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Biomedical subjects

R L Prentice

Publications and source records attributed to R L Prentice.

At least 37 records · Page 2Linked to original sources

Designs for synthetic case-control studies in open cohorts.

Several designs are proposed for case-control studies within cohorts when the cohort is open to late entry. These and previously proposed designs are examined with respect to consistency and efficiency of relative risk parameter estimation, and a small simulation study is reported. If study costs increase in proportion to the total number of "at-risk" controls, the most efficient design, Design C, is as follows. For a case failing at time t, controls are selected at random (and without regard to "at-risk" status) from among cohort members who are (i) known not to have failed prior to t and (ii) have not been previously selected as controls. At each t, control sampling proceeds until a prespecified number of controls who are "at risk" at t have been obtained. The efficiency advantage of Design C over that of the standard case-control design proposed by Thomas (in Appendix to Liddell, McDonald, and Thomas, 1977, Journal of the Royal Statistical Society, Series B 140, 469-490) will often be small. If, on the other hand, the costs increase in proportion to the number of distinct "at-risk" controls, Design C is no longer the most efficient design. In this case, several alternative designs are proposed.

Biometry

Comparison of three-day butoconazole treatment with seven-day miconazole treatment for vulvovaginal candidiasis.

In this multicenter, parallel, randomized, investigator-blind trial, we compared the safety and efficacy of a three-day regimen of 2% butoconazole vaginal cream with those of a seven-day regimen of 2% miconazole vaginal cream. Enrolled were 271 nonpregnant women with vulvovaginal candidiasis. Each patient administered her assigned study medication to the posterior vaginal fornix for three or seven consecutive nights. All 271 patients were included in the safety evaluation, and 225 (111 receiving butoconazole and 114 receiving miconazole) were included in the efficacy evaluation. Eight to ten days after treatment completion, 88% of the butoconazole-treated patients and 91% of the miconazole-treated patients were Candida negative; 80% of the butoconazole-treated patients and 82% of the miconazole-treated patients were considered clinically cured. Thirty days after treatment completion, 73% of the butoconazole-treated patients and 69% of the miconazole-treated patients remained Candida negative; 78% of the butoconazole-treated patients and 80% of the miconazole-treated patients remained free of clinical symptoms of vulvovaginitis. None of the differences between the two treatment groups was statistically significant. Six patients (four receiving butoconazole and two receiving miconazole) reported increased symptoms of vulvovaginal irritation, and three of them (two receiving butoconazole and one receiving miconazole) withdrew from the trial. Thus, the efficacy and safety of the three-day butoconazole treatment regimen were equivalent to those of the seven-day miconazole treatment regimen. The advantage of the shorter butoconazole treatment is increased patient compliance with maintenance of high efficacy.

Administration, Intravaginal

Aspects of the rationale for the Women's Health Trial.

A 5.5-fold range in breast cancer incidence rates in 21 countries shows strong correlation with national estimates of per capita intake of dietary fat, but not with other caloric sources (proteins and carbohydrates). It is argued that certain breast cancer and hormone factors may contribute little to the explanation of such international variations in incidence of this neoplasm. It is further argued that experimental studies in animals support a specific role for dietary fat in the promotion of mammary tumors, but the effects of calories alone seem to be largely restricted to tumor initiation. Finally, data from international, migrant-population, and analytic epidemiologic investigations are used to motivate the basic relative risk assumption of study designs thus far proposed for the Women's Health Trial, and some continuing motivations for a dietary intervention (low-fat diet) trial are discussed.

Aged

Correlated binary regression with covariates specific to each binary observation.

Regression methods are considered for the analysis of correlated binary data when each binary observation may have its own covariates. It is argued that binary response models that condition on some or all binary responses in a given "block" are useful for studying certain types of dependencies, but not for the estimation of marginal response probabilities or pairwise correlations. Fully parametric approaches to these latter problems appear to be unduly complicated except in such special cases as the analysis of paired binary data. Hence, a generalized estimating equation approach is advocated for inference on response probabilities and correlations. Illustrations involving both small and large block sizes are provided.

Adolescent

DNA fragmentation in childhood T-cell acute lymphoblastic leukaemia.

DNA isolated from 12 patients with childhood acute lymphoblastic leukaemia (T-ALL), analysed by gel electrophoresis exhibited a degradation pattern of increasing nucleosome repeat size, similar to that observed when nuclei from normal control cells are incubated with micrococcal nuclease. None of a group of adult T-ALL showed this fragmentation, nor was the pattern observed in normal control T-cells, cells from patients with a number of other forms of leukaemia, or in B-lymphoblastoid cells under the same incubation conditions. This phenomenon appears to be related to the changes in DNA that occur in glucocorticoid-induced cell death in mouse thymocytes, radiation-damaged spleen cells, and in cytotoxic T-cells deprived of interleukin 2. The method described here promises to be a reliable, simple approach to the characterization of T-ALL in childhood and may aid in the clinical management of this form of leukaemia.

Adolescent

Potentiation of hybridoma production by the use of mouse fibroblast conditioned media.

L-CM is a conditioned medium prepared from cultures of L-929 cells, a murine fibroblast line. It will promote the growth and antibody secretion of B cell hybridomas after fusion as well as facilitating cloning at limit dilution and the growth of cloned B cell lines in bulk culture. The medium is easy to prepare and stores well at 4 degrees C. It thus provides a convenient alternative to the use of feeder cells in the production of monoclonal antibodies.

Animals

Biostatistical issues and concepts in epidemiologic research.

This paper describes recent developments in failure time regression, and the application of such methods to epidemiologic data. Relative risk and odds ratio estimation procedures are described under cohort and case-control sampling, and under some less standard designs for sampling within a cohort. Some special issues that arise in the analysis of vital data are also mentioned. While methods for descriptive analyses are emphasized some attention is also given to mechanistic models for carcinogenesis and their uses. Topics meriting further methodologic development are delineated throughout.

Epidemiology

Rearrangements of T-cell receptor beta-chain genes in human leukaemias.

Rearrangements of the T-cell receptor (TCR), beta-chain genes and immunoglobulin (Ig) heavy chain genes in several T-cell leukaemias (T-ALL and ATL), and some B-cell and myelogenous leukaemias were investigated. Two out of 15 cases of T-cell leukaemia tested failed to show a rearrangement pattern of TCR beta genes although both expressed mRNA for this gene. The remaining 13 cases showed diverse patterns of rearrangements involving either C beta 1, C beta 2 or both. C beta 1 but not C beta 2 was deleted in some of the T-cell leukaemias. Polyclonal T cells from four normal individuals showed the germ line pattern and an additional two bands in Hind III digested DNA. Except for one, all cases of C-ALL (B-cell leukaemia) showed a rearranged JH locus which was not evident in any of T-cell leukaemias studied. One case of B-cell leukaemia showed a rearrangement of both TCR beta genes and JH genes. The results of these studies suggest that rearrangement of TCR and Ig genes occurs at a very early stage of differentiation of stem cells and does not appear to play a direct role in leukaemogenesis per se.

Antigens, Neoplasm

On the application of linear relative risk regression models.

Motivations for considering linear relative risk models are described. These include covariate data reduction and the testing of additivity of covariate effects on the relative risk. A simulation study was conducted in order to study properties of asymptotic distributional approximations and iterative convergence properties. Parameter transformations and likelihood ratio approximations are considered for confidence interval calculation.

Analysis of Variance

On the design of synthetic case-control studies.

A design is proposed for "case-control within cohort" studies. In this design, controls are sampled without replacement from failure-free members of the cohort at each distinct failure time. Upon selection, a subject ceases to be eligible for control selection at later failure times. Also, if a subject failing at time t had been selected as a control at t' less than t, then the matched controls at t are selected to have also been at risk at t'. In these circumstances correlation exists between score statistic contributions at t and t'. An estimator is developed for this correlation. A small simulation study compares the design just described to other possible synthetic case-control designs.

Biometry

Purification of two allergens from Dermatophagoides pteronyssinus using monoclonal antibodies.

Fractionation of soluble extracts from the house dust mite Dermatophagoides pteronyssinus (DP) by SDS-PAGE and crossed immunoelectrophoresis (CIE) revealed at least fifty distinct protein components. Western blotting and crossed radioimmunoelectrophoresis (CRIE) indicated that fewer than one quarter of these components were allergens as determined by their ability to bind IgE from allergic individuals. Following immunization with a crude extract, two monoclonal antibodies were raised against distinct components which exhibited IgE binding capacities in Western blot and CRIE. Affinity chromatography using these monoclonal antibodies yielded components which elicited positive skin test reactions in patients allergic to DP.

Allergens

Central nervous system echovirus infection in Bruton's X-linked hypogammaglobulinemia.

A patient with Bruton's X-linked hypogammaglobulinemia, who developed the typical syndrome associated with systemic echovirus 3 infection whilst on routine intramuscular gammaglobulin replacement therapy, is described. Following regular infusions of specific antibody-containing plasma from his spouse, he has shown sustained clinical improvement over a period of two years, and is, therefore, one of the very rare cases with this syndrome to survive for more than a few months.

Adolescent

Relative risk regression analysis of epidemiologic data.

Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation procedures with moderate numbers of disease events.

Age Factors