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Biomedical subjects

R M Elashoff

Publications and source records attributed to R M Elashoff.

At least 37 records · Page 2Linked to original sources

Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.

PURPOSE: To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer. PATIENTS AND METHODS: Two hundred ninety postmenopausal women with localized (stage I to IIIa) breast cancer receiving conventional systemic therapy provided informed consent and were randomized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling. RESULTS: Significantly reduced (P < .001) fat intake (in terms of percent calories derived from fat) was observed in the intervention group versus the control group at 3 months (20.3% +/- 2.4% v 31.5% +/- 2.6%, mean +/- SD, respectively) and maintained throughout 24 months of observation. The 50% reduction in daily fat-gram intake (from 66 +/- 23 to 33 +/- 14 g, P < .001) seen at 6 months was associated with reduced saturated fat, monounsaturated fat, polyunsaturated fat, and linoleic acid (P < .001). Significantly lower body weight was also seen in intervention compared with control patients at all observation periods, resulting in a 3.3-kg weight difference 18 months after randomization (P < .001). CONCLUSION: Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer. This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients.

Aged↗

Assessment of adherence to a low-fat diet for breast cancer prevention.

BACKGROUND: The relationships between self-reported adherence to a low-fat diet in healthy women between the ages of 44 and 69 and a number of correlates of this self-reported behavior were examined in an attempt to improve monitoring of adherence to nutritional intervention trials for breast cancer prevention. METHODS: Dietary fat intake in 87 women who completed 6 months of nutritional intervention was reduced from 38.2 +/- 5.9% to 21.7 +/- 7.8% of total energy intake (P less than 0.005). Reported total calorie intake was reduced by approximately 20%. RESULTS: Body weight decreased by 2.7% from 68.1 +/- 11.2 kg to 66.3 +/- 11.9 kg (P less than 0.05). Fasting total plasma cholesterol levels decreased from 205 +/- 31 mg/dl to 184 +/- 29 mg/dl (P less than 0.05). Fasting plasma triglyceride levels did not change significantly (97 +/- 44 mg/dl vs 101 +/- 55 mg/dl). Relative percentage changes in body weight correlated with percentage changes in dietary fat intake (r = 0.23, P less than 0.05). CONCLUSION: Self-reported changes in dietary behavior correlated significantly with objective changes in body weight and fasting cholesterol in these healthy women encouraged to consume a low-fat diet for prevention of breast cancer.

Adult↗

Patterns of care related to age of men with prostate cancer.

A chart review study was done of 242 Stages A2 to D1 cancer patients to determine whether the age of patients with prostate cancer influenced their physicians' management strategies. Ten hospitals of varying size, medical-school affiliation, and patient socioeconomic status participated in this study. Patterns of prostate cancer care were examined using sets of branching logic standards in the form of criteria maps. A chart-based comorbidity index was used to control for the effect of coexisting diseases on cancer management. Regression models indicated that patient age affected the intensity of both the diagnostic evaluation and therapy, even after controlling for independent factors such as comorbid disease and individual hospital differences. Patients aged 75 years and older had significantly less intensive clinical staging workups and use of surgical and radiation therapies compared with patients aged 65 to 74 years and patients aged 50 to 64 years. In conjunction with similar results noted in studies of elderly patients with other malignancies, these results suggest that age bias is likely to be widespread. Physicians need to consider life expectancy, the ability of the patient to tolerate diagnostic procedures and therapies, and the quality of life in making treatment decisions.

Age Factors↗

A quasi-exact test for comparing two binomial proportions.

The use of the Fisher exact test for comparing two independent binomial proportions has spawned an extensive controversy in the statistical literature. Many critics have faulted this test for being highly conservative. Partly in response to such criticism, some statisticians have suggested the use of a modified, non-randomized version of this test, namely the mid-P-value test. This paper examines the actual type I error rates of this test. For both one-sided and two-sided tests, and for a wide range of sample sizes, we show that the actual levels of significance of the mid-P-test tend to be closer to the nominal level as compared with various classical tests. The computational effort required for the mid-P-test is no more than that needed for the Fisher exact test. Further, the basis for its modification is a natural adjustment for discreteness; thus the test easily generalizes to r x c contingency tables and other discrete data problems.

Binomial Distribution↗

Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes. Analysis of prognostic factors in 1134 patients from the John Wayne Cancer Clinic.

A review of 1134 patients from the John Wayne Cancer Clinic with melanoma metastatic to regional lymph nodes was carried out to evaluate the importance of various prognostic features after lymphadenectomy. Univariate analysis identified the prognostic significance of clinical stage for lesions with a depth of 0.76 to 4.0 mm (p = 0.0018); number of involved nodes (p = 0.0001); Breslow's thickness (p = 0.0487); gender (p = 0.0103); location on an extremity (p = 0.0104); synchronous versus asynchronous detection of nodal metastases (p = 0.0107); age as a continuous variable (p = 0.0670); and unknown primary site (p = 0.088). Multifactorial analysis showed that number of involved nodes (p = 0.0001), extremity location of primary (p = 0.0059), and Breslow thickness (p = 0.0334) maintained their significance, whereas gender (p = 0.0627) and clinical stage (p = 0.0942) were almost significant. The long-term survival of the entire patient population at 5, 10, and 15 years of follow-up was estimated to be 46%, 41%, and 38%. When individual characteristics found to be significant by multivariate analysis were combined into different subsets, there was considerable heterogeneity, with 5-year survival varying from 79% to 14%. To quantify this heterogeneity better, a mathematical model was developed and found to approximate closely the observed survival rates in the heterogenous subsets and in the group as a whole.

Analysis of Variance↗

A note on confidence limits for quartiles with right censored data.

Two new methods are proposed for constructing the confidence limits for quartiles. The small sample behaviour of these two methods is compared with the Jennison and Turnbull modified Brookmeyer-Crowley method at three quartiles. The simulation study indicates that one of the new methods, the smoothed modified reflected method, is preferred over the other methods when the censoring rate is less than 40 per cent while the Jennison and Turnbull method is preferred for higher censoring. The results for the upper quartile are similar to the median. For the lower quartile with small sample and high censoring, semi-infinite intervals may often occur. The correct practice is to permit the semi-infinite intervals without modifying them since it is more informative and gives closer to nominal level coverage.

Computer Simulation↗

The statistical analysis of a carcinogen mixture experiment. III. Carcinogens with different target systems, aflatoxin B1, N-butyl-N-(4-hydroxybutyl)nitrosamine, lead acetate, and thiouracil.

This paper describes factorial experiments designed to determine whether two carcinogens that lead to cancers in different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, aflatoxin B1 (AFLA), N-butyl-n-(4-hydroxybutyl)nitrosamine (NBBN), lead acetate (LA), and thiouracil (THIO) were studied in pairwise combinations. Each of the six possible pairs were studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for single agent studies. Neither synergism nor antagonism was demonstrated in these combined exposure studies. Findings for male and female animals were consistent.

Aflatoxin B1↗

Flaws in mortality data. The hazards of ignoring comorbid disease.

Recent public releases of hospital mortality data have sparked debate over methods to identify poor-quality care. We examined variations among hospitals in patient characteristics known independently to affect the risk of adverse outcomes and focused on patient comorbidity, defined as the state of health at admission apart from the primary diagnosis. Data from a study of 2935 incident cancer patients treated in seven Southern California hospitals revealed substantial variations among hospitals in age, cancer stage, and the burden of comorbid conditions. In the highest-ranked hospital, 17.9% of patients had high levels of comorbidity, compared with 9.3% in the lowest-ranked hospital. The three hospitals with the highest comorbidity were also identified as high-mortality outliers in a recent California report on hospital mortality rates. We conclude that comorbidity must be considered in any hospital quality assessment method based on patient outcome. If it is not considered, variations in referral and admission patterns may be misinterpreted as differences in hospital quality.

Age Factors↗

Thermal dose-response of magnetic-induction thermoradiotherapy.

Sixty-three patients with advanced cancer underwent greater than or equal to 5,000 cGy combined with Concentric Coil magnetic-induction localized hyperthermia. Tumor regression (CR + PR) was compared to thermal dose received, incorporating the premise that hyperthermia response is a function of time as well as temperature. A computer program was developed (after Sapareto and Dewey [2]) which stored minimum tumor temperatures recorded spatially and temporally during treatment and correlated response with T43 (equivalent minutes at 43 degrees C during the first treatment) and CT43 (cumulative T43, computed by multiplying T43 by the actual number of identical subsequent treatments received during the course of therapy). Those who responded--N = 46 (73%)--had significantly higher median thermal doses than those who did not respond. Comparison of T43 and CT43 thermal dose values between responders and nonresponders was significantly different at p values of 0.05 and 0.04, respectively. The data indicate that magnetic-induction hyperthermia and high-dose XRT was an effective treatment combination in advanced disease and that tumor response improved as thermal dose increased.

Combined Modality Therapy↗

Exact versus asymptotic analysis for a matched case-control study.

We compare exact and asymptotic methods for variable selection in matched case-control studies. Data from a study of melanoma among the employees of the Lawrence Livermore National Laboratory illustrate the comparisons. Relative to large sample methods, the exact method almost always yielded larger p-values. The differences in p-values became more pronounced with inclusion of more variables in the logistic model. Thus, when the sample size is not large, and there are many covariates under study, use of the exact method tends to select more parsimonious models and avoids overfit of the data.

Algorithms↗

The statistical analysis of a carcinogen mixture experiment. II. Carcinogens with different target organs, N-methyl-N'-nitro-N-nitrosoguanidine, N-butyl-N-(4-hydroxybutyl)nitrosamine, dipentylnitrosamine, and nitrilotriacetic acid.

This paper describes factorial experiments designed to determine whether two carcinogens that act on different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, N-methyl-N'-nitrosoguanidine (MNNG), N-butanol-N-butylnitrosamine (NBBN), nitilotriacetic acid (NTA), and dipentylnitrosamine (DPN) were studied in pairwise combinations. Each of the six possible pairs was studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for single agent studies. Antagonism was demonstrated in some chemical mixtures containing NTA. Other chemical mixtures did not interact. Findings for male and female animals were generally, but not always, in agreement.

Animals↗

Evaluation of three biochemical markers for serially monitoring the therapy of small-cell lung cancer.

A number of biochemical markers have been proposed for monitoring the therapy of small-cell lung cancer (SCLC). This report reviews the experience at a single institution using three biochemical markers, alpha-1-acid glycoprotein (AGP), carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH), for serially monitoring the therapy of patients with SCLC. AGP measurements identified limited-disease patients more frequently than LDH or CEA, and a combination of markers (AGP and LDH) improves the accuracy of correctly classifying patients with active disease. Each of the markers correctly tracked the clinical response to therapy in approximately two thirds of the subjects. The use of a combination of markers should be considered for monitoring the therapy of SCLC in future clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

Statistical analysis of a carcinogen mixture experiment. I. Liver carcinogens.

This paper describes factorial experiments designed to determine whether 2 liver carcinogens act synergistically to produce liver cancers in Fischer 344 rats. Four hepatocarcinogens, cycad flour, lasiocarpine (CAS: 303-34-4), aflatoxin B1 (CAS: 1162-65-8), and dipentylnitrosamine (CAS: 13256-06-9), were studied in pairwise combinations. Each of the 6 possible pairs was studied by means of 4 X 4 factorial experiment, each agent being fed at zero and at 3 non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for one-at-a-time studies. Antagonism was not discovered in any chemical mixture. Some chemical mixtures did interact synergistically. Findings for male and female animals were generally, but not always, in agreement.

Aflatoxin B1↗

Splenomegaly in mice following exposure to ambient levels of ozone.

Female strain A/J mice were exposed to 0.31 ppm (608 micrograms/m3) ozone continuously for 103 h every other week for 6 mth. Following an additional period of 5 mth in a filtered air environment, animals were killed and examined for evidence of altered spleen weight. It was observed that animals exposed to ozone had a greater spleen weight, and spleen to body weight ratio than air-breathing controls. In some of the ozone-exposed mice, pronounced splenomegaly was noted. Increased spleen weight appears to be another example of an extrapulmonary effect of ozone inhalation.

Animals↗

Murine lung carcinogenesis following exposure to ambient ozone concentrations.

Inbred strain A/J mice, responsive to the chemical induction of pulmonary adenomas, were used to assess any of several roles that the photochemical air pollutant ozone might play in lung carcinogenesis. In separate experiments, animals were exposed to two concentrations of ozone (0.31 +/- 0.01 and 0.50 +/- 0.02 ppm) intermittently for a 6-month period, to evaluate the potential of ozone to act as either a pulmonary carcinogen, a tumor promoter, or an inhalant capable of increasing lung tumor yield when exposure was in conjunction with a pulmonary carcinogen, urethane. Statistical analyses of results indicated that ozone exposure at both concentrations caused an increase in lung tumor number relative to clean air controls, but that ozone was not an effective tumor promoter under the conditions of our protocol. When ozone exposure immediately preceded treatment with urethane (CAS: 51-79-6), animals were at increased risk for the development of lung adenomas.

Adenoma↗

Three therapeutic communities. A prospective controlled study of narcotic addiction treatment: process and two-year follow-up results.

The efficacy of three different residential therapeutic communities for male veterans addicted to heroin was studied, comparing 181 subjects who were randomly assigned to one of the communities with 166 subjects briefly hospitalized only for the treatment of withdrawal symptoms. At two-year follow-up, subjects from both a professionally staffed community and a peer confrontation community were found significantly more likely than the withdrawal-only group to be working or attending school and less likely to have been convicted of a crime. An eclectic program employing both professionals and paraprofessionals was not found to exceed the withdrawal-only group on any of the major outcome variables. The two relatively successful communities, although different in structure and style, were both perceived by their residents to have greater program clarity, order, staff control, and orientation to personal problems than the unsuccessful program.

Adult↗

Monitoring the therapy of lung cancer with alpha-1-acid glycoprotein.

Alpha-1-Acid glycoprotein is an acute-phase serum protein which is found in increased amounts in patients with a variety of cancers. This paper describes the application of discriminant analysis to the comparison of plasma levels of alpha-1-acid glycoprotein in 95 patients with lung cancer and 84 patients without known cancer. Using this technique, alpha-1-acid glycoprotein measurement yielded a sensitivity of 89% and specificity of 84% in the detection of active lung cancer. In addition, a new method for analysis of serial tumor marker data is presented which demonstrates that normalization of alpha-1-acid glycoprotein levels during antineoplastic therapy correlates with a significantly prolonged relapse-free survival in lung cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

Immunotherapy with biochemically dissociated fractions of Propionibacterium acnes in a murine ovarian cancer model.

The antitumor effect of two strains of Propionibacterium acnes (PAI and PAII) and chemically derived fractions from the whole bacterial cell were studied using a murine ovarian teratocarcinoma (MOT) model. When injected i.p. in high doses (700 to 1400 micrograms/mouse), both strains produce survival of a significant proportion of tumor-bearing mice (30 to 90%). On a weight to weight basis, however, PAI was significantly more effective than PAII. PAI and PAII were extracted using pyridine, which yielded four fractions, i.e., pyridine-extracted strains PAI and PAII (PA-PEI and PA-PEII, respectively) which are composed of the cell wall material extracted by pyridine, and the residues of PA-PEI and PA-PEII (PA-RI and PA-RII, respectively) which are composed of the residue material following the chemical extraction. The chemical composition of PA-PEI was different from that of PA-PEII (the latter had proportionately three times as many carbohydrates and one-third of the protein content of the former) and so were their antitumor properties in the MOT model. PA-PEI had markedly reduced antitumor effect when compared to the untreated cell on a per weight basis. Furthermore, curability was only seen when using a high dose (1400 micrograms/mouse). By contrast, the cell wall components extracted by pyridine from PAII (PA-PEII) had powerful antitumor effects, i.e., greater than 50% of mice given 1400-micrograms injections survived. The material contained in PA-PEII was further fractionated on the basis of its organic solubility in chloroform:methanol solvent. The water-soluble and solvent-insoluble fractions retained most of the antitumor effects of PA-PEII, while the water-insoluble and solvent-soluble fractions were only moderately effective, suggesting that the active moiety(ies) was associated with the nonlipid components of this fraction. Both residue fractions (PA-RI and PA-RII) were as effective on a per weight basis in controlling the growth of 10(5) tumor inoculum as were whole untreated cells. However, periodate oxidation of PA-RI resulted in complete loss of its antitumor effects. When surviving mice that had no evidence of tumor persistence following a tumor challenge (10(5) MOT cells) and i.p. treatment with PA were subsequently rechallenged with 10(4) tumor cells, survival was significantly prolonged, as compared to tumor-challenged (10(4) MOT) naive mice. In addition, 10 to 20% of these rechallenged mice had complete eradication of the tumor inoculum (no evidence of disease for greater than 120 days).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗