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D B Rubin

Publications and source records attributed to D B Rubin.

At least 37 records · Page 2Linked to original sources
PubMed1996

WR-1065 and radioprotection of vascular endothelial cells. II. Morphology.

Although the aminothiol WR-1065 protects normal tissues, its direct effect on the damage and restoration of the vascular endothelium is not clear. In endothelial cells, WR-1065 attenuates both the DNA damage and the G1-phase arrest induced by radiation. After the destruction of nearby endothelial cells, the survivors rearrange their cytoskeleton, migrate and replicate. To determine the effect of radiation on morphology and migration, portions of bovine aortic endothelial cell cultures were denuded with a pipette tip and irradiated (137Cs gamma rays). The following observations were noted after 5 Gy: within 10 min, there was increased formation of protein-mixed disulfides including actin-mixed disulfide; after 30-min, alpha 5 beta 1, the integrin receptor for fibronectin, was up-regulated on the apical membrane surface. Within 5 h, actin-containing stress fibers reorganized, although there was no change in the total filamentous (F-)actin content within the cells. Compared to controls after 24 h, the irradiated cells had migrated 15% farther (P < 0.01), and at the leading edge covered twice the surface area (P < 0.0001). The addition of 2 mM WR-1065 for 2 h before 5 Gy inhibited the increased expression of alpha 5 beta 1, promoted retention of stress fibers and prevented the enhanced cell migration and spreading. These results indicate that WR-1065 prevents radiation-induced morphological responses. This effect appears to be mediated by an impact on both adhesion molecule expression and cytoskeletal reorganization.

Actin Cytoskeleton↗
PubMed1996

Matching using estimated propensity scores: relating theory to practice.

Matched sampling is a standard technique in the evaluation of treatments in observational studies. Matching on estimated propensity scores comprises an important class of procedures when there are numerous matching variables. Recent theoretical work (Rubin, D. B. and Thomas, N., 1992, The Annals of Statistics 20, 1079-1093) on affinely invariant matching methods with ellipsoidal distributions provides a general framework for evaluating the operating characteristics of such methods. Moreover, Rubin and Thomas (1992, Biometrika 79, 797-809) uses this framework to derive several analytic approximations under normality for the distribution of the first two moments of the matching variables in samples obtained by matching on estimated linear propensity scores. Here we provide a bridge between these theoretical approximations and actual practice. First, we complete and refine the nomal-based analytic approximations, thereby making it possible to apply these results to practice. Second, we perform Monte Carlo evaluations of the analytic results under normal and nonnormal ellipsoidal distributions, which confirm the accuracy of the analytic approximations, and demonstrate the predictable ways in which the approximations deviate from simulation results when normal assumptions are violated within the ellipsoidal family. Third, we apply the analytic approximations to real data with clearly nonellipsoidal distributions, and show that the theoretical expressions, although derived under artificial distributional conditions, produce useful guidance for practice. Our results delineate the wide range of settings in which matching on estimated linear propensity scores performs well, thereby providing useful information for the design of matching studies. When matching with a particular data set, our theoretical approximations provide benchmarks for expected performance under favorable conditions, thereby identifying matching variables requiring special treatment. After matching is complete and data analysis is at hand, our results provide the variances required to compute valid standard errors for common estimators.

Analysis of Variance↗
PubMed1995

In utero exposure to phenobarbital and intelligence deficits in adult men.

OBJECTIVE: To test whether exposure to phenobarbital in utero is associated with deficits in intelligence scores in adult men and whether the magnitude of the postnatal effect is mediated by exposure parameters and/or postnatal environmental factors. DESIGN: Two double-blind studies were conducted on independent samples of adult men prenatally exposed to phenobarbital and matched control samples using different measures of general intelligence. Based on data from control subjects, regression models were built relating intelligence scores to relevant pre-exposure matching variables and age at testing. Models generated predicted scores for each exposed subject. Group mean differences between the individually predicted and observed scores estimated exposure effects. SETTING: Copenhagen, Denmark. PARTICIPANTS: Exposed subjects were adult men born at the largest hospital in Copenhagen between 1959 and 1961 who were exposed to phenobarbital during gestation via maternal medical treatment and whose mothers had no history of a central nervous system disorder and no treatment during pregnancy with any other psychopharmacological drug. Study 1 included 33 men and study 2, 81 men. Controls were unexposed members of the same birth cohort matched on a wide spectrum of maternal variables recorded prenatally and perinatally. Controls for studies 1 and 2 included 52 and 101 men, respectively. MAIN OUTCOME MEASURES: In study 1: Wechsler Adult Intelligence Scale (Danish version); in study 2: Danish Military Draft Board Intelligence Test (Børge Priens Prøve). RESULT: Men exposed prenatally to phenobarbital had significantly lower verbal intelligence scores (approximately 0.5 SD) than predicted. Lower socioeconomic status and being the offspring of an "unwanted" pregnancy increased the magnitude of the negative effects. Exposure that included the last trimester was the most detrimental. CONCLUSION: Phenobarbital exposure during early development can have long-term deleterious effects on cognitive performance. Detrimental environmental conditions can interact with prenatal biological insult to magnify negative outcomes. Physicians are urged to use increased caution in prescribing such medications during pregnancy.

Adult↗
PubMed1995

The analysis of repeated-measures data on schizophrenic reaction times using mixture models.

Reaction times for schizophrenic individuals in a simple visual tracking experiment can be substantially more variable than for non-schizophrenic individuals. Current psychological theory suggests that at least some of this extra variability arises from an attentional lapse that delays some, but not all, of each schizophrenic's reaction times. Based on this theory, we pursue models in which measurements from non-schizophrenics arise from a normal linear model with a separate mean for each individual, whereas measurements from schizophrenics arise from a mixture of (i) a component analogous to the distribution of response times for non-schizophrenics and (ii) a mean-shifted component. We fit four mixture models within this framework, where the distinctions between models arise from assumptions about the variance of the shifted observations and the exchangeability of schizophrenic individuals. Some of these models can be fit by maximum likelihood using the EM algorithm, and all can be fit using the ECM algorithm, where the covariance matrices associated with the parameters are calculated by the SEM and SECM algorithms, respectively. Bayesian model monitoring using posterior predictive checks is invoked to discard models that fail to reproduce certain observed features of the data and to stimulate the development of better models.

Algorithms↗
PubMed1995

Bismuth subsalicylate toxicity as a cause of prolonged encephalopathy with myoclonus.

Bismuth subsalicylate preparations are over-the-counter products for gastrointestinal complaints. Bismuth toxicity causes delirium, psychosis, ataxia, myoclonus, and seizures and is reversible over several weeks or months, when bismuth intake is stopped. We report a 54-year-old man with a 6-week history of progressive confusion and memory difficulty and a 2-3-week history of involuntary movements and gait impairment. His encephalopathy was further characterized by marked multifocal myoclonic jerks, coarse postural tremors, postural instability, and gait ataxia. He gradually improved. Extensive toxic, metabolic, and infectious workup demonstrated bismuth toxicity. Spinal tap and brain magnetic resonance scan were normal. Electroencephalography showed bihemispheric slowing. As his encephalopathy cleared, he reported using bismuth subsalicylate long term (daily intake of 8 oz). Bismuth levels 5 weeks after cessation of bismuth were elevated and normalized after 12 weeks. He followed a typical course for bismuth toxicity with subacute progressive encephalopathy and gradual recovery. Creutzfeldt-Jakob was strongly considered due to his rapidly progressive encephalopathy, multifocal myoclonus, and ataxia. Due to its rarity, bismuth toxicity is often overlooked. We hope this presentation will increase recognition of bismuth toxicity. We believe more detailed labeling of bismuth products is needed to avoid similar toxicity from this readily available product.

Bismuth↗
PubMed1995

Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer.

OBJECTIVE: The authors' objective was to quantitatively assess angiogenesis or neovascularity within node-negative colon cancers and to determine if increased angiogenesis correlated with higher recurrence and lower survival rates. SUMMARY BACKGROUND DATA: Neovascularization promotes rapid tumor growth by facilitating nutrient and metabolite exchange. Recent work with breast and nonsmall cell lung cancers has shown that low angiogenic activity imparts a lower risk of recurrence and metastasis. Although adjuvant therapy is beneficial for patients with node-positive colon cancers, no such benefit has been demonstrated for patients with node-negative lesions. Nevertheless, up to 30% of this latter group will experience recurrence. We sought to identify a subset of patients with node-negative colon cancers at high risk for recurrence who might benefit from such therapy. METHODS: One hundred five node-negative colon cancers were immunostained for endothelial cell factor VIII-related antigen. Blood vessels within three microscopic fields at 100X magnification were counted, the mean calculated, and an angiogenesis score assigned. A subjective angiogenesis grade (1-4) was assigned after each slide was surveyed in its entirety. Score and grade were then assessed with respect to cancer recurrence and patient survival. RESULTS: Mean patient age was 71 years (range, 41-90 years) and mean tumor size, 5.6 cm (range, 2-12 cm). Mean follow-up was 6.5 years; mean angiogenesis score, 27.9 (range, 4-50); and mean grade, 2.0 (range, 1-4). Patients living 5 years had significantly lower angiogenesis scores than did nonsurvivors (22.8 vs. 43.2, p = 0.0004). Each 10-vessel increase in score imparted a 2.0-fold greater hazard of death and a 2.7-fold greater hazard of recurrence. The probability of surviving 5 years is estimated by: [formula: see text] and the probability of recurrence is estimated by: [formula: see text] CONCLUSIONS: Angiogenesis within colon cancer is an important predictor of tumor behavior and may identify patients at higher risk for recurrence and early death.

Adenocarcinoma↗
PubMed1994

Tumor angiogenesis and rectal carcinoma.

PURPOSE: This study was designed to determine whether those rectal cancers that demonstrated increased vessel ingrowth or angiogenesis behave in a different fashion. METHODS: The paraffin blocks of 48 rectal cancers removed by low anterior or abdominoperineal resection were recalled and immunostained with a monoclonal antibody specific for endothelial cell Factor VIII. The intense reddish brown color imparted to blood vessels facilitated their quantification which was undertaken at x100 and x200 magnification. Vessel counts within three microscopic fields were averaged and the relationships between angiogenesis score and tumor size, depth of invasion, incidence of lymph node or distant metastases, and survival were assessed. RESULTS: Significantly higher angiogenesis scores were seen in tumors with transmural penetration (at x100, P = 0.002; at x200, P = 0.002) and in patients dying before five years (at x100, P = 0.013; at x200, P = 0.034). Although higher angiogenesis scores were seen in patients with larger tumors and metastases, these trends were not statistically significant. CONCLUSIONS: Our results suggest that the growth of rectal cancer is dependent on the ingrowth of new blood vessels, and that increased vascularity promotes dissemination and adversely affects survival.

Adenocarcinoma↗
PubMed1993

Tasks in statistical inference for studying variation in medicine.

When studying variation in medicine, traditional hypothesis-testing procedures are too limited to obtain useful inferences except in special situations. More generally, full probability modelling is necessary. Even a relatively simple example can illustrate this point rather dramatically. The development and application of full-probability methods for medical problems comprise exciting areas for statistical and medical researchers, especially if working together.

Health Services Research↗
PubMed1993

Hierarchical logistic regression models for imputation of unresolved enumeration status in undercount estimation.

"In this article we describe a logistic regression modeling approach for nonresponse in the [U.S.] Post-Enumeration Survey (PES) that has desirable theoretical properties and that has performed well in practice.... In the 1990 PES, interviews were not obtained from approximately 1.2% of households in the sample, and approximately 2.1% of the individuals in interviewed households were considered unresolved after follow-up....The missing binary enumeration statuses for these unresolved cases were replaced with probabilities estimated under a statistical model that incorporated covariate information observed for these cases. This article describes an approach to modeling missing binary outcomes when there are a large number of covariates."

Americas↗
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↗