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Biomedical subjects

R R Love

Publications and source records attributed to R R Love.

At least 55 records · Page 3Linked to original sources
PubMed1993

Frequency and determinants of screening for breast cancer in primary care group practice.

BACKGROUND: Many studies reporting the frequency of breast cancer screening have been based only on physician and patient surveys or on data from quality assurance studies and do not assess the reliability of information obtained from these various sources. METHODS: To obtain more complete data we studied mammography performed in a 3-year period, 1988 through 1991, in 24 nonacademic primary care group practices by both auditing the medical records and obtaining questionnaire responses from 1819 women aged 53 to 62 years and from their 98 physicians in the nonmetropolitan Midwest. RESULTS: Medical record data indicated that mammography was performed in all 3 years in 16.7%, in at least two of 3 years in 49.8%, and in at least one of 3 years in 81.7% of women. While patient reports of a family history of breast cancer, health insurance coverage for mammography, and greater annual household income were each significant predictors, a patient report that a clinic staff member had discussed mammography was the strongest predictor of greater frequency of mammography. CONCLUSIONS: In this study of self-selected physicians and their patients, record-documented mammographic examinations were considerably more frequent than has been reported in some studies, but occurred at rates consistent with quality assurance data for the region. These data suggest that clinic staff initiatives with screening mammography have a large impact.

Breast Neoplasms↗
PubMed1993

Randomized phase I chemoprevention dose-seeking study of alpha-difluoromethylornithine.

BACKGROUND: alpha-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. Levels of ODC are closely related to tumor promotion, and inhibition of ODC is associated with suppression of tumor development in laboratory animals. DFMO has shown a dose-response effect in tumor inhibition in mice. PURPOSE: A randomized phase I study of DFMO was conducted to determine the lowest daily oral dose that can achieve at least 50% inhibition of ODC activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human skin, with minimal clinical toxicity (grade 1 or lower; Eastern Cooperative Oncology Group [ECOG]). METHODS: Cancer patients entered in steps 1 and 2 of the study had been treated and had no clinical evidence of cancer. In step 1, 13 patients received 0.125, 0.25, 0.5, or 0.75 g/m2 DFMO four times a day. In step 2, 13 patients received 0.125 or 0.25 g/m2 four times a day or 0.5 or 1.0 g/m2 every day. The 26 patients treated in steps 1 and 2 (range, < 1-6 months) had colon, prostate, or bladder cancer. In step 3, six cancer-free subjects at risk for colorectal cancer received 0.5 g/m2 every day for 5-12 months. To evaluate the effectiveness of DFMO in reducing TPA-induced ODC activity, we calculated the percent change from pretreatment ODC levels in skin biopsy specimens and the percentage of subjects with at least a 50% reduction in ODC levels. RESULTS: In step 1 of the study, treatment-limiting audiotoxicity was observed at the three highest doses. Because the only dose with no major toxic effects in step 2 was 0.5 g/m2 every day, that dose was administered in step 3, with no major toxic effects. Seven subjects treated with 0.5 g/m2 every day had pretreatment ODC levels in the normal range; five averaged a reduction in ODC activity of at least 50%. DFMO had linear pharmacokinetics over the entire dose range. When 0.5 g/m2 was given every day, the peak plasma concentration was 47.1 +/- 5.1 microM at 3-4 hours (monthly mean +/- SE, 14.5 +/- 5.2 microM); half-life was 3.5 hours; and area under the curve for plasma concentration x time for a single dose of DFMO was 311 +/- 39 microM x hour. CONCLUSIONS: These data support phase II chemoprevention studies with DFMO given at a dose of 0.5 g/m2 every day. IMPLICATIONS: Studies investigating prevention of cancers with DFMO are under consideration.

Adult↗
PubMed1993

A comparison of knowledge and communication skill evaluations by written essay and oral examinations in preclinical medical students.

While both oral and written communication skills are important in the daily work of physicians, medical school evaluation methods focus on content of written essays or often answers to multiple choice questions. To determine the feasibility and value of oral examinations for preclinical medical students, we gave a written short essay examination and an oral examination on the same question to 106 second-year medical students in a required neoplastic diseases course. Examination performance by each method was evaluated according to the same specific content and, separately, based on four communication skills criteria. We found high levels of inter-rater reliability with two oral examiners for both content and skills. Content and skills performance on both written and oral evaluations could be separately determined. Content performance was greater on the written evaluation.

Achievement↗
PubMed1993

Metastatic breast cancer 39 years after primary treatment.

The appearance of metastatic disease decades after primary treatment for cancers occurs rarely with cancers of the breast, malignant melanoma, and cancers of the kidney. Certainty about the relationship of primary and metastatic cancers is often limited by the absence of tissues showing identical histology, omission of various procedures and tests ruling out a new primary cancer, and follow-up data with treatment which supports the case for late recurrence. We report here the unusual case of an 84-year-old woman initially treated with mastectomies for a benign breast condition at age 39 and invasive breast adenocarcinoma at age 44. A pleural effusion developed at age 83 which showed adenocarcinoma. Physical examination and an extensive evaluation were unrevealing. Hormonal treatment has sustained remission of disease for 1 year.

Adenocarcinoma↗
PubMed1993

Tamoxifen therapy in breast cancer control worldwide.

In most developed and many developing countries, breast cancer is the most frequent cancer and the leading cause of cancer death among women. At least 50% of all breast cancer patients worldwide would survive longer, however, if public awareness about and early detection of the condition were increased and greater use were made of efficient treatment of proven value. With early-stage, localized breast cancer, local treatment combined with adjuvant hormonal therapy with tamoxifen, a synthetic estrogen, could save the lives of 6 women out of 100 compared with local treatment alone. Tamoxifen has anti-estrogenic effects not only on breast cancer cells but also on liver metabolism and bone, with concomitant decreases in risk factors for chronic skeletal and vascular system diseases. Long-term tamoxifen treatment causes major adverse clinical effects in < 5% of women; menopausal and vasomotor symptoms occur in the majority of treated women, but their severity lessens over time. Tamoxifen is being considered as a standard therapy and is included in the WHO list of essential drugs for the treatment of breast cancer patients in both developing and developed countries. For the control of breast cancer more successfully worldwide, one challenge is to make tamoxifen therapy available to greater numbers of women.

Adult↗
PubMed1992

Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer.

BACKGROUND AND METHODS: Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node-negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. RESULTS: In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P less than 0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteocalcin and alkaline phosphatase concentrations decreased significantly in women given tamoxifen (P less than 0.001 for each variable), whereas serum parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not change significantly in either group. CONCLUSIONS: In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine. Whether this favorable effect on bone mineral density is accompanied by a decrease in the risk of fractures remains to be determined.

Alkaline Phosphatase↗
PubMed1992

Tamoxifen in axillary node--negative breast cancer: multisystem benefits and risks.

Adjuvant tamoxifen therapy is associated with modest improvement in disease-free and overall survival in women with invasive axillary node-negative breast cancer. The preponderance of data supporting these general conclusions are from trials in postmenopausal women; in premenopausal women data appear convincing regarding disease-free, but not overall, survival. Firm conclusions regarding magnitude of benefit related to presence of different prognostic factors cannot be drawn at present. In postmenopausal women tamoxifen appears to alter favorably some risk factors for cardiovascular diseases and osteoporosis, which are the most common causes of mortality or morbidity in older American women. Adjuvant tamoxifen is associated with a significantly reduced risk of second primary breast cancer. Major serious risks of tamoxifen therapy include depression, and possibly thrombophlebitis and uterine endometrial cancer. Symptomatic vasomotor and gynecological side effects are frequent. Decision making with women should include assessment of these multisystem benefits and risks.

Breast Neoplasms↗
PubMed1992

Tamoxifen prophylaxis in breast cancer.

An increasing body of data suggests that tamoxifen can suppress development of preclinical breast cancer. Newer data in postmenopausal women also demonstrate major biologic effects of tamoxifen on risk factors for cardiovascular disease and osteoporosis. Taken together, this information supports the hypotheses that use of tamoxifen will provide overall health benefits and lower the incidence of breast cancer in selected women, particularly postmenopausal women, who are willing to take a daily hormone pill indefinitely and who do not develop significant symptomatic side effects. Clinical trials addressing these hypotheses are beginning in the United States, Great Britain, and Italy, but the design and completion of such trials present significant challenges. Until clear data are available from the clinical trials just being launched, tamoxifen should not be given to healthy women who do not have breast cancer.

Breast Neoplasms↗
PubMed1992

Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy.

Adjuvant therapy for breast cancer with tamoxifen is suggested to be of benefit to both women with negative and women with positive axillary nodes, and treatment lasting several years is currently being investigated. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible mechanisms of this effect, we evaluated changes in antithrombin III levels, fibrinogen levels, and platelet counts in 140 postmenopausal women with surgically resected breast cancer who were disease free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. Antithrombin III levels, elevated at baseline evaluation, decreased in tamoxifen-treated subjects at 6 months, but no subject exhibited a drop to clinically significant levels. Fibrinogen levels decreased 15% (0.4 g/L) in tamoxifen-treated subjects at 6 months. Platelet counts decreased 7% to 9% from baseline to evaluations at 3, 6, 12, 18, and 24 months in tamoxifen-treated subjects. While these changes do not explain the possible small thrombophlebitis-promoting effect of tamoxifen, the decrease in fibrinogen levels might be expected to be associated with a decreased risk of arterial thrombosis.

Antithrombin III↗
PubMed1991

Effects of tamoxifen on cardiovascular risk factors in postmenopausal women.

OBJECTIVE: To determine the effects of tamoxifen on risk factors for cardiovascular disease in disease-free postmenopausal women. DESIGN: Double-blind, placebo-controlled, randomized 2-year clinical trial. SETTING: University health sciences center. PATIENTS: Clinically postmenopausal women (140) with a diagnosis of axillary node-negative breast cancer, who were disease-free by laboratory and clinical evaluations. MEASUREMENTS: Levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, glucose, weight, blood pressure, and reported exercise and work activity were measured. MAIN RESULTS: Postmenopausal women receiving tamoxifen were evaluated at 3- or 6-month intervals during a 2-year assessment period and showed a mean decrease of 12% in total cholesterol levels (at 24 months -0.672 mmol/L; 95% CI, -0.839 to -0.505 mmol/L) and a mean decrease of 20% in calculated low-density lipoprotein (LDL) cholesterol levels (at 24 months, -0.725 mmol/L; 95% CI, -0.868 to -0.583 mmol/L) (P less than 0.001). Women with greater baseline cholesterol levels had greater decreases with tamoxifen treatment. Levels of HDL cholesterol decreased in patients treated with tamoxifen, but this decrease was only statistically significant at one of five measurement times. Apolipoprotein A-I levels increased significantly at the two time points at which it was measured (P = 0.02), and apolipoprotein B levels decreased significantly at these times (P less than 0.01) in patients treated with tamoxifen. Plasma glucose levels, reported exercise and work activity, reported smoking, weight, and systolic and diastolic blood pressures did not change with treatment. CONCLUSION: During 2 years of treatment, tamoxifen showed generally favorable effects on the lipid and lipoprotein profile of treated postmenopausal women. These effects may partially explain the decrease in adverse events and in mortality related to coronary heart disease seen in patients receiving adjuvant tamoxifen treatment.

Apolipoprotein A-I↗
PubMed1991

Prolactin and growth hormone levels in premenopausal women with breast cancer and healthy women with a strong family history of breast cancer.

Although both prolactin and growth hormone are believed to play roles in the development and growth of rodent mammary cancer, the role of these hormones in human breast cancer is uncertain. Under carefully specified conditions, serum levels of these hormones were determined by radioimmunoassay (RIA) and prolactin was determined by bioassay in 18 premenopausal women with breast cancer, 23 healthy women with a strong family history of breast cancer, and 39 healthy women with no significant family history of breast cancer. Parity was associated strongly with decreased prolactin levels, and increasing age was associated strongly with decreased growth hormone levels. After controlling for these variables, no differences in prolactin or growth hormone levels were found among the three groups of women. These data do not support roles for these RIA-measured hormones or bioassay-measured prolactin in premenopausal or familial breast cancer in omnivorous white women.

Adult↗
PubMed1991

Antiestrogen chemoprevention of breast cancer: critical issues and research.

Estrogenic hormones play critical roles in many aspects of women's health. Therefore, the impact of any hormonal manipulation must be carefully considered. While the evidence is good that chemoprevention, or more accurately chemosuppression, of breast cancer with tamoxifen is possible, further data are needed to support the case that hormone replacement with tamoxifen in healthy postmenopausal women would provide overall health benefits. Specifically, further data are needed regarding the biological effects of tamoxifen on risk factors for cardiovascular disease, on bone, on the liver, on the uterus, and on the coagulation system. Frequency, severity, and predictors for vasomotor, gynecologic, and depressant side effects also need to be well described. These data will allow rigorous cost-effectiveness analysis of hormone replacement therapies with tamoxifen and estrogen, as well as an analysis of the cost effectiveness of a clinical trial to prove definitively critical health benefits.

Breast Neoplasms↗
PubMed1991

The behavioral dynamics of clinical trials.

Two ways of approaching the design of long-term clinical trials are presented and contrasted. The first, termed the "static" view, emphasizes close adherence to formal rules of study design. The second, termed the "dynamic" view, emphasizes the behavioral aspects of patient participation in trials of long duration. The dynamic view is discussed in detail, with discussion of how recruitment of participants, random assignment to conditions, compliance with protocol, and measurement of outcomes are affected by behavioral dynamics. Data from a recently completed tamoxifen toxicity trial are used to illustrate the points and to focus the discussion of behavioral dynamics on the design of a chemoprevention trial for breast cancer using tamoxifen.

Attitude to Health↗
PubMed1991

High total dose 5-fluorouracil treatment during pregnancy.

Experience with systemic chemotherapy in the treatment of the pregnant patient with metastatic breast cancer is limited. Most available reports review the use of single agents and those of combination chemotherapy deal predominantly with hematologic malignancies. While 5-fluorouracil (5-FU) is a commonly used antineoplastic agent in the treatment of metastatic breast cancer, there is minimal reported experience with this drug in the therapy of pregnant patients. We report here the birth of a normal infant in a woman with metastatic breast cancer treated with cyclophosphamide, adriamycin and high total dose 5-FU.

Adult↗
PubMed1991

Symptoms associated with tamoxifen treatment in postmenopausal women.

Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance.

Breast Neoplasms↗