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Biomedical subjects

M Collier

Publications and source records attributed to M Collier.

At least 19 recordsLinked to original sources
PubMed1991

Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies.

A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.

Administration, Oral↗
PubMed1991

Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.

Administration, Oral↗
PubMed1990

Measurement of human embryo-derived platelet-activating factor (PAF) using a quantitative bioassay of platelet aggregation.

A quantitative bioassay was used to measure the concentration of platelet activating factor (PAF) in medium in which human embryos produced by IVF had been cultured and in various other biological fluids. Following extraction and partial purification, 121 of 228 (53%) media samples in which single human embryos were cultured for 24 h had PAF levels greater than found in corresponding control media. This was assigned as embryo-derived PAF and the corresponding embryos termed 'PAF-positive'. Medium from those PAF-positive embryos transferred to patients who achieved an ongoing pregnancy had a mean PAF concentration of 295 +/- 107 nM (mean +/- SEM, n = 55), which was significantly greater (P less than 0.03) than media of PAF-positive embryos transferred to patients who failed to become pregnant (75 +/- 27 nM, n = 66, t-test). The embryos with the faster cleavage rates tended to secrete more PAF (P less than 0.01). Although a greater proportion of culture media derived from embryos transferred to patients who achieved a pregnancy were PAF-positive (66 out of 121, 54.5%) compared with those transferred to patients who failed to achieve a pregnancy (55 out of 121, 45.4%), this was not significant (P greater than 0.05). It was observed that 13% of women who achieved a pregnancy had embryos transferred which did not produce significant amounts of PAF in vitro. This occurred in 26% of women not achieving pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Assay↗
PubMed1990

Comparison of false-positive reactions in direct-binding anti-HIV ELISA using cell lysate or recombinant antigens.

In a 2-year study of false-positive anti-HIV-1 tests in blood donors at Manchester and Lancaster Blood Banks, the reactions associated with a HIV-infected cell lysate antigen were compared with those using recombinant-antigen-based tests. In year 1 (cell lysate test) at Manchester BTS 0.21% of 119.178 donations were repeatedly reactive, compared with 0.53% of 119,004 donations in year 2 (recombinant antigen). Reactive sera were tested at Manchester PHL by three different immunoassays. Referred specimens were classified as anti-HIV positive (95-100% reactive in all the assays), equivocal or negative (negative results in all three immunoassays). Two donors were confirmed to be anti-HIV positive over the 2-year period. Most sera were negative by confirmatory immunoassays in years 1 and 2. In year 1, a study of 60 referred sera with sex- and age-matched controls showed high correlation between a reactive anti-HIV-1 screening test and indeterminate anti-HIV-1 patterns on Western blot showing reactions with HIV gag-coded proteins. In year 2, less than 10% of referred sera were reactive by Western blot, and there was no correlation between a reactive screening anti-HIV test, the strength of signal in the test or a reactive Western blot. Follow-up showed that donors whose sera were reactive in years 1 and 2 by the anti-HIV-1 screening test formed almost two different populations. Four donors with equivocal anti-HIV-1 confirmatory tests had anti-HIV 'envelope' reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗
PubMed1990

A sore point.

Explore the source record for details and available documents.

Humans↗
PubMed1989

Supplementation of in-vitro fertilisation culture medium with platelet activating factor.

The supplementation of culture medium with platelet activating factor (PAF) on the subsequent implantation and pregnancy potential of pre-embryos produced by in-vitro fertilisation was studied. Pre-embryo culture medium was supplemented with 0 (control), 0.186, 0.93, or 1.49 mumol/1 PAF. Pre-embryos were transferred to PAF-containing medium 15-17 h after insemination (ie, just before syngamy) for 24 h and then transferred to the uterus. For 185 women receiving control pre-embryos, the pregnancy rate (positive beta human chorionic gonadotropin per oocyte retrieval) was 10.2%, while 166 women who received PAF treated pre-embryos (all concentrations combined) achieved a pregnancy rate of 17.5%. This difference was significant. The pregnancy rates per pre-embryo transferred were 6.1% and 9.4% for the control and PAF groups, respectively. The percentage of positive pregnancy tests that resulted in a viable pregnancy (presence of fetal heart at 8 weeks) was 78.9% in the controls and 75.9% in the PAF group. There was no difference in the average number of embryos transferred in either group. The increase in the pregnancy rate after a short exposure of pre-embryos to PAF in vitro suggests that PAF mediates pre-embryo development.

Chorionic Gonadotropin↗
PubMed1989

Clinical experience with leucovorin and 5-fluorouracil.

Two trials of leucovorin (LV) and 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer were done, both using a 3-day loading dose and then weekly doses to minimize toxicity. The first trial used LV administered by intravenous infusion with a constant dose of 5-FU 400 mg/m2, and the second trail used oral LV with increasing doses of 5-FU. In the first trail, 45 eligible patients (20 with and 25 without previous therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing the 5-FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients; these correlated with prolonged survival. Median survival was 8 months for patients with previous treatment and 10 for those without. Twelve-month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was conducted recently in cooperation with Duke University to determine toxicity and efficacy of oral LV with intravenous 5-FU before a randomized trial of this combination versus placebo with intravenous 5-FU. Eighteen patients were treated, and serum levels of folates were obtained on ten. First toxicity occurred at 5-FU doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in nine, lethargy in seven, nausea/vomiting in four, dermatitis in four, conjunctivitis in two, hypersalivation in two, stomatitis in one, and profound granulocytopenia in one. Response rate was 35%, and stabilization was 35% with median survival of 14 months. Twelve-month survival was 56%.

Adenocarcinoma↗
PubMed1988

Clinical experience with CF-FUra.

Two trials of CF-FUra in patients with metastatic colorectal cancer were performed, both using a 3 day loading dose and then weekly maintenance doses to minimize toxicity. The first trial used CF by IV infusion with constant dose of FUra 400 mg/m2, and the second trial used oral CF with escalating doses of FUra. In the first trial, 45 eligible patients (20 with and 25 without prior therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing 5FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients, and correlated with prolonged survival. Median survival was 8 months for patients with prior treatment and 10 for those without, and 12 month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was recently conducted in cooperation with Duke University to determine toxicity and efficacy of oral CP with IV FUra prior to a randomized trial of this combination versus placebo with IV FUra. Eighteen patients were treated and serum levels of folates were obtained on 10. First toxicity occurred at FUra doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in 9, lethargy in 7, nausea/vomiting in 4, dermatitis in 4, conjunctivitis in 2, hypersalivation in 2, stomatitis in 1, and profound granulocytopenia in 1. Response rate was 35% and stabilization was 35% with median survival of 14 months and 12 month survival of 56%.

Adenocarcinoma↗
PubMed1988

Biochemical and pharmacological characterization of human embryo-derived platelet activating factor.

The soluble platelet activating factor (PAF) produced by mouse embryos was shown to have properties similar to 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (PAF-acether). In this study PAF was extracted from the medium in which human embryos were cultured for approximately 18 h prior to transfer. The extracted embryo-derived PAF moved on silica thin layer chromatograms with the same RF of 0.26 +/- 0.03 (n = 26) as PAF-acether. Embryo-derived PAF or PAF-acether activity was assayed by monitoring the decrease in the proportion of single platelets in rabbit whole blood due to aggregation on incubation at 37 degrees C. The two agonists were said to be of the same activity, if they induced the same degree of platelet aggregation after 15 min incubation. PAF-acether (93 nM) and embryo-derived PAF of similar activity induced an identical time response of platelet aggregation, the response being maximal by 6 min. PAF-acether, over the range 5.6-200 nM, induced a decrease that was linear when plotted on a log-log scale. Embryo-derived PAF and PAF-acether (184 nM) gave identical dose responses when serially diluted to 16 nM. Pharmacologically, the action of embryo-derived PAF and PAF-acether (46 nM) on platelet aggregation was significantly inhibited by 3.75 microM of the PAF-specific receptor inhibitor, SRI 63-441, and completely inhibited at 15 microM SRI 63-441. Embryo-derived PAF and PAF-acether (184 nM) were inactivated to the same degree by incubation with 5-13 IU/ml phospholipase A2 (pA2).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗