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Biomedical subjects

R L Prentice

Publications and source records attributed to R L Prentice.

At least 19 recordsLinked to original sources
PubMed1992

Anti-ganglioside antibodies in peripheral neuropathy.

There have recently been reports that patients with motor neuropathy with multifocal conduction block have high circulating levels of antibodies to the ganglioside GM1. Other reports have described the presence of these antibodies in patients with inflammatory demyelinating neuropathy and patients with lower motor neurone forms of motor neurone disease. We have established an ELISA assay for IgG and IgM antibodies to asialo-GM1 (Sigma). We used this assay to measure such antibodies in serum from normal subjects and from patients with various neurological conditions. In normal subjects, antibodies to asialo-GM1 were present only in low levels. An arbitrary scale with an upper limit of normal was established. Initial studies have found that abnormally high levels of IgG antibodies to asialo-GM1 were present in 4 of 9 patients with inflammatory demyelinating neuropathies (Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy). We found one patient with a monoclonal IgM circulating paraprotein and a motor neuropathy who had a high titre of antibody to asialo-GM1. As yet we have found no patients with motor neurone disease with antibodies to asialo-GM1.

Antibodies↗
PubMed1992

On the use of historical control data to estimate dose response trends in quantal bioassay.

New tests for trend in proportions, in the presence of historical control data, are proposed. One such test is a simple score statistic based on a binomial likelihood for the "current" study and beta-binomial likelihoods for each historical control series. A closely related trend statistic based on estimating equations is also proposed. Trend statistics that allow overdispersed proportions in the current study are also developed, including a version of Tarone's (1982, Biometrics 38, 215-220) test that acknowledges sampling variation in the beta distribution parameters, and a trend statistic based on estimating equations. Each such trend test is evaluated with respect to size and power under both binomial and beta-binomial sampling conditions for the current study, and illustrations are provided.

Analysis of Variance↗
PubMed1991

Epidemiologic data on exogenous hormones and hepatocellular carcinoma and selected other cancers.

Epidemiologic data on the use of oral contraceptives and estrogen replacement therapy in relation to cancers of the endometrium, breast, and ovary are briefly reviewed. This is followed by a more detailed review of the epidemiologic literature on hepatic adenomas and primary hepatocellular carcinoma. There is evidence that combined oral contraceptive use increases the risk of hepatocellular carcinoma in developed countries in which rates for this disease are extremely low. Any such elevation is, however, as yet undetectable in countries where hepatitis B virus is endemic and liver cancer rates are high.

Carcinoma, Hepatocellular↗
PubMed1991

Aspects of the science of cancer prevention trials: lessons from the conduct and planning of clinical trials of a low-fat diet intervention among women.

Cancer prevention trials are contrasted with cancer therapy trials, cardiovascular disease prevention trials, epidemiologic cohort and case-control studies, and trials with surrogate endpoints, in order to highlight some of their unique features and in order to examine the role of such trials in the cancer prevention agenda. The implication of these features and this role are discussed with respect to trial rationale, trial design, and trial protocol, with planning exercises for proposed dietary fat intervention trials among women providing illustration. Finally, some considerations are mentioned for the planning of a primary prevention trial of breast cancer using tamoxifen.

Aged↗
PubMed1991

Quantitative review of studies of dietary fat and rat colon carcinoma.

A quantitative overview of 14 studies of rat colon carcinogenesis was undertaken to examine the relationship between fat intake, and fat intake by degree of saturation, on the incidence of colon carcinoma while controlling for calorie consumption. Calorie consumption was not recorded in 11 of the 14 studies. Hence, two types of analyses were conducted. The first examines carcinoma incidence as a function of percent fat (by weight), with calories controlled for by including weight gain per week in the analysis. The second estimates calories per day, for studies not providing such information, using weight gain per week and age at death, followed by a joint analysis of estimated fat calories and estimated total calories. With either approach, a rather strong positive relationship between colon carcinoma incidence and fat intake is indicated for Fischer 344 rats, but no association is apparent for Sprague-Dawley rats. This situation is somewhat clarified when the degree of saturation is taken into account: both strains gave results that suggest a negative relationship between colon cancer incidence and omega-3 fatty acids intake and a positive relationship with non-omega-3 polyunsaturated fat intake among Fischer 344 rats. These analyses suggest an important and specific role for dietary fat in the promotion of rat colon carcinoma.

Animals↗
PubMed1991

Estimating equations for parameters in means and covariances of multivariate discrete and continuous responses.

Generalized estimating equations are introduced in an ad hoc fashion for the covariance matrix of a multivariate response. These equations are to be solved jointly with score equations from a generalized linear model for mean parameters. A class of quadratic exponential models is used to develop joint estimating equations for mean and covariance parameters in a more systematic fashion, and proposals for the use of such equations are developed. Comments on the relative merits of the ad hoc and model-based approaches to estimation are given and a regression illustration with a bivariate response is provided.

Anticonvulsants↗
PubMed1991

Nonparametric tests of association between survival time and continuously measured covariates: the logit-rank and associated procedures.

O'Brien's logit-rank procedure (1978, Biometrics 34, 243-250) is shown to arise as a score test based on the partial likelihood for a proportional hazards model provided the covariate structure is suitably defined. Within this framework the asymptotic properties claimed by O'Brien can be readily deduced and can be seen to be valid under a more general model of censoring than that considered in his paper. More important, perhaps, it is now possible to make a more natural and interpretable generalization to the multiple regression problem than that suggested by O'Brien as a means of accounting for the effects of nuisance covariates. This can be achieved either by modelling or stratification. The proportional hazards framework is also helpful in that it enables us to recognize the logit-rank procedure as being one member of a class of contending procedures. One consequence of this is that the relative efficiencies of any two procedures can be readily evaluated using the results of Lagakos (1988, Biometrika 75, 156-160). Our own evaluations suggest that, for non-time-dependent covariates, a simplification of the logit-rank procedure, leading to considerable reduction in computational complexity, is to be preferred to the procedure originally outlined by O'Brien.

Biometry↗
PubMed1990

Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption.

International variations and national time trends in disease rates suggest major associations between dietary fat and several important cancers. In contrast, case-control and cohort studies of dietary fat in relation to the same cancers generally report weak associations, or have failed to detect any association with fat intake. This study was undertaken in an attempt to understand the apparent discrepancy between these observations. The results provide an insight into the magnitude of cancer risk reduction that may follow from a practical reduction in dietary fat. Regression analyses of international variations in cancer incidence rates were used to estimate relative risks (RR) as a function of fat intakes for both males and females. These analyses focused on cancers of the breast, colon, rectum, ovary, and endometrium in females, and colon, rectum, and prostate cancers in males. Ages 55-69 and 30-44 were considered in order to compare RR estimates between an older and younger age group, and between post- and pre-menopausal women. Corresponding RR estimates were also calculated, based on the regression of changes in disease rates from the mid-1960s to 1980 on changes in dietary fat, using data from several countries. A strong degree of consistency with the RR estimates from international comparisons was observed. The international regression analyses were also used to project changes in cancer rates among Japanese migrants to the United States. A high level of consistency with the observed disease-rate changes was noted. Similarly, the international data analyses were used to project RRs for the fat intake categories used in specific case-control and cohort studies, while acknowledging measurement error in individual dietary assessment. Although certain exceptions are noted, considerable consistency was found between the aggregate and analytic data results, leaving open the strong possibility that a practical reduction in dietary fat could result in a major reduction in the incidence of several prominent cancers in the United States and in other nations having high fat consumption.

Adult↗
PubMed1990

Results of a randomized feasibility study of a low-fat diet.

A 2-year randomized clinical trial was conducted to test whether free-living women aged 45 to 69 years can reduce the fat content of their diet from the typical US level of approximately 39% to 20% of energy from fat, using readily available foods, when given nutritional and behavioral counseling and social support. Three clinical units randomized 303 selected volunteers into intervention (low-fat eating plan) or control (customary diet) groups. The two groups were comparable at baseline. The intervention group received nutrition instruction and behavioral counseling largely in permanent groups of 12 to 15 participants meeting weekly, then biweekly, and finally monthly. At 6 months, they had substantially reduced the mean proportion of total energy from fat from 39.1% to 20.9%, compared with the control group's nonsignificant reduction from 39.0% to 38.1%. At 12 and 24 months, they sustained the reduction of energy from fat. Weight loss and plasma cholesterol level changes in the intervention group supported the self-recorded dietary intake changes. Attendance at intervention sessions averaged 75% during the first 6 months and, subsequently, 60% to 70%. Four-day food records for the randomized women were obtained at 6 and 12 months from approximately 95% and at 24 months from 87%. A clinical trial of a low-fat diet is feasible in women.

Aged↗
PubMed1989

Cell death by apoptosis in acute leukaemia.

We have previously demonstrated that when freshly isolated childhood T-cell acute lymphoblastic leukaemia cells are incubated in growth medium after isolation from blood, chromatin is rapidly cleaved into nucleosomal sized fragments that are multiples of 200 bp. The fragmentation is similar to that observed in other types of cells undergoing apoptosis or programmed cell death. In this study we describe a more comprehensive approach to the study of DNA fragmentation in leukaemia. Fragmentation was observed in freshly isolated cells from patients with T-cell acute lymphoblastic leukaemia and in one with common acute lymphoblastic leukaemia. Frozen samples of T-cell acute lymphoblastic leukaemia, common acute lymphoblastic leukaemia, and acute myeloid leukaemia cells also showed fragmentation of DNA. However, no fragmentation was evident in normal leukocytes treated under the same conditions. Ultrastructural studies on the isolated leukaemia cells demonstrate that the chromatin cleavage observed biochemically is associated with morphological changes characteristic of apoptosis.

Cell Survival↗
PubMed1989

Surrogate endpoints in clinical trials: definition and operational criteria.

I discuss the idea of using surrogate endpoints in the context of clinical trials to compare two or more treatments or interventions in respect to some 'true' endpoint, typically a disease occurrence. In order that treatment comparison based on a surrogate response variable have a meaningful implication for the corresponding true endpoint treatment comparison, a rather restrictive criterion is proposed for use of the adjective 'surrogate'. Specifically, I propose that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response. This criterion essentially requires the surrogate variable to 'capture' any relationship between the treatment and the true endpoint, a notion that can be operationalized by requiring the true endpoint rate at any follow-up time to be independent of treatment, given the preceding history of the surrogate variable. I then discuss this operational criterion in the examples of the accompanying papers and in the setting of trials aimed at the primary and secondary prevention of cancer.

Breast Neoplasms↗
PubMed1989

Further results on covariate measurement errors in cohort studies with time to response data.

The impact of covariate measurement errors on the estimation of relative risk regression parameters is discussed. First the dependence of the induced relative risk process on the cumulative baseline failure rate function is noted. Next induced relative risk models under some specific failure time and measurement error models are described, including the much simplified models that are appropriate under a 'rare disease' assumption. The presentation then turns to the joint estimation of relative risk parameters of primary interest along with measurement error parameters. A partial likelihood product is proposed for such estimation and asymptotic properties are indicated. Guidance is also presented as to the appropriate size of a 'validation' sample relative to the full cohort size. Finally some more general considerations are presented as to the usefulness and interpretation of deattenuated regression coefficients.

Analysis of Variance↗
PubMed1989

Validity of international, time trend, and migrant studies of dietary factors and disease risk.

A linear form relative risk model is used to identify circumstances in which various types of aggregate data lead to valid inferences on relative risk parameters. Upon making a random effects assumption, international or time trend data can lead to appropriate relative risk parameter estimation using iteratively reweighted least-squares procedures. Adequate confounding factor control, however, will typically require data on the distribution of confounding factors in each country or time period. For a simple interpretation of relative risk parameters one may also require data on the joint distribution of primary and confounding factors in each country or time period. Hence disease rate data need to be supplemented by dietary and risk factor survey data in order to avoid confounding bias. Measurement error in individual dietary assessment may, however, limit the ability to quantify the dependence of relative risk on dietary factors, unless the relative risk function is approximately linear in the dietary factors of interest. Most studies of migrant populations involve a comparison of migrant mortality rates with those of their countries of emigration and immigration, with little or no data collection on the dietary habits and risk factors of the migrants themselves. The potential of more comprehensive aggregate data and analytic migrant studies in the diet and disease area is briefly indicated. These issues and methods are illustrated using various types of data pertinent to the association between dietary fat and breast cancer.

Breast Neoplasms↗
PubMed1989

Spontaneous programmed death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro.

When B-chronic lymphocytic leukaemia (B-CLL) cells derived from peripheral blood were cultured in vitro, a substantial proportion of them spontaneously died by apoptosis. This type of cell death is morphologically and biochemically distinct from necrosis and has previously been found to occur under physiologic and certain pathologic conditions where cell deletion appears controlled and biologically meaningful. By 30 h of culture, approximately 20% of the unfractionated B-CLL cells were affected. There was no significant difference in the incidence of apoptosis in T-cell depleted and undepleted cultures or when either autologous or normal human serum was used. Furthermore, seeding densities of 2 x 10(6) and 5 x 10(5) cells/ml resulted in a similar incidence of apoptosis, indicating that cell density was unlikely to be a contributing factor in producing the death. The finding that B-CLL cells spontaneously die in vitro has at least two important implications. Firstly, previous work relating to some of the functions of B-CLL cells and their interactions with T cells may require re-evaluation. Secondly, an understanding of the mechanisms involved in the induction of apoptosis in this disease may have therapeutic consequences.

Blood Cell Count↗