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D B Rubin

Publications and source records attributed to D B Rubin.

9 recordsLinked to original sources
PubMed1992

The effect of sulfasalazine on bovine endothelial cell proliferation and cell cycle phase distribution. Comparison with olsalazine, 5-aminosalicylic acid, and sulfapyridine.

Sulfasalazine is used in the treatment of chronic inflammatory states, for example, in inflammatory bowel disease and to a lesser degree in rheumatoid arthritis. In chronic inflammation, the formation of new blood vessels may play a key role in maintaining the inflammatory state. This process is dependent on the activation and proliferation of the endothelial cells. To investigate the possible role of sulfasalazine and its metabolites, sulfapyridine and 5-aminosalicylic acid, we examined the effect of these drugs on vascular endothelial cell proliferation in vitro. Cultures of bovine aortic endothelial cells were incubated with sulfasalazine and its metabolites. At 24 hours of incubation, sulfasalazine inhibited tritiated thymidine incorporation and cell proliferation and had already slowed S-phase progression at a concentration greater than 0.125 mmol/L. After 3 hours of incubation, sulfasalazine inhibition of tritiated thymidine incorporation into the DNA of endothelial cells was observed. This inhibition was completely reversible 24 hours after the drug was removed. One of the possible mechanisms for the inhibition of endothelial cell proliferation is interference with the de novo synthesis of thymidine that depends on folate-dependent enzymes. The effect of deoxyuridine and tetrahydrofolate on tritiated thymidine incorporation into cellular DNA, as well as release of tritium to water by [5-3H]-labeled deoxyuridine on methylation to thymidine, were used as probes for the de novo synthesis of thymidine. Deoxyuridine and tetrahydrofolate, when added to cells either individually or together for 3 hours, suppressed incorporation of tritiated thymidine into DNA through an increase in de novo thymidine synthesis. Sulfasalazine, but not its metabolites, reduced this suppression.2+ culture is inhibited by sulfasalazine and olsalazine but not by their metabolites. This inhibition appears to depend partly on the reduction of de novo synthesis of thymidine that is folate dependent.

Aminosalicylic Acids↗
PubMed1991

Multiple imputation in health-care databases: an overview and some applications.

Multiple imputation for non-response replaces each missing value by two or more plausible values. The values can be chosen to represent both uncertainty about the reasons for non-response and uncertainty about which values to impute assuming the reasons for non-response are known. This paper provides an overview of methods for creating and analysing multiply-imputed data sets, and illustrates the dramatic improvements possible when using multiple rather than single imputation. A major application of multiple imputation to public-use files from the 1970 census is discussed, and several exploratory studies related to health care that have used multiple imputation are described.

Databases, Factual↗
PubMed1991

Practical implications of modes of statistical inference for causal effects and the critical role of the assignment mechanism.

Causal inference in an important topic and one that is now attracting serious attention of statisticians. Although there exist recent discussions concerning the general definition of causal effects and a substantial literature on specific techniques for the analysis of data in randomized and nonrandomized studies, there has been relatively little discussion of modes of statistical inference for causal effects. This presentation briefly describes and contrasts four basic modes of statistical inference for causal effects, emphasizes the common underlying causal framework with a posited assignment mechanism, and describes practical implications in the context of an example involving the effects of switching from a name-band to a generic drug. A fundamental conclusion is that in such nonrandomized studies, sensitivity of inference to the assignment mechanism is the dominant issue, and it cannot be avoided by changing modes of inference, for instance, by changing from randomization-based to Bayesian methods.

Bayes Theorem↗
PubMed1991

The influence of exogenous eicosanoids on the radiation response of cultured bovine aortic endothelial cells.

The radioprotection by several eicosanoids was investigated in cultures of bovine aortic endothelial cells. One hour before irradiation (0-500 cGy, 137Cs gamma rays) 10 micrograms/ml of PGD2, PGE1, PGI2, misoprostol (PGE1-analog), 16,16-dimethyl PGE2, PGA2, or 1 microgram/ml LTC4 was added. Radiation decreased incorporation of [3H]thymidine at 4 h, cell number/culture at 24 h, and cell survival as measured by colony formation. Under these conditions the eicosanoids were not radioprotective. Two eicosanoids, PGD2 and PGA2, appeared to be toxic. Because receptors might mediate eicosanoid-induced radioprotection, radioligand binding of PGE2 and LTC4 and levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured. Evidence for a receptor was equivocal; there was nonspecific binding and metabolism of LTC4. The level of cAMP was elevated by 16-16-dimethyl-PGE2 in the presence of isobutyl methylxanthine; however, this combination of the prostaglandin and the methylxanthine was not radioprotective. These investigations suggest that an elevated cAMP level alone does not lead to eicosanoid-induced radioprotection of bovine aortic endothelial cell monolayers in vitro.

16,16-Dimethylprostaglandin E2↗
PubMed1990

Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome.

In this prospective study of 45 patients, we tested the hypothesis that markedly elevated levels of plasma von Willebrand antigen (vWf-Ag) a marker of endothelial cell injury, might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome. Acute lung injury was quantified on a four-point scoring system. At the time of entry into the study, none of the 45 patients had evidence of lung injury. Subsequently, 15 patients developed lung injury and 30 patients did not develop lung injury. The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury (588 +/- 204 vs. 338 +/- 196, percentage of control, P less than 0.01). Furthermore, a plasma vWf-Ag level greater than or equal to 450 was 87% sensitive and 77% specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis. In addition, the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80% for acute lung injury. Also, a plasma vWf-Ag level greater than 450 had a positive predictive value of 80% for identifying nonsurvivors. Thus, in patients with nonpulmonary sepsis, an elevated level of plasma vWf-Ag is a useful, early biochemical marker of endothelial injury and it has both predictive and prognostic value.

Acute Disease↗
PubMedDate not supplied

Computational aspects of analysing random effects/longitudinal models.

Random effects and longitudinal models are becoming increasingly popular in the analysis of many types of data, including medical and biopharmaceutical, because of their richness and flexibility. They can be, however, difficult to fit using traditional statistical tools. Fortunately, there now exists a burgeoning collection of newer computational methods that can be applied to draw inferences with such models. This review attempts to provide an introduction to some of these techniques by describing them as extensions of the EM algorithm, currently a standard tool for the analysis of longitudinal and random effects models. For clarity of exposition, the extensions are classified into three types: large-sample iterative; large-sample simulation, and small-sample simulation.

Longitudinal Studies↗