The feasibility of testing experimentally the dietary fat-breast cancer hypothesis.
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Adult↗
Biomedical subjects
D Tritchler
Publications and source records attributed to D Tritchler.
Variability in nursing workload within CMGs (case mix groups).
This study examines the differences in workload estimates of three patient classification systems in nursing, within selected Case Mix Groups (CMGs). The amount of variation explained by selected patient-specific variables within CMGs on average nursing workload by each system is also analyzed. Results show that, when patient classification data are used to explain nursing time within the Diagnosis Related Group (DRG) context, absolute hours of care estimates of the various systems may not be equivalent. This inequality may result in biased budget review practices unless relational statements are developed between systems.
Canada↗
Plasma lipids in premenopausal women with mammographic dysplasia.
Epidemiological evidence indicates that mammographic dysplasia is associated with an increased risk of breast cancer, particularly in premenopausal women. To examine biochemical associations with mammographic dysplasia we have compared premenopausal women with different patterns of the breast parenchyma on mammography. One group had extensive radiological dysplasia (n = 30) and the other no dysplasia (n = 16). Both groups were recruited from mammographic units in the same way and then compared according to epidemiological risk factors, anthropometric measures, nutrient intake and plasma levels of oestradiol, progesterone and prolactin obtained in both follicular and luteal phases of the menstrual cycle as well as total plasma cholesterol and lipid fractions. Women with mammographic dysplasia were found to be leaner, more often nulliparous and to consume more alcohol than women without these radiological changes. Mammographic dysplasia and a family history of breast cancer were found to be independently associated with significantly higher levels of high density lipoprotein cholesterol (HDL-C) after taking into account the possible confounding effects of percentage body fat, parity and consumption of alcohol and dietary fat. Triglyceride levels were also independently associated with a family history of breast cancer. We conclude that further investigation is warranted of the role of plasma lipids in relation to breast cancer risk.
Adult↗
Fish consumption and breast cancer risk: an ecological study.
There is experimental evidence that fish oils protect against mammary carcinogens in animals. However, there has been little investigation of the possible relevance of this finding to breast cancer in humans. We compared breast cancer incidence and mortality rates with estimates of the consumption of fish and other foods and nutrients in the countries for which reliable data are available. The results showed an inverse association between percent calories from fish and breast cancer rates that was consistent with a protective effect. This analysis confirmed the finding of others that dietary fat is strongly associated with international variation in breast cancer rates. It also showed that of the dietary components considered, percent calories from fish was the factor most strongly correlated with breast cancer rates after statistical adjustment for dietary fat intake. This result is therefore in accord with animal experimental data and suggests that the omega-3 fatty acids contained in certain fish may protect against breast cancer.
Analysis of Variance↗
Clinical trial of low-fat, high-carbohydrate diet in subjects with mammographic dysplasia: report of early outcomes.
Despite evidence that dietary fat intake may influence breast cancer risk, there is little information about the effects of dietary fat on the human breast. We have studied the effects of dietary fat on the breast by examining the influence of dietary fat reduction on mammographic dysplasia (nodular or sheetlike areas of radiological density). Subjects with mammographic dysplasia were randomly allocated to a control group, in which they received advice about maintaining a balanced diet (36% of calories as fat), or an intervention group, in which they were taught to reduce dietary fat to a target of 15% of calories. A total of 295 patients consented to randomization, and after 1 year, 20% of the intervention group and 5% of the control group had dropped out (failed to keep appointments and provide nutrient data). The remaining patients closely adhered to the dietary goals of the study as assessed by food records, chemical analysis of duplicate meals, and serum cholesterol measurements. Comparison of mammograms before and after 1 year of dietary fat reduction shows no significant influence on the extent or density of mammographic dysplasia. Surgical biopsies performed in subjects after entry in the study showed five cancers in the control group and two cancers in the intervention group; this total of seven cancers is four times the number expected. These data show that clinical trials of the effects of dietary fat reduction on breast cancer risk are feasible and that long-term compliance with a low-fat diet can be achieved, and they confirm that the patients selected because they had mammographic dysplasia had increased risk of breast cancer.
Adult↗
Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy.
21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.
Adult↗
Hemopoietic colony growth-promoting activities in the plasma of bone marrow transplant recipients.
Plasma samples were obtained from 34 bone marrow transplant (BMT) recipients before and after administration of the preparative regimen and tested for their ability to promote and/or support growth of hemopoietic colonies. The ability of plasma samples to promote colony formation on their own was tested on normal nonadherent target cells without addition of exogenous growth factors. The growth-supporting activity was examined in the presence of medium conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM) and/or erythropoietin (EPO). A series of kinetic changes was routinely observed. Pretransplant samples rarely gave rise to colonies without addition of exogenous growth factors. Plasma samples obtained after completion of the preparative regimen demonstrated increments of growth-promoting activities for megakaryocyte and granulocyte-macrophage progenitors (CFU-Meg and CFU-GM), respectively, that peaked between 7 and 21 d after transplantation. By day 30, activity levels of some patients had returned to pretransplant values, whereas in other patients, activities remained elevated. Persisting activity levels were associated with delayed engraftment. In contrast, activities for progenitors committed to erythropoiesis (BFU-E) and pluripotent precursors (CFU-GEMM) were only rarely observed. The activities were independent of febrile episodes. Their growth-promoting influence on CFU-GM could be neutralized completely by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. These data suggest that at least some of the observed activities in post-BMT plasma are related to GM-CSF. The growth-supporting activities of pretransplant plasma samples are lower than normal plasma when tested on CFU-Meg and CFU-GM. The growth-supporting activities improved transiently within the first month after BMT. A decline during the second and third month was followed by a gradual return to activity levels that were comparable to normal plasma. The effects of these plasma samples on BFU-E and CFU-GEMM were assessed with PHA-LCM and EPO. Similar to CFU-Meg- and CFU-GM-supporting capabilities, they improved transiently after BMT with a return of normal support function after 5-6 mo. The observed endogenous production of growth-promoting and growth-supporting activities for hemopoietic progenitors may serve as a background to design clinical trials for the timely administration of recombinant hemopoietic growth factors to BMT recipients.
Animals↗
Choosing a risky treatment.
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Bone Marrow Transplantation↗
The three-decision problem in medical decision making.
Medical researchers and policy makers face decisions that require a choice from among two or more alternatives. Whereas traditional hypothesis tests cannot always serve the needs of the practitioner who needs to make a decision, a problem formulation that assigns losses to various incorrect decisions offers several advantages. With three possible decisions this approach offers a precise representation of the pragmatic and explanatory views of decision making. It enables the investigator to incorporate in the problem specification his attitudes about the seriousness of various errors by guiding him, before he sees the data, to a choice of asymmetric tail probabilities. It also suggests a reformulation of the P-value that can accommodate some of the difficulties practitioners face.
Biometry↗
Clonogenic hemopoietic precursors in bone marrow transplantation.
Multilineage and single-lineage hemopoietic precursors were studied in 102 bone marrow transplant recipients and their respective donors to determine their contribution to clinical outcome as measured by time to engraftment and survival. The patient population was heterogenous with respect to diagnosis and disease status. They included individuals with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), aplastic anemia, and a few other hematopoietic malignancies. The frequency of various clonogenic precursors in the normal donor population varied considerably. The data yielded a symmetrical distribution. In contrast, most bone marrow transplant recipients presented with significantly reduced numbers of clonogenic cells before transplantation, resulting in skewed distribution profiles. Serial studies of recipients demonstrated a significantly lower than normal level of clonogenic precursors even 3 and 4 years after transplantation. The median values and distribution profiles approximated those observed before transplantation but did not return to measurements obtained for normal donors. Patients with ALL deviated from this pattern. The median values and distribution profiles of clonogenic precursors before transplantation approximated the pattern of normal donors. The frequency of clonogenic progenitors after transplantation, however, remained significantly lower than that of their respective donor or pretransplant values. Cell cycle studies performed after normalization of peripheral blood hematopoietic parameters demonstrated for most recipients that a higher than normal proportion of multipotent cells was in S-phase (P = .011). By univariate and multivariate approaches, clonogenic precursors and clinical parameters were assessed for their contributions to clinical outcome as measured by time to engraftment and survival time. The number of nucleated cells in the transplant inoculum contributed to survival independent of other risk factors. Patients with a higher cell load had a higher probability of surviving than did patients with a lower cell concentration in the transplant inoculum (P = .042). The frequency of clonogenic precursors in the transplant inoculum altered neither survival nor time to engraftment. The time to engraftment was significantly influenced by the frequency of clonogenic megakaryocyte precursors (CFU-M) observed in recipients prior to transplantation (P = .003). Patients with high values engrafted faster than did patients with a low frequency of CFU-M. This was independent of both diagnosis and disease status of the patients at time of transplantation.
Adolescent↗
Torque placed by dentists on prefabricated threaded posts.
Thirty-one dentists were tested relative to the optimal and maximum amount of torque they could deliver to posts in teeth. The mean for the optimal amount of torque was 15.55 ounce-inches, and the mean for the maximum amount of torque was 35.29 ounce-inches. Female dentists showed a statistically significantly lower mean difference of 24.5 ounce-inches on the maximum torque test.
Adult↗
Response to hydrocortisone of blast progenitors in acute myeloblastic leukemia: an aspect of lineage infidelity.
The blast population in acute myeloblastic leukemia (AML) contains cells capable of forming blast-cell colonies in culture. The purpose of this study was to measure the effects of hydrocortisone on this process, using two end-points. First, we measured the effects of increasing concentrations of hydrocortisone on the primary plating efficiency of T-lymphocyte-depleted blast cell preparations from AML peripheral blood. Second, colonies forming in the presence or absence of the hormone were pooled and replated; changes in the plating efficiencies (secondary plating efficiency or PE2) of these suspensions reflected the effect of the hormone on blast progenitor self-renewal. For comparison, we measured the hydrocortisone dose response curves for normal granulopoietic and T-lymphocyte colony-formation. The latter showed little individual variation; T-lymphocyte colony-formation was regularly sensitive to the hormone while granulopoietic colony-formation was resistant. In contrast, wide variations were found in the hydrocortisone dose response curve for blast from 24 patients with AML (FAB 1-6). A significant association was found between successful remission induction and resistance to hydrocortisone in 24 treated patients. The association was maintained when the data was stratified by other risk factors, including PE2 and the presence of blasts bearing immunologically-defined markers of more than one differentiation lineage (lineage infidelity). We propose that sensitivity to hydrocortisone may reflect the passage of blast cells through lymphopoiesis-associated components of differentiation programs. From this point of view, the poor prognosis associated with sensitivity of blast progenitors to hydrocortisone may be similar to the response-failure of patients whose blasts exhibit lineaged infidelity when tested with immunological procedures.
Adolescent↗
Colony growth and self renewal of plasma cell precursors in multiple myeloma.
Culture conditions that support the growth of multi-and single-lineage hemopoietic colonies are also able to give rise to large myeloma colonies from bone marrow and peripheral blood samples of some patients with multiple myeloma. The culture system was used to determine the frequency of hemopoietic precursors and clonogenic myeloma progenitors in 71 patients with multiple myeloma studied in various clinical phases of the disease. The frequency of normal hemopoietic precursors in patients with benign monoclonal gammopathy and smoldering myeloma were indistinguishable from normal controls. Myeloma colonies were not observed in these subgroups. In contrast, patients with active disease showed significantly reduced hemopoietic colony formation, even before the initiation of therapy. A further reduction was demonstrated for patients with acute phase disease. A correlation between the frequency of hemopoietic colonies and the concentration of plasma cells in the plated sample was not observed. Large myeloma colonies with recloning potential were identified in cultures of specimens derived from 14 of the studied patients. These colonies were most frequently (ten cases) obtained from patients who had entered the acute phase of the disease. These patients manifested marrow failure (pancytopenia) and their marrow had a limited capacity to generate normal hemopoietic colonies. Three of the patients that formed myeloma colonies were studied in chronic phase following chemotherapy and one patient was examined at diagnosis. The myeloma colonies were composed exclusively of cells characterized by the same M protein as the patient. Some of the cells within the colonies retained their ability to self renew extensively, as demonstrated by serial recloning studies. Colonies derived from six of the patients are now propagated in semisolid and liquid medium for as many as nine to 34 generations. Patients that form myeloma colonies under these culture conditions represent a high-risk group with significantly shorter survival than patients not able to give rise to myeloma colonies. A Cox proportional hazards model was fitted to the data to determine the prognostic role of myeloma colony growth in culture after accounting for the influence of other well established risk factors, such as concentration of plasma cells and disease status. The analysis indicated that myeloma colony growth in culture serves as a strong and independent predictive indicator of poor clinical prognosis.
Actuarial Analysis↗
Criteria of tumor response used in clinical trials of chemotherapy.
We have studied 61 published reports of trials of cancer chemotherapy to evaluate the criteria for tumor response that were used and the adequacy of their description in the publication. Our sample comprised recent articles published in three major journals that addressed the influence of chemotherapy on patients with recurrent or metastatic colorectal cancer, non-small cell lung cancer, and head and neck cancer. Incomplete information was sought through a questionnaire mailed to the senior author of each paper, and 48 of them responded. We conclude that: no article contained all of the information required to define precisely criteria for tumor responses; criteria for tumor response are variable; and differences in response criteria contribute to the wide variation in reported rates of tumor response. Meaningful intercomparison of clinical trials will require the establishment of uniform criteria for assessing and reporting the response of tumors to chemotherapy.
Antineoplastic Agents↗
The effect of 5-azacytidine and its analogues on blast cell renewal in acute myeloblastic leukemia.
Blast cells from patients with acute myeloblastic leukemia were exposed to 5-azacytidine (5-aza) and its analogues 5-aza 2'-deoxycytidine (5-aza-dr) and 6-azacytidine (6-aza). Simple negative exponential survival curves were obtained for the three drugs, but the sensitivity varied; 5-aza-dr was most toxic, 6-aza was least toxic, and 5-aza was intermediate. Colonies surviving drug exposure were replated; 5-aza and 5-aza-dr were found to increase secondary plating efficiency, whereas 6-aza was inactive. The findings provide indirect evidence for a role for DNA methylation in the regulation of blast cell self-renewal.
Azacitidine↗
Phase II study of PALA, amsacrine, teniposide, and zinostatin in small cell lung carcinoma (EST 2579).
Eighty-two patients with small cell lung carcinoma refractory to standard chemotherapy were entered in this phase II randomized study of PALA, amsacrine, teniposide, and zinostatin. Of the 66 evaluable patients, one partial response occurred among 17 patients treated with teniposide and no responses occurred with the other drugs. Two patients each treated with amsacrine and teniposide experienced life-threatening hematologic toxic effects and one patient treated with zinostatin died of thrombocytopenic pulmonary hemorrhage. The overall median patient survival was 9.6 weeks. Weight loss greater than or equal to 5% prior to therapy, extensive disease, and a nonambulatory status were associated with poor survival.
Aminoacridines↗
Phase II study of PALA and PCNU in the treatment of non-small cell lung cancer (EST 2580): an Eastern Cooperative Oncology Group study.
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Aged↗
G6PD isoenzyme analysis of myeloid and lymphoid cells in human multilineage colonies.
Some multilineage hemopoietic colonies contain, in addition to myeloid cells, T lymphocytes. These proliferate extensively in liquid suspension culture under the influence of a T cell growth factor provided by phytohemagglutinin-T cell-conditioned medium (PHA-TCM). The clonal origin of these myeloid and lymphoid components was investigated by determining the glucose-6-phosphate dehydrogenase (G6PD) isoenzyme types of multilineage colonies grown from peripheral blood of 4 G6PD heterozygous normal volunteers. The G6PD assay is sufficiently sensitive to detect enzyme concentrations contributed by as few as 30 granulocytes and erythroblasts, 4-6 megakaryocytes, 2-3 macrophages, and 50-100 T cells. T cell components can be detected even if myeloid cells are present in 10-20-fold excess. A small number of multilineage colonies with T cells produced a single G6PD isoenzyme on direct analysis and after expansion in liquid culture. This observation supports the view of a common progenitor for myeloid and lymphoid cells in the peripheral blood of normal adults.
Adult↗