is unlikely to be a transport-related phenomenon and is not due to an effect on polyglutamylation. In addition, the different patterns of relative leucovorin requirements for DDMP and MTX protection suggest that differential metabolism or catabolism of leucovorin does not account for differential protection.

Biological Transport↗
PubMed1985

Changes in the characteristics of the bone marrow during therapy for acute non-lymphocytic leukemia: relationship to response to remission induction therapy.

The bone marrows of patients with acute non-lymphocytic leukemia being treated with 'high dose' cytosine arabinoside remission induction therapy were sampled prior to the initiation of chemotherapy, after 6 days of therapy and again 7 days after the conclusion of therapy. These studies demonstrated that the marrows of patients who would enter remission (CR patients) contained less leukemic cells prior to therapy than patients who would fail to enter remission because of persistent leukemia (resistant disease, or RD patients). A comparison of the day 6 and 7-day post-therapy marrows with the pretherapy marrow demonstrated that while the % reduction in leukemic cells was greater for CR patients than for RD patients, the absolute reduction in leukemic cell mass was the same for both groups. While there was no relationship between the percentage of cells in S phase and the pretherapy leukemic cell mass, the greater the pretherapy leukemic cell mass the greater the likelihood that the leukemic cells would be resistant to the metabolic effects of cytosine arabinoside in vitro.

Aged↗
PubMed1984

Inhibition of DNA synthesis by cytosine arabinoside: relation to response of acute non-lymphocytic leukemia to remission induction therapy and to stage of the disease.

The sensitivity of leukemic marrow cell DNA synthesis to cytosine arabinoside (araC) exposure in vitro was studied in specimens obtained from patients with acute non-lymphocytic leukemia. Cells from patients who had been treated with araC in the past were more likely to be resistant to the effect of araC on DNA synthesis than cells obtained from patients who had not been so-treated previously. Resistance to the effects of araC on DNA synthesis was associated with the failure of high-dose araC therapy to induce remissions in relapsed patients, whereas remission induction failure in previously untreated patients was not associated with araC resistance.

Acute Disease↗