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R L Prentice

Publications and source records attributed to R L Prentice.

At least 55 records · Page 3Linked to original sources
PubMed1985

Rationale and design of cancer chemoprevention studies in Seattle.

Three cancer prevention trials are currently in their early phases at The Fred Hutchinson Cancer Research Center, the University of Washington School of Public Health and Community Medicine, and the Swedish Hospital. All 3 studies are randomized and placebo controlled. One large-scale study involves the daily administration of retinoids to persons with asbestos-related lung disease in an attempt toward reduction of their high risk for bronchogenic carcinomas and mesotheliomas. A second study involves administration of the same agents to long-term heavy smokers; a substantial feasibility and toxicity pilot study will precede a full-scale prevention trial. In the third trial, folic acid administration is evaluated in relation to the progression and regression of cervical dysplasia among women with abnormal Pap smears. We report here the rationale and the design for these 3 studies.

Asbestosis↗
PubMed1984

Serum cholesterol, other risk factors, and cardiovascular disease in a Japanese cohort.

The relationship of serum cholesterol and other risk factors to cardiovascular disease was investigated in a 16-year cohort of 16,711 residents of Hiroshima and Nagasaki. Examined in detail were the relationship of serum cholesterol, and the joint relationships of serum cholesterol, systolic blood pressure, diastolic blood pressure, and other risk factors to coronary heart disease (CHD), cerebral infarction (CI), and cerebral hemorrhage (CH). Baseline and biennially collected risk factor data were analyzed. The latter type of measurement permitted separate investigation of both the short-term and long-term effects of cholesterol measurements. In both types of analyses, both serum cholesterol and blood pressure showed strong associations with CHD incidence. In particular, there were strong associations with short-term and delayed CHD incidence. Furthermore, the association of cholesterol with short-term CHD incidence could not be explained by its association with delayed CHD incidence, or vice versa. Multivariate analyses that also included several other risk factors (smoking habits, clinical diagnosis of diabetes mellitus, left ventricular hypertrophy or strain on electrocardiogram, relative body weight, hematocrit, and proteinuria) for which data were available showed such risk factors to be of lesser, but generally non-negligible, importance in this population. In the case of CH and CI, serum cholesterol was found to be weakly or not at all related to incidence of either disease while blood pressure remained a strong correlate. For CI some suggestion of a statistical interaction between blood pressure and serum cholesterol was found. Discussed are implications for theories of disease pathogenesis for CHD, CI and CH.

Adult↗
PubMed1984

HLA and disease: relative-risk regression methods and multiple testing considerations.

This paper discusses certain statistical issues arising in an analysis to relate HLA-B antigens to the incidence of graft-versus-host disease in a clinical study. The Cox regression method is used to develop a global test of the hypothesis of no association and to produce estimated relative-risk factors corresponding to the presence of each particular allele. Multiple-testing considerations are central to any attempt to identify pairs of alleles having significantly different relative-risk factors. A number of simultaneous-testing approaches are considered including cumulative P-value plotting and a direct simulation of the null distribution of the maximum pairwise ratio.

Anemia, Aplastic↗
PubMed1984

On the use of case series to identify disease risk factors.

Methods to identify disease risk factors from a series of cases are considered. These include methods that compare risk factor levels among diagnostic categories and methods that relate risk factor levels to age at diagnosis, with a single diagnostic category. Statistical aspects considered include modelling assumptions, parameter identifiability, hypothesis-testing efficiency, assumptions concerning unsampled diagnostic categories and requirements for risk factor data and confounding factor data. It is argued that methods to identify risk factors using data on a single diagnostic category involve such strong assumptions that they have limited usefulness. Analyses that compare risk factor levels among diagnostic categories, on the other hand, should continue to play an important role in epidemiologic research, though there are important limitations in relation to analyses involving disease-free controls.

Age Factors↗
PubMed1984

Correlation of two in vitro tests with clinical response to immunosuppressive therapy in 54 patients with severe aplastic anemia.

Two in vitro tests were applied to 54 consecutive patients with severe aplastic anemia who were treated in Seattle with antithymocyte globulin. In the first test, peripheral blood mononuclear cells were collected from each patient before antithymocyte globulin therapy and then treated with a panel of monoclonal antibodies and complement. The treated peripheral blood mononuclear cells were assayed for erythroid burst-forming units (BFU-E). This test was designed to determine whether removing various subpopulations of peripheral blood mononuclear cells would increase the number of detectable BFU-E. In the second test, peripheral blood was collected within 48 hr after completion of antithymocyte globulin therapy, and cells were immediately assayed for BFU-E without any further treatment. Data from both tests were analyzed to determine whether the in vitro results correlated with patient response to therapy. Binary logistic regression analyses indicate that a modest correlation (p = 0.04) exists between test 1 in vitro results and patient response to therapy. However, the strength of this association appears to decrease as the interval between diagnosis and treatment increases. In contrast, test 2 had a very significant correlation (p = 0.001) with response to therapy among patients diagnosed more than 1 mo prior to treatment, whereas such an association was not apparent among patients treated within 1 mo of diagnosis.

Adolescent↗
PubMed1984

The analysis of chromosomally aberrant cells based on beta-binomial distribution.

Analysis carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extrabinomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extrabinomial variation is accommodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (beta-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the beta-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models.

Chromosome Aberrations↗
PubMed1983

Association between HLA-B antigens and acute graft-versus-host disease.

130 patients with severe aplastic anaemia, conditioned with high-dose cyclophosphamide, showed sustained engraftment of marrow from HLA-identical siblings. Most patients (55%) had no acute graft-versus-host disease (GVHD), 11% had transient grade I, and 34% had moderate to severe (grades II-IV) acute GVHD. The relation between the donors' (and the patients') HLA antigens and the incidence of grades I-IV acute GVHD was explored. There was no association with HLA-A antigens, but a significant correlation with HLA-B antigens. Patients with HLA-B18 had an estimated acute GVHD incidence nearly three times that of other patients, whereas the incidence in the presence of HLA-B8 or HLA-Bw35 was estimated to be about half that in the absence of these alleles.

Acute Disease↗
PubMed1983

Acquired immune deficiency syndrome. A prodromal form.

Only one case of the acquired immune deficiency syndrome (AIDS) has been conclusively documented in Australia despite a large at-risk population and the endemic nature of the syndrome in the United States. In this article, the cases of two homosexual men who had the clinical and laboratory features of a prodromal form of AIDS are presented. Such cases should serve to alert the medical profession and public health authorities to the possible existence of the syndrome in Australia.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protective environment.

One hundred thirty patients with severe aplastic anemia were conditioned with cyclophosphamide for transplantation of marrow from HLA-identical siblings. The patients were selected for the present analysis according to the criterion of sustained marrow engraftment. Of the 130 patients, 97 are now alive between 1.4 and 11 years (median, 5) after transplantation. Twenty-nine of the thirty-three who died had either acute or chronic graft-versus-host disease (GVHD). Our analysis was directed at identifying factors predicting GVHD and survival after transplantation in patients. Our key findings were that moderately severe to severe acute GVHD had a strong adverse influence on survival; that a protective environment significantly reduced mortality, which corresponded in part to a reduction in and delayed onset of acute GVHD; that refractoriness to random-donor platelet infusions at transplantation adversely influenced survival, particularly among patients with acute GVHD; and that increasing age was associated with increased mortality.

Adult↗
PubMed1983

Factors associated with graft rejection after HLA-identical marrow transplantation for aplastic anaemia.

One hundred and seventy-five consecutive patients with severe aplastic anaemia were given high-dose cyclophosphamide followed by marrow grafts from healthy, HLA-identical family members, and 168 lived long enough to show engraftment. In 38 patients the graft was rejected and 29 of these died. This analysis, using a binary logistic regression model, was aimed at identifying factors that predicted marrow graft rejection. Five factors correlated with graft rejection: (1) previous blood transfusion; (2) a positive relative response in mixed leucocyte culture indicating sensitization of patient against donor; (3) a low number of marrow cells used for transplantation; (4) marrow grafts from male donors; and (5) lack of infusion of viable donor buffy coat cells in addition to the marrow for transfused patients. The findings confirm the importance of transplanting early before transfusion and indicate that the greatest possible amount of donor marrow (supplemented by stem cells/lymphoid cells derived from the peripheral blood) should be obtained.

Anemia, Aplastic↗
PubMed1983

Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings.

One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.

Adolescent↗
PubMed1983

Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?

The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One-hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment.

Anemia, Aplastic↗
PubMed1983

Relationship of cigarette smoking and radiation exposure to cancer mortality in Hiroshima and Nagasaki.

Cancer mortality among 40,498 Hiroshima and Nagasaki residents was examined in relation to cigarette smoking habits and estimated atomic bomb radiation exposure level. Relative risk (RR) models that are either multiplicative or additive in the two exposures were emphasized. Most analyses were directed toward all nonhematologic (ANH) cancer, stomach cancer, lung cancer, or digestive tract cancer other than stomach cancer, for which there were, respectively, 1,725, 658, 281, and 338 deaths in the follow-up period for this study. Persons heavily exposed to both cigarette smoke and radiation were found to have significantly lower cancer mortality than multiplicative RR models would suggest for ANH cancer, stomach cancer, and digestive tract cancer other than stomach cancer. Surprisingly, the RR function appeared not only to be submultiplicative for some of these cancer site categories but also may be subadditive. The lung cancer RR function could not be distinguished from either a multiplicative or an additive form. The number of deaths was sufficient to permit some more detailed study of ANH cancer mortality: RR functions appeared to be consistent between males and females, though a paucity of heavy smoking females limits the precision of this comparison. The submultiplicative nature of the RR function mentioned above was particularly pronounced among persons who were relatively young (less than or equal to 30 yr of age) at the time of radiation exposure. The RR function for these younger subjects depends strongly on both radiation and cigarette smoke exposure levels. Even light smoking (approximately 5 cigarettes/day) for an extended period of time was associated with a large estimated RR. Implications of these findings are discussed in relation to human carcinogenesis models. As a byproduct, cancer mortality of several sites is significantly related to radiation exposure in this population, after accommodation for the possible confounding effects of cigarette smoking.

Adult↗