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Biomedical subjects

T Maloney

Publications and source records attributed to T Maloney.

28 records · Page 2Linked to original sources

Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study.

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP to two years of intermittent L-PAM in women with operable breast cancer with histologically positive axillary lymph nodes. In fully evaluable patients with a 42-month median and 30-month minimum follow-up, treatment failures have occurred in 26% of 145 receiving CMFVP and 47% of 167 women given L-PAM (P = 0.002). Disease-free survival times were significantly longer with CMFVP than with L-PAM in the following subgroups: premenopausal women (P = 0.002), postmenopausal women (P = 0.002), women with 1-3 involved axillary nodes (P = 0.003), and women with four or more involved axillary nodes (P = 0.002). CMFVP was effective in pre- and postmenopausal women. There is a significant difference in survival in favor of CMFVP compared to L-PAM (P = 0.005). The life table estimates of survival at 42 months are 86% for women on the CMFVP treatment arm and 73% for women on the L-PAM treatment arm. There was no correlation between the interval from mastectomy to onset of chemotherapy (between one and six weeks) and recurrence rates. Acute toxicity with both treatment arms was moderate and reversible. These results show that continuous CMFVP is superior to intermittent L-PAM in decreasing recurrences and increasing survival in both pre- and postmenopausal women with operable breast cancer with histologically involved axillary nodes.

Breast Neoplasms↗

Tamoxifen and oophorectomy in the treatment of recurrent breast cancer: a Southwest Oncology Group Study.

The relatively short survival following chemotherapy in patients with metastatic carcinoma of the breast and the introduction of antiestrogens has led to renewed interest in the hormonal therapy of breast cancer. Pritchard et al. (Cancer Treat. Rep., 64: 787-796, 1980) have recently stated that response to the antiestrogen tamoxifen (TAM) strongly predicts a subsequent response to oophorectomy in premenopausal patients. The Southwest Oncology Group administered TAM to pre- and postmenopausal women with first recurrence of breast cancer. Following response and subsequent relapse, or after no response, patients underwent an oophorectomy while continuing on TAM. None of 14 premenopausal patients who responded to TAM had a response to oophorectomy plus TAM, while 5 of 22 had a remission with oophorectomy plus TAM after initially failing with TAM alone. The reverse was seen in postmenopausal women; 4 of 18 responders to TAM subsequently responded to oophorectomy plus TAM, but none of 18 TAM failures responded to oophorectomy plus TAM. These results suggest that in the premenopausal women the TAM dose may be insufficient to block all estrogen action and that oophorectomy, by removing the major source of estrogen, can result in a more effective antiestrogen action of TAM leading to a response. No explanation is readily available for the results in postmenopausal patients.

Breast Neoplasms↗

Stability of diluted heparin sodium stored in plastic syringes.

The stability of heparin diluted in 0.9% sodium chloride injection and stored in plastic syringes for a three-week period was studied. Heparin activity was assayed by the activated partial thromboplastin time (APTT) method. Heparin sodium (25,000 units/ml) was diluted to 500 units/ml and stored in 50-ml polypropylene syringes. Concentrations were compared in two brands of syringes stored at room temperature in the dark. In another experiment controlled for order-related assay errors, heparin was stored in one brand by syringe at either 0-4 degrees C or room temperature. There was a statistically decrease in heparin activity over three weeks in both syringes and at both 0-4 degrees C and room temperature. However, the overall drop in activity was only about 8%. Analysis of covariance confirmed significant regression with time at both temperatures. An unexpected finding was that heparin at 500 units/ml consistently assayed higher than this value. A study of the effect of glass and plastic showed that when heparin was diluted into either a glass or plastic container, there was significantly less heparin activity in the glass containers within two hours. One possible explantation for this phenomenon is absorption of heparin to glass surfaces. It was concluded that heparin can be stored in polypropylene syringe for up to three weeks without refrigeration. However, once diluted, heparin should not be stored in glass containers.

Drug Packaging↗

Phenotypic variance among cells isolated from spontaneous mouse mammary tumors in primary suspension culture.

A method is given for selecting epithelial cells directly from primary mammary tumors in Methocel suspension culture. The frequency of colony-forming units in primary tumors was approximately 10(-4). Colonies grew by cell division; formation and growth of colonies was cell density dependent. Five Methocel isolates were established in monolayer culture and characterized. Two were epithelial, evidenced by functional occluding junctions. The other three were not typed in vitro, although they formed carcinomas in vivo. All were subtetraploid by passage 10. There were variations in ability of the five Methocel isolates to reclone in suspension that appeared to be due to the evolution of anchorage-dependent variants during their growth in monolayer culture. These variants could be purified by limiting dilution plating on solid substrates. The five Methocel isolates and their derivative variants were used to determine correlations between transformation markers and tumorigenicity. Only three Methocel-derived sublines of nine tested, including two recloned in Methocel, were tumorigenic at all when inoculated in two sites of three syngeneic hosts, one athymic. The other six were nontumorigenic. The tumorigenic sublines were less tumorigenic than uncultured cells of parent tumors or parent tumor cells grown in primary monolayer culture. Thus, anchorage-independent growth is not a reliable marker for the tumorigenic mammary phenotype. No correlation was found between two other "contact-related" transformation markers, rapid growth rate and monolayer overgrowth, and tumorigenicity. The three transformation markers were expressed independently. Both tumorigenic and nontumorigenic sublines expressed mammary tumor virus antigens M.W. 28,000 protein and M.W. 52,000 glycoprotein, although only a minor fraction of cells contained the M.W. 52,000 glycoprotein. These data emphasize the heterogeneity of phenotypes in mammary tumors as well as differences between fibroblasts and mammary epithelium in models of neoplastic transformation.

Animals↗

Effects of hypnotics on the sleep EEG of healthy young adults: new data and psychopharmacologic implications.

Benzodiazepine hypnotics increase NREM sleep and alter its EEG by reducing delta (0.3-3 Hz) and increasing sigma (12-15 Hz) and beta (15-23 Hz) activity. We tested whether the nonbenzodiazepine hypnotic, zolpidem (10 mg), produced the same pattern of sleep and EEG changes as two "classical" benzodiazepines, triazolam (0.25 mg) and temazepam (30 mg). Sleep EEG of 16 subjects was analyzed with period amplitude analysis for 3 nights during drug administration or placebo. The effects of zolpidem were in the same direction but generally of smaller magnitude than those of the classical benzodiazepines. These differences are more likely the result of non-equivalent dosages than different pharmacologic actions. Period amplitude analysis showed that the decreased delta activity resulted mainly from a decrease in wave amplitude. In contrast, the increased sigma and beta activity were produced by increased wave incidence. Delta suppression increased with repeated drug administration but sigma and beta stimulation did not. While these findings have little relevance for the clinical choice of hypnotics they may hold important implications for the brain mechanisms involved in hypnotic tolerance and withdrawal delirium.

Adult↗

Vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II) in disseminated testicular cancer: preliminary report of a Southwest Oncology Group Study.

Combination induction chemotherapy consisting of vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II) was administered to 126 patients with advanced germ cell tumors of the testis. Following this 4-month induction therapy, maintenance treatment consisting of chlorambucil and actinomycin D alternating monthly with vinblastine was given for an additional 20-month period. Sixty-four patients (51%) achieved a complete remission, while 33 patients (26%) achieved a partial response. Responses were observed in all histologic categories. Seven patients (11%), who were in complete remission, have relapsed at a median time of 5 months. Median duration of remission is greater than 12 months for complete responders and 4 months for partial responders. Significant leukopenia was noted in 57% of evaluable courses and significant thrombocytopenia was noted in 18%. Less than 20% of patients were noted to have nephrotoxicity. Other toxic effects observed were gastrointestinal (42%), dermatologic (15%), pyrexia (14%), neuromuscular (9%), and pulmonary (less than 5%). Several pretreatment parameters are currently being evaluated to determine the impact on complete remission rate and survival.

Antineoplastic Agents↗