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Biomedical subjects

B F Issell

Publications and source records attributed to B F Issell.

At least 19 recordsLinked to original sources

Participatory research in a Native Hawaiian community. The Wai'anae Cancer Research Project.

BACKGROUND: Community participation was a key component of a cancer control research project in a Native Hawaiian community. This project tested the effectiveness of a culturally appropriate intervention as a means of increasing breast and cervical cancer screening practices among Native Hawaiian women on the Wai'anae Coast of the island of O'ahu. METHODS: The Wai'anae Cancer Research project was community driven, with Native Hawaiian community representatives involved in all phases of the project, from grant proposal development to data interpretation. A community health center administered the grant award from the National Cancer Institute. The policymaking steering committee included community representatives, health professionals, and researchers to balance community and scientific quality standards. A factor in the project's success was continuous involvement over 7 years by a core of community representatives and professional staff. RESULTS: More than 500 women participated in the intervention, and outcome measures indicated that there was a community wide impact on cancer-related knowledge, attitudes, and behaviors. Important contributions of the project also included direct economic benefits, improvements in health services and systems, increased research capabilities, and dissemination of findings to other communities and researchers. CONCLUSION: Community participation in all phases of the research was essential in generating community acceptance and resulted in an innovative and effective intervention. This participatory research project has left the community richer in knowledge, skills, experience, confidence, and resources. These qualities provide a strong foundation for building future programs and research.

Breast Neoplasms

Barriers to mammography in a low income, multiethnic clinic population.

Breast cancer-related knowledge, attitudes, behaviors and barriers to obtaining a mammogram were assessed in women attending a primary care clinic serving a low-income minority population. Although most women believed in the value of mammograms, fewer than one in six was compliant with guidelines, and there were considerable deficits in knowledge about breast cancer risk. Ethnic and age differences in responses have implications for health program planning.

Adult

A breast and cervical cancer project in a native Hawaiian community: Wai'anae cancer research project.

BACKGROUND: This article describes a breast and cervical cancer control project in a Native Hawaiian community and presents preliminary findings from its first year. The project is community driven, with Native Hawaiian community investigators and advisors involved in all phases of the research project. Its purpose is to test the effectiveness of a culturally appropriate intervention as a means of increasing breast and cervical cancer screening practices among Native Hawaiian women. METHODS: This article discusses the process of community participation in the development of a baseline survey as well as selected findings from that survey. A baseline telephone survey was conducted to obtain an initial assessment of community knowledge, attitudes, and behavior related to cancer. Community representatives were an integral part of the research team that planned and implemented the survey. RESULTS: A total of 1,260 women drawn equally from the study and the control communities participated in the survey. A majority of those surveyed in both communities indicated adherence to cancer screening recommendations. Seventy-three percent of the women reported having obtained a Pap test during the past 2 years. Fifty-nine percent of women over 40 years of age reported having had a mammogram during the past 2 years. Twenty-eight percent reported having used Hawaiian remedies within the past year. Thirty-six percent of the women reported encouraging others to obtain cancer screening services. DISCUSSION: Though a majority of the target population are following cancer screening guidelines, a significant minority are not. While the project intervention aims to change the screening behavior of women not currently getting cancer screening, it plans to do so by enlisting the women already in compliance to reach others in their social networks who are currently not getting cancer screening. The involvement of community representatives, working alongside researchers, in baseline survey planning helped assure the survey was acceptable to the participants and the community as a whole. This process is illustrative of a participatory research commitment which underlies success in the early phase of this Native Hawaiian research project.

Adult

Prospects for immunotoxin therapy in cancer.

Immunotoxins are formed by chemically linking antibodies to "toxic" polypeptides that inactivate protein synthesis. These hybrid protein molecules are guided to tumor cells by the antibody moiety, and once bound to the tumor cells, the toxic polypeptide moiety penetrates the cell membrane and enzymatically inactivates protein synthesis. A stepwise approach to identifying the potential clinical uses of immunotoxins in cancer therapy is examined in this chapter.

Animals

Radioimmunoassay for etoposide and teniposide.

A radioimmunoassay for VP-16 or VM-26 was developed by using tritiated ligand and antisera produced from rabbits immunized with succinyl-VP-16 bovine serum albumin conjugates. Separate determinations of VP-16 and its hydroxy acid, a metabolite which cross-reacted with the VP-16 antisera, could be accomplished by extracting samples with chloroform in which the metabolite was insoluble. The assay was reproducible and sensitive. Extracted standard curves were linear from 0.025 to 5 micrograms for VP-16 and 0.1 to 10 micrograms for the hydroxy acid per 0.5 ml assay mixture. Fifty percent inhibition of binding was achieved at 0.066 and 0.55 microgram for VP-16 or VM-26 and the metabolite, respectively. Preliminary disposition studies in mice and dog, and human urinary excretion support the application of the assay in pharmacologic studies.

Animals

Clinical pharmacology of intraperitoneal cisplatin.

The clinical pharmacology of cisplatin was determined in six patients with malignant ascites secondary to ovarian cancer, and in one patient with peritoneal mesothelioma, following intraperitoneal administration of cisplatin (25-60 mg/m2). The drug was administered in 1 liter of normal saline as a 15- to 30-min infusion. Total, and in some patients free (ultrafilterable), platinum concentrations were determined in plasma, urine, and ascitic fluid by flameless atomic absorption spectrometry. The peak total platinum concentrations in ascitic fluid at the end of infusion were related to dose, a 50 mg/m2 dose producing a 20 to 80 micrograms cisplatin/ml concentration. Filterable platinum represented between 3 and 59% of total platinum in the peritoneum at 4 to 6.5 hr following its administration. Plasma platinum concentrations ranged between 0.2 to 1.6 micrograms/ml 4 hr following administration, and reached a plateau for the next 24 to 48 hr largely in the form of protein-bound platinum. The urinary excretion of cisplatin was consistent with variation in absorption from the peritoneum. Minimal gastrointestinal, bone marrow, and renal toxicities during therapy suggest that sustained free platinum concentrations in ascites may be obtained without significant toxicity and support the intraperitoneal route of administration as an effective strategy for cisplatin therapy of intra-abdominal malignancies.

Aged

Mitomycin: ten years after approval for marketing.

Mitomycin was approved for marketing by the Food and Drug Administration in 1974 for use in gastric and pancreatic carcinomas when combined with other chemotherapeutic agents. Since then, mitomycin has been used extensively in combination chemotherapy for a variety of tumors, particularly in the past seven years. However, the contribution of this agent to the various drug regimens has not been adequately defined. Clear evidence of the drug's activity as a single agent has been seen in the intravesical treatment of superficial bladder carcinoma. Common toxicities include anorexia, vomiting, and myelosuppression. Less common, but potentially lethal, toxicities in the form of fibrosing alveolitis and microangiopathic hemolytic anemia with renal failure are being reported with increasing frequency. These potentially severe adverse effects, coupled with the still undefined role of mitomycin in systemic cancer chemotherapy, suggest that selection of this drug for other than investigational use should be made with care.

Antineoplastic Agents

Cell-mediated inhibition of tumor colony formation in agarose by resting and interleukin 2-stimulated human lymphocytes.

Human nonadherent peripheral blood mononuclear cells (PBMC) isolated from nonimmunized donors were preincubated for 18 h in medium alone or medium containing the lymphokine interleukin 2 and subsequently cocultured with tumor cells derived from malignant tumor cell lines or from fresh human tumors. The cell suspensions were subsequently inoculated into agarose; 14 days later, new tumor colony formation was determined. Although the different tumor cells displayed a wide range of sensitivity to the PBMC, in each instance, the number of colonies formed by the tumor cells exposed to the PBMC was consistently reduced relative to that of control cells. The inhibitory effect on the colony-forming cells was especially pronounced with PBMC preincubated with interleukin-2 and was dependent on the ratio of tumor cells to PBMC in the culture. This assay system provides an alternative to the standard 51Cr release assays in assessing the immunomodulatory effects of lymphokines and in quantitating the cytolytic or cytostatic activity of various effector cells against neoplastic stem cells from established cell lines and from heterogeneous cell preparations derived from fresh human tumors.

Cell Line

Mitomycin C intravesical therapy in noninvasive bladder cancer after failure on thiotepa.

Mitomycin C 40 mg in 40 ml water was administered intravesically every week for 8 consecutive weeks to 60 patients with superficial bladder cancer. All patients had failed treatment with intravesical thiotepa and had evaluable disease. An objective response of 50% or greater reduction in measured tumor mucosal involvement was obtained in 68% of patients. Forty-two percent of the patients achieved a complete response, and this included 50% of patients with Grade III disease and 70% of patients with a T1 tumor. Median response duration in complete responders was 12.2 months with a range of 3.5 to 24.3 + months. Fifty-five percent of patients are still responding. Therapy was generally well tolerated, and in contrast to thiotepa, myelosuppression was not the dose-limiting effect. One third of all patients experienced symptoms of local irritation, and skin reactions were seen in 12% of patients.

Adult

The human tumor colony-forming chemosensitivity assay: a biological and clinical review.

Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity assay (CFCA). The true positive rate in over 1600 correlations is 71% and the true negative rate is 94%. The biological elements of the assay, its developmental history, its place in the spectrum of in vitro chemosensitivity assays, and its theoretical and practical limitations are discussed. The scope, design, and limitations of key clinical trials are presented and an analysis of the potential errors of statistical interpretation of the trials as well as the results of the trials is given.

Antineoplastic Agents

Disposition of orally administered 14C-prednimustine in cancer patients.

A single oral solution dose (40 mg/m2) of 14C-prednimustine was administered to each of four cancer patients. Plasma, urine, and feces were collected at appropriate times and analyzed for total radioactivity. Plasma samples were analyzed for prednimustine. Peak plasma levels of radioactivity (1-3 micrograms 14C-prednimustine equivalents) occurred at 1.5-3 h in three patients and at 5-6 h in one patient. No intact prednimustine was detected in the plasma; this means that if present, it would be at a concentration of 0.02 micrograms/ml or less and would account for less than 1% of the total drug-related material at the time of peak plasma levels. Solvent-extractable metabolites had a plasma half-life of about 8 h or less. By 24 h essentially all the plasma radioactivity appeared to be covalently bound, and it was eliminated slowly with an estimated terminal elimination half-life of about 10 days. Rapid urinary excretion occurred in the first 24 h, and 40%-60% of the dose was recovered in the urine in 72 h. Although prednimustine was well absorbed, the ester was subject to extensive presystemic metabolism and was not present in the systemic circulation after oral administration.

Adenocarcinoma

The podophyllotoxin derivatives VP16-213 and VM26.

VP16-213 and VM26 are compounds with definite anticancer activity in specific tumor types. Despite 10 years of clinical development the full impact of these compounds in current cancer therapy requires further study. There is no conclusive evidence that one compound is superior to the other in any specific tumor type. The composite activities suggest possible differences in certain cancers such as small cell anaplastic lung cancer, lymphoma, leukemia, bladder and ovarian cancer, but sufficiently adequate studies to determine this have not been reported for any tumor. Understanding the basic pharmacology of these compounds should also be considered of high priority since it is obvious that there is much to learn in this area and further clarification should allow improved clinical utilization. It is hoped that the presentations and discussions of the First International Symposium will generate a new wave of interest in future podophyllotoxin research and development.

Animals

Etoposide (VP16-213) and teniposide (VM26) comparative in vitro activities in human tumors.

In order to determine if any inherent sensitivity differences may exist between VP16-213 and VM26 individual human tumors were grown in vitro and drug sensitivities were determined using the soft agar clonogenic assay method. Only nine of the 34 tumors tested so far showed a differing sensitivity to VP16-213 and VM26 as measured by a 25% or greater colony number reduction. However in none of these tumors did this added reduction result in a 70% decrease over control plate colony numbers. As yet we have been unable to demonstrate any clinically meaningful inherent in vitro sensitivity difference between VP16-213 and VM26 in any tumor type tested.

Antineoplastic Agents