Search PubMed⌕ Search

Biomedical subjects

D Bowen

Publications and source records attributed to D Bowen.

105 records · Page 6Linked to original sources
PubMedDate not supplied

Action steps to enhance minority opportunities.

There is much work to be done to enhance minority opportunities in healthcare administration. Through ACHE efforts and the commitment of individuals, healthcare executives can improve career opportunities for their minority colleagues.

Career Mobility↗
PubMedDate not supplied

Developing public policy competencies.

The importance of demonstrating competency in today's public policy environment cannot be overstated. In fact, the ability of a healthcare organization to make competitively sound strategic business decisions based on its public policy acumen may be key to its survival.

Hospital Administrators↗
PubMedDate not supplied

5-Fluorouracil simultaneously maintains methotrexate antineoplastic activity in human breast cancer and protects against methotrexate cytotoxicity in human bone marrow.

High-dose methotrexate (MTX) cytotoxicity is maintained in MCF-7 breast cancer cells but reduced in Hs824.T human bone marrow by a priming and nontoxic 5-fluorouracil (5-FU) dose. When MCF-7 breast or Hs824.T bone marrow cells are incubated with 10 microM 5-FU and 10 microM MTX for 48 h, the growth rates of breast cancer cells were 97.59 +/- 0.97% and 21.81 +/- 3.33% of the control rate, respectively, and the growth rates of bone marrow cells were 90.61 +/- 3.71% and 29.58 +/- 2.99% of the control rate. The combinations of 5-FU 2 h prior to MTX or MTX 2 h prior to 5-FU followed by a 48 h incubation, respectively, gave growth rates of 20.96 +/- 2.44% and 19.86 +/- 2.56% of the control rate for MCF-7 cells. In bone marrow cells, the combinations of 5-FU 2 h prior to MTX or MTX 2 h prior to 5-FU followed by a 48 h incubation, respectively, gave growth rates of 79.66 +/- 7.41% (protection) and 31.39 +/- 1.77% of the control rate. Similar patterns to bone marrow emerges in platelets. These studies suggest that: a) MTX and 5-FU combination on the growth of human MCF-7 breast cancer cells is independent of sequence; and b) a priming-dose of 5-FU will protect bone marrow from MTX cytotoxicity but not breast cancer cells. Therefore, a priming and non-toxic dose of 5-FU and MTX may have maximum antineoplastic activity while at the same time provide protection to the hematopoietic system.

Animals↗
PubMedDate not supplied

Selectivity in human breast cancer and human bone marrow using trimetrexate in combination with 5-fluorouracil.

The growth inhibitory effect of trimetrexate (TMQ) is maintained in MCF-7 breast cancer but is decreased in Hs 824.T human bone marrow cells by a priming- and non-toxic 5-fluorouracil (5-FU) dose. Incubation of MCF-7 breast cells with 10 microM TMQ alone or in combination with 10 M 5-FU (TMQ 2 h prior to 5-FU [TMQ/5-FU] or 5-FU 2 h prior to TMQ[5-FU/TMQ]) resulted in similar inhibitory effects but dissimilar effects occurred in Hs 824.T bone marrow. In breast cancer, the percentage differences among TMQ and TMQ/5-FU, TMQ and 5-FU/TMQ, and TMQ/5-FU and 5-FU/TMQ on growth rates, respectively, were 3.56%, 2.35%, and 1.68%. The percentage differences on growth rates of TMQ and TMQ/5-FU, TMQ and 5-FU/TMQ, and TMQ/5-FU and 5-FU/TMQ in bone marrow, respectively, were 5.76%, 30.03% (significant protection by 5-FU, i.e. the inhibitory effect of 5-FU/TMQ < or = TMQ), and 35.78% (sequence dependent). The growth rates of breast cancer and bone marrow cells in the presence of 5-FU were 96.03 +/- 1.17% and 94.59 +/- 1.15%, respectively, of control rates. These studies suggest that (a) TMQ and 5-FU combinations on the growth of MCF-7 breast cancer cells are independent of sequence of administration and best related to TMQ and (b) a priming- and non-toxic 5-FU dose protects against TMQ toxicity in human bone marrow while not affecting the maximum inhibitory effect of TMQ in breast cancer.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Sequence-dependent antagonism between tamoxifen and methotrexate in human breast cancer cells.

High-dose methotrexate (MTX) cytotoxicity is decreased in MCF-7 breast cancer cells when the chemoendocrine agent tamoxifen (TAM) is given to cells 24 hours prior to MTX (early TAM). However, when breast cancer cells are exposed to TAM 24 hours after MTX (delayed TAM), MTX cytotoxicity is enhanced by TAM. The growth of cells exposed to 10 microM TAM and 10 microM MTX alone or in combination with early TAM plus MTX had the following order: TAM > TAM (early) + MTX > MTX. The percentages of control rates for TAM, MTX, and TAM (early) + MTX are 74.71 +/- 1.36%, 22.13 +/- 2.76%, and 38.17 +/- 2.75%, respectively. The inhibitory sequence from cells exposed to MTX + TAM (delayed TAM), MTX and TAM alone is MTX + TAM (delayed TAM) > MTX > TAM; and the percentages of control rates were 16.87 87% (MTX + TAM [delayed TAM]), 25.92 +/- 2.14% (MTX), and 54.08 +/- 14.79% (TAM). These studies suggest that: (a) the interactions between TAM and MTX are sequence-dependent; (b) TAM antagonizes the effect of MTX when TAM administration precedes MTX; and (c) TAM enhances the effect of MTX when TAM administration follows MTX.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Toxicity, pathological effects, and antineoplastic activity of a non-toxic dose of 5-fluorouracil in combination with methotrexate.

The survival time of CF-1 mice bearing Ehrlich ascites tumor cells was increased significantly by i.p. administration of a non-toxic dose of 5-fluorouracil (25 mg/kg) followed by methotrexate (40 mg/kg). The effects of 5-fluorouracil (FU) and methotrexate (MTX), singly and in combination, were examined on the hematopoietic system (platelets, erythrocytes, leukocytes, and hematocrit), body weight, and the crypt of Liberkühn to assess toxicity, and on survival of tumor-bearing animals to assess antineoplastic activity. Sequential treatment with a non-toxic dose of FU followed by MTX for 3 consecutive days produced no significant adverse effect. MTX alone and the scheduling of FU after a priming dose of MTX resulted in: (a) a marked decrease in the hematopoietic parameters; (b) significant morphological changes in ileal tissue; and (c) a reduction in body weight. The survival of tumor-bearing animals treated with FU alone and FU 2 hours before MTX was 124% and 139% greater than control, respectively. The survival rate of animals treated with MTX alone was less than that of untreated tumor animals. This study suggests the feasibility of designing FU and MTX regimens that will have little or no systemic toxicity while maintaining antineoplastic activity.

Animals↗
PubMedDate not supplied

A preliminary pharmacokinetic evaluation of the antimetastatic immunomodulator swainsonine: clinical and toxic implications.

The pharmacokinetics of swainsonine (SW) was investigated in mice after intravenous administration of 3 micrograms/ml. The time course of SW blood levels followed a three-compartment open pharmacokinetic model which consisted of biphasic distribution, and a rapid elimination phase (terminal half-life, 31.6 min). After completion of the distribution, SW was widely distributed to the extravascular space (Vss, 22ml; Vd, 33ml). Free fractions of this substance were indistinguishable from unity, indicating little or no protein binding. The rate-limiting step in the elimination of SW from the body appears to be the slow return from the deep compartment into the central one. Accordingly, SW blood levels may be low and yet significant amounts of this agent may be present in different body organs and tissues. A comparison of SW tissue levels indicates that the highest amounts appeared in the bladder, kidney, and thymus, (3.8 0.5, and 2.2 nmoles/g wet wt) with the lowest levels consistently appearing in the brain (< 0.1 nmoles/g wet wt). Hence, this study suggest that: 1) SW has high affinity for the thymus, which is in part consistent with its previously published immunomodulatory action; 2) SW should be infused for at least 2 1/2 hrs for its concentration to approach a plateau (this is based on the short half-life of SW and its time to steady state); and 3) CNS toxicity may be dose-limiting and not be present at SW levels preventing metastasis.

Animals↗
PubMedDate not supplied

Importance of psychological variables in understanding risk perceptions and breast cancer screening of African American women.

African American women are less likely than white women to receive and perform adequate breast screening, and represent a group that has not been thoroughly researched in the area of breast cancer risk. In general, perceptions of risk and worry about cancer are both related to obtaining mammography and possibly other screening activities. We examine African American women's worry and beliefs about breast cancer, and their intentions to perform breast and genetic screening behaviors, using the self-regulatory model. Participants were recruited via media announcements; they completed questionnaires addressing several aspects of the self-regulatory model. Forty-one percent of participants were underestimators, 23% were overestimators, and 37% were extreme overestimators of their own personal risk for breast cancer. Several variables were significant predictors of willingness to undergo mammography and genetic screening, including ethnic identity, attitudes toward the physician, emotional distress, and risk overestimation. These data highlight the importance of psychological variables in understanding screening in African American women and hold promise for intervention design.

Adult↗
PubMedDate not supplied

Interaction of swainsonine with lymphoid and highly perfused tissues: a pharmacokinetics explanation for sustained immunomodulation.

The kinetics of inhibition of metastasis by the immunomodulator swainsonine (SW) is effective 1 to 3 days after administration. It is likely that SW's prolonged antimetastatic effect is due to its mitogenic property (spleenocytes isolated from animals treated with SW for 42-72 hours stimulated DNA synthesis that remained elevated for up to 3 days after removal of the drug from the drinking water). An analysis of SW in lymphoid (spleen and thymus) and highly perfused tissues was undertaken to determine if SW's sustained antimetastatic effect could be correlated to its retention. C57BL/6 mice received [3H]SW in drinking water for 24-72 hours and thereafter, received SW-free drinking for 24, 48, and 72 hours. Lymphoid and highly perfused tissues were analyzed for [3H]SW. At 24, 48, and 72 hours, spleen SW levels are, respectively, at least 2.33, 2.25, and 2.00 times greater than the perfused tissue; and thymus are, respectively, 1.44, 1.50, and 1.77 as great as the perfused tissue (kidney) with the highest SW level. These studies suggest that SW is predominantly retained for at least 72 hours, in lymphoid tissue. The targeting and retention of SW for lymphoid tissue days after removal of SW from animal drinking water is consistent with a) the immunomodulatory/mitogenic property and b) the sustained antimetastatic effect attributed to SW.

Adjuvants, Immunologic↗