Screening mammography in clinical practice. A complex activity.
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Biomedical subjects
Publications and source records attributed to R R Love.
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We conducted a 2-year, randomized, double-blind, placebo-controlled toxicity trial of therapy with tamoxifen (10 mg twice a day) in 140 postmenopausal women with a history of breast cancer and histologically negative axillary lymph nodes. These women had been treated with surgery with or without radiotherapy. At a 3-month evaluation, tamoxifen-treated women showed a significant decrease in fasting plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which persisted at 6- and 12-month evaluations. During the first 12 months, plasma triglyceride levels increased; small but significant decreases in high-density lipoprotein cholesterol (HDL) were observed in tamoxifen-treated women, but ratios of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol changed favorably. While data relating lipid/lipoprotein profiles and cardiovascular disease are limited in women, current evidence suggests that total cholesterol and possibly low-density lipoprotein cholesterol are risk factors. We conclude that during the first 12 months of treatment, tamoxifen exerts a favorable effect on the lipid profile in postmenopausal women with early stage breast cancer.
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Tissue activity levels of ornithine decarboxylase (ODC) have been suggested to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. Supplemental dietary calcium has been hypothesized and reported to suppress colonic epithelial-cell proliferation. We measured sigmoid and rectal mucosal ODC activity levels in 45 healthy, disease-free subjects with strong family histories of colorectal cancer before and after 2 months, during which daily dietary supplementation with calcium carbonate (to provide 600 mg calcium base) was taken. Although the mean ODC activity levels decreased in both sigmoid and rectal specimens, these changes were small in relation to the standard deviation and were not statistically significant. These data suggest that the magnitude of dietary calcium intake does not significantly influence sigmoid-rectal mucosal ODC activity levels and that ODC measurements may not be a useful intermediate endpoint for interventions designed to interrupt the colon carcinogenic sequence.
Cancer control investigations in the United States rarely use population-based registries as a resource for recruitment. A placebo-controlled, double-blind, randomized toxicity trial of tamoxifen was conducted among postmenopausal women with node negative breast cancer. To achieve the accrual goal of 140 subjects in this single institution study, the Wisconsin Cancer Reporting System (WCRS), a population-based cancer registry, was used. Registry information from the last 9 years was used to identify 3,585 women who met the study criteria with respect to age, stage, and previous therapy. The vital status of identified women was confirmed using Wisconsin state death records. For identified cases, rosters were prepared and sent to the physician with a cover letter and study description. The physicians were asked to update the list and, if appropriate, to sign letters to potentially eligible and interested women. Thirty-eight percent of women receiving a letter and study information from their physicians contacted the study office about participation. Eighteen months from its initiation, 140 women were entered on study. This successful use of a population-based cancer registry illustrates an efficient recruitment method which could be modified for other cancer control/chemoprevention trials.
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The traditional method of instruction for preclinical medical students is lecture, where the role of the student is passive. The practice of clinical medicine is a problem-solving endeavor. It requires the accumulation of information from diverse sources, its analysis, synthesis, and application, as well as the ability to work together with other health professionals to communicate critical information to patients. We have, therefore, adopted these activities in the teaching of a neoplastic diseases course. Every student is assigned to a four-member student team which has to organize and present to the entire class a succinct 10- to 15-minute minilecture on an assigned topic, along with a one-page typewritten synopsis. A second assignment for every student is to prepare a five-minute presentation on a specific question for discussion by a small group. Clinical correlation sessions involving analysis of patient problems provide a third teaching method. The course examination is short essay; half of the questions are given in advance. On postcourse evaluations, students have ranked the clinical correlation sessions as most effective, and the discussion groups as least effective. The entire-class presentations were information dense and accurate, but often unclear as to major points and too long, eliciting harsh criticism from colleagues. Students expressed unfounded concern that such presentations missed critical material, and some students felt overly stressed by this assignment, while others felt deprived of being taught by "experts." The lack of uniform answers by discussion group leaders was listed as the major problem with the small group method. The essay examination received high ratings.
Ocular toxicity is a common, but poorly understood, sequela from CMF chemotherapy. We investigated this toxicity in patients receiving CMF therapy. Detailed interviews in 210 patients revealed that new, unpleasant ocular symptoms developed in 42% of patients receiving CMF, in 39% of subjects receiving other regimens containing 5-fluorouracil (5-FU), and only in 18% of subjects receiving a variety of chemotherapy regimens not containing 5-FU. CMF-associated ocular symptoms usually consisted of mild to marked tearing, ocular pruritus, and/or burning. These toxicities usually began 11-17 days after starting a cycle of CMF and lasted for 10-15 days. 5-FU was detected in the tears of 12 tested patients within several minutes after intravenous 5-FU (peak concentrations as high as 60 micrograms/ml). 5-FU tear concentrations did not correlate with the presence or absence of ocular toxicity. There is no established antidote for this toxicity although some patients have reported subjective benefit from cryotherapy, applied around the period of 5-FU injections, or cromolyn sodium eye drops.
Within the imaging literature, the super bone scan has emerged as a distinct type of bone scan with a specific differential diagnosis. Previous reviews have included prostate, breast, bladder and colon cancer, and lymphoma among the causes of a super bone scan but have not included stomach cancer. We report a super bone scan caused by late recurrence of stomach cancer in the bone marrow. Because the management of stomach cancer is significantly different than the management of other causes of a super bone scan, the distinction is clinically relevant. We conclude that stomach cancer should be considered in the differential diagnosis of a super bone scan.
Chemotherapy side effects, patient distress, and patient-practitioner communication were evaluated in an inception sample of 238 patients with breast cancer or malignant lymphoma. Participants were interviewed at five points during their first six cycles of therapy, and a subsample kept brief daily symptom diaries. Nausea, hair loss, and tiredness were each experienced by more than 80% of patients. By cycle 6, 46% of patients had thoughts about quitting therapy, but only a few had told medical staff. Patients' ratings of the objective difficulty of treatment increased over time, varied by treatment regimen, and were predicted by the experience of side effects, with the number of different side effects serving as the best predictor. In contrast, emotional distress was less sensitive to the directly assessable characteristics of treatment. Communication between patient and practitioner was found to be inadequate in a number of respects (i.e., patients did not fully anticipate the toxicities of treatment and did not report their concerns to medical staff). Communication may be impeded by inaccuracies in a patient's recall of treatment difficulties and by a patient's inability or unwillingness to attend to all presented information. More frequent opportunities for patient-practitioner discussion are necessary.
Ornithine decarboxylase (ODC) catalyzes the formation of putrescine from ornithine, which is the first step in the pathway of mammalian polyamine biosynthesis. Tissue activity levels of ODC have been suggested to be a marker of risk for colorectal cancer in hereditary polyposis and in adenoma formers. We analyzed ODC activity in rectal and sigmoid colon mucosal biopsies obtained at 10 cm and at 30 cm in 40 healthy, colon cancer risk factor-free adults following three endoscopic preparation regimens: 1) no special preparation; 2) two phosphate enemas; and 3) "Colyte" lavage preparation 12 hr previously. Levels of ODC, measured in fresh tissue, were approximately twofold higher for enema preparation vs. no preparation (for log-transformed data: sigmoid, P less than 0.0001; rectum, P = 0.0001) and for enema preparation vs. lavage (sigmoid, P = 0.0002; rectum, P = 0.008). Lavage and no preparation ODC levels were not significantly different. ODC activity levels ranged from 0.00 to 352.96 pmol/mg/hr.
Tamoxifen citrate, the most extensively evaluated antiestrogen, acts primarily as a cytostatic agent by binding to the estrogen receptor. In rodent mammary model systems, when tamoxifen is given continuously after exposure to a carcinogen, the majority of expected tumors do not develop. In humans, adjuvant tamoxifen therapy, particularly when given for several years, is associated with significant improvement in relapse-free, and, in some studies, absolute survival. These benefits are achieved without major clinical toxicity and have led to suggestions that the use of tamoxifen as a chemopreventive agent in breast cancer be evaluated. In considering timing, optimal study population, study design, and methods for a chemoprevention trial using tamoxifen, the need for further data on the pharmacologic, biologic, and symptomatic effects of this agent becomes clear. Studies addressing this need are in progress and combined with ancillary data developed from ongoing adjuvant studies, should provide the critical information within the next few years.
Since its introduction into clinical use in the early 1970s, the synthetic antiestrogen tamoxifen citrate has been shown to contribute to the control of human breast cancer in increasingly significant ways. While its mechanisms of action and pharmacology are incompletely understood, tamoxifen appears to act predominantly by blocking the action of estrogen by binding to the estrogen receptor. Clinical trials of tamoxifen for 1 to 2 years in primary breast cancer demonstrate consistent beneficial effects on disease-free survival, but only suggested beneficial effects on survival. Routine use of adjuvant tamoxifen for 5 years or more will depend on the results of ongoing large clinical trials of efficacy and detailed studies of unknown biological effects on other tissues.
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Optimal community programs in cancer prevention and detection have as their goals the lowering of incidence, complications, and mortality from cancer in a population, and are characterized by efficiency, self-sustainability, and generalizability. Programs fall into three categories according to their degree of integration into the normal health-care system. "Extra-systemic" programs are temporary demonstration activities, which may have research goals. "Quasi-systemic" activities include public health department programs, worksite programs, and specialized centers such as breast screening centers. "Systemic" activities involve counseling and screening in routine medical practice. The greatest potential for reaching the indicated goals lies in facilitating systemic activities by allowing primary-care practitioners to define their own prevention goals, to make changes in their practices to address these goals, and to educate consumers of the need to demand preventive services.
Susceptibility to motion sickness has been demonstrated to be a predictor of anticipatory nausea in cancer patients receiving chemotherapy. However, previous research did not test whether motion sickness increases anticipatory nausea only by increasing the base rate of posttreatment nausea and vomiting (which has traditionally served as the unconditioned stimulus in the conditioning model for anticipatory nausea) or, alternatively, whether motion sickness might facilitate the association of external stimuli to posttreatment nausea and vomiting. Using two different analytic approaches--a series of logistic analyses that controlled for drug-induced nausea and vomiting following the initial injection, along with an event history analysis which allows for updating on the posttreatment nausea and vomiting factors--motion sickness was found to be an independent predictor of anticipatory nausea. Further, the predictive power of motion sickness is also independent of the effects of pretreatment anxiety, taste during injection, and age.
While in limited animal studies tamoxifen is reported to protect against loss of bone mineral, data in humans are lacking. We measured bone mineral density (BMD) using single photon absorptiometry at the radius and dual photon absorptiometry at the lumbar spine in breast cancer patients treated with chemotherapy at our institution. In this group, 37 women were not treated with tamoxifen (NT) and 48 women were treated with tamoxifen (T) for at least two years. Younger age, greater weight and height, premenopausal status, and shorter time since menopause were found to be significant predictors of greater BMD. Tamoxifen-treated women had been postmenopausal for more years (p = 0.012). Regression analyses used to adjust for differences in risk of bone loss did not reveal significant differences in BMD between the two groups of women. For the postmenopausal women (27 NT and 34 T subjects), the adjusted mean BMD (g/cm2) at the spine was 1.11 (NT), 1.11 (T) (p = 0.93); and at the radius 0.63 (NT), 0.62 (T) (p = 0.30). This limited retrospective study suggests that tamoxifen does not have 'anti-estrogenic' effects on BMD.