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Biomedical subjects

E Bartfay

Publications and source records attributed to E Bartfay.

15 recordsLinked to original sources
PubMed2006

Comparing the predictive value of neural network models to logistic regression models on the risk of death for small-cell lung cancer patients.

Cancer is one of the leading causes of mortality in the developed world, and prognostic assessment of cancer patients is indispensable in medical care. Medical researchers are accustomed to using regression models to predict patient outcomes. Neural networks have been proposed as an alternative with great potential. Nonetheless, empirical evidence remains lacking to support the application of this technique as the appropriate method to investigate cancer prognosis. Utilizing data on patients from two National Cancer Institute of Canada clinical trials, we compared predictive accuracy of neural network models and logistic regression models on risk of death of limited-stage small-cell lung cancer patients. Our results suggest that neural network and logistic regression models have similar predictive accuracy. The distributions of individual predicted probabilities are very similar. On occasion, however, the prediction pairs are quite different, suggesting that they do not always give the same interpretations of the same variables.

Adult↗
PubMed2001

Statistical inferences for a twin correlation with multinomial outcomes.

Current methods for statistical analysis of twin studies focus on continuous and dichotomous data, while only limited methodology exists for analysing multinomial data. As a consequence, investigators are often tempted to collapse multinomial data into two categories simply to facilitate the analysis. We address this problem by developing and evaluating two approaches to the assessment of twin correlation for an outcome variable having more than two nominal categories. One method developed is an extension of the goodness-of-fit approach, while the other method is based on large sample normal theory. Procedures for confidence interval construction are developed and compared using Monte Carlo simulation. The results show that either method may be safely used for confidence interval construction provided the number of twin pairs is large (> or =100) but that in smaller sample sizes the goodness-of-fit procedure is to be preferred on the grounds of validity. Other inference problems are also discussed, including point estimation, hypothesis testing and sample size estimation. An example is included.

Computer Simulation↗
PubMed2000

Testing the equality of two dependent kappa statistics.

Procedures are developed and compared for testing the equality of two dependent kappa statistics in the case of two raters and a dichotomous outcome variable. Such problems may arise when each of a sample of subjects are rated under two distinct settings, and it is of interest to compare the observed levels of inter-observer and intra-observer agreement. The procedures compared are extensions of previously developed procedures for comparing kappa statistics computed from independent samples. The results of a Monte Carlo simulation show that adjusting for the dependency between samples tends to be worthwhile only if the between-setting correlation is comparable in magnitude to the within-setting correlations. In this case, a goodness-of-fit procedure that takes into account the dependency between samples is recommended.

Analysis of Variance↗
PubMed2000

Cytotoxic aldehyde generation in heart following acute iron-loading.

Although the mechanism of myocardial failure following acute iron poisoning is not known, excess iron-catalyzed free radical generation is conjectured to play a role. The effects of time (0 to 360 minutes) on total iron concentrations, glutathione peroxidase activity, and cytotoxic aldehyde production in heart of mice (B6D2F1, n = 65) were first investigated following acute iron-loading (20 mg iron dextran i.p./mouse). In a subsequent experiment, the effects of dose (0 to 80 mg iron dextran i.p./mouse, n = 75) on the aforementioned parameters were investigated. Our results show that the concentrations of cytotoxic aldehydes: (1) significantly differ over-time, with corresponding increases in total concentrations of iron (r = 0.93, p < 0.001); and (2) increase parallel to the total dose of iron administered (r = 0.95, p < 0.001). Furthermore, dose-and time-dependent alterations to glutathione peroxidase activity are observed, which is most likely due to an acute up-regulation of the enzyme as an endogenous protective response to increased free radical activity in the heart subsequent to iron-loading. While no single mechanism is likely to account for the complex pathophysiology of acute iron-induced heart failure, our results shown that iron-loading can result in significant free radical generation, as quantified by cytotoxic aldehydes, in heart tissue of mice. This is the first report on the effects of time and dose on cytotoxic aldehyde generation and glutathione peroxidase activity in heart of mice following acute iron-loading.

Aldehydes↗
PubMed2000

The effect of collapsing multinomial data when assessing agreement.

BACKGROUND: In epidemiological studies researchers often depend on proxies to obtain information when primary subjects are unavailable. However, relatively few studies have performed formal statistical inference to assess agreement among proxy informants and primary study subjects. In this paper, we consider inference procedures for studies of interobserver agreement characterized by two raters and three or more outcome categories. Of particular interest is the consequence of dichotomizing such data on the expected confidence interval width for the kappa coefficient. The effect of dichotomization on sample size requirements for testing hypotheses concerning kappa is also evaluated. METHODS: Simulation studies were used to compare coverage levels and widths for constructing confidence intervals. Sample size requirements were compared for multinomial and dichotomous data. We illustrate our results using a published data set on drinking habits that assesses agreement among primary and proxy respondents. RESULTS: Our results show that when multinomial data are treated as dichotomous, not only do the expected confidence interval widths become greater, but the penalty in terms of larger sample size requirements for hypothesis testing can be severe. CONCLUSION: We conclude that there are clear advantages in preserving multinomial data on the original scale rather than collapsing the data into a binary trait.

Alcohol Drinking↗
PubMed2000

Systemic oxygen-free radical production in iron-loaded mice.

Although iron is an essential element for normal cell metabolism, in excess quantities it is highly cytotoxic and lethal. In fact, acute iron poisoning is a leading cause of overdose mortality in young children. Hereditary hemochromatosis, a disorder of iron metabolism, is currently the most prevalent genetic disorder in the world, which results in organ failure and premature mortality. Hence, an enhanced understanding of its pathogenesis is critical for providing safe and effective nursing care to affected individuals and their families. Although the exact mechanism of iron's toxicity is not known, it was hypothesized that chronic iron loading would result in increased tissue (heart, liver, and spleen) concentrations of iron and increased free radical production in a murine model (n = 20). Our results show that chronic iron loading results in highly significant dose-dependent increases in tissue concentrations of iron and systemic free radical generation (p < 0.001).

Analysis of Variance↗
PubMed2000

Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of injury and dysfunction in a murine model.

Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron-induced heart failure remains to be elucidated, the toxicity of iron in biological systems is believed to be attributed to its ability to catalyze the generation of oxygen-free radicals. In the current investigation, the dose-dependent effects of chronic iron-loading on heart tissue concentrations of iron, glutathione peroxidase (GPx) activity, free-radical production, and cardiac dysfunction were investigated in a murine model of iron-overload cardiomyopathy. It was shown that chronic iron-overload results in dose-dependent (a) increases in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx activity, (c) increased free-radical production, and (d) increased mortality. These findings show that the mechanism of iron-induced heart dysfunction involves in part free radical-mediated processes.

Animals↗
PubMed1999

Cardiac function and cytotoxic aldehyde production in a murine model of chronic iron-overload.

OBJECTIVES: To determine the relationship between the total chronic dose of iron administered, ex-vivo cardiac function and the concentrations of cytotoxic aldehydes in heart tissue of a murine model. METHODS: In the first experiment, 34 male B6D2F1 mice were randomized to receive intraperitoneal injections of 5, 10 or 20 mg of iron dextran for three weeks, or a placebo control. The mice were subsequently randomized to undergo ex-vivo assessment of cardiac function. In the second experiment, free radical generation, quantified by the presence of 20 separate cytotoxic aldehydes, was assessed in heart tissue of 40 mice that were randomized to receive chronic treatment with various concentrations of iron dextran (100 mg to 300 mg total chronic dose administered), placebo treatment with saline, or no treatment at all (baseline). RESULTS: Iron-loaded groups displayed dose-dependent depressions of heart rate, systolic pressure, developed pressure, coronary pressure, -dP/dt and +dP/dt, and increases in diastolic pressure. Monotonic dose-dependent increases in total heart aldehydes were observed in the iron-treated groups (r-0.97, p < 0.0001), whereas no significant differences were observed between baseline or time-placebo control groups. CONCLUSIONS: While no single mechanism is likely to account for the complex pathophysiology of iron-induced heart failure, our findings show that chronic iron-loading in a murine model results in dose-dependent alterations to cardiac function; and results in free radical mediated damage to the heart, as measured by excess concentrations of cytotoxic aldehyde-derived peroxidation products. This is the first description of the effects of excess iron on cardiac function assessed by an ex-vivo Langendorff technique in a murine model of chronic iron-overload.

Aldehydes↗
PubMed1999

Testing the equality of twin correlations with multinomial outcomes.

Twin studies are widely used to study genetic and environmental influences on human measurements. Correlations are often used in such studies to compare the levels of similarity between monozygotic and dizygotic twins with respect to a specified trait. In this paper, we compare three procedures for testing the equality of twin correlations when the outcome variable of interest is multinominal. One method is a likelihood ratio test based on an underlying Dirichlet-multinomial distribution. The second method is based on the estimated large sample variance of the estimated correlation, and the third method is based on a chi 2 goodness-of-fit test. The results of a Monte Carlo simulation show that the three methods have similar properties if the number of twin pairs is large (> 100), and the prevalence of the underlying trait is not extreme. Otherwise, the goodness-of-fit approach is to be preferred. We illustrate the methods by analyzing data from a previously published smoking study.

Analysis of Variance↗
PubMed1998

The synergistic effects of vitamin E and selenium in iron-overloaded mouse hearts.

OBJECTIVES: To determine whether supplementation with vitamin E and selenium can improve myocardial antioxidant defenses in iron-overloaded mouse hearts. INTERVENTIONS: Iron-overload state was created in B6D2F1 mice (n = 20) by daily injection of iron dextran (5 mg intraperitoneally/mouse) for four weeks. The mice were also simultaneously randomly assigned to receive vitamin E (alpha-tocopherol acetate, 40 mg intraperitoneally, n = 5), selenium (sodium selenite, 1 part/million orally, n = 5), both (vitamin E + selenium, n = 5) or iron-only treatment (n = 5). The hearts were harvested for determination of selenium concentration and glutathione peroxidase activity. In a subsequent study, 15 B6D2F1 mice were randomly assigned to receive daily injections of iron (n = 5) or iron and combined antioxidant treatment (vitamin E + selenium, n = 5), or to serve as controls (n = 5) for four weeks. The hearts were harvested for determination of total iron concentrations. MAIN RESULTS: Significantly greater concentrations of heart selenium and glutathione peroxidase activity were observed in groups supplemented with both agents, as opposed to iron-only treated or single supplemented mice. Significantly lower concentrations of iron were found in controls and in those receiving combined iron and antioxidant treatment (vitamin E + selenium) than in iron-only treated mice. CONCLUSIONS: Vitamin E and selenium function synergistically in the myocardium to provide important antioxidant defenses in iron-overload states, including increased concentrations of selenium, increased glutathione peroxidase activity and decreased concentrations of iron.

Animals↗
PubMed1995

The relationship of serum ferritin with sex and exercise in Canadians of Icelandic descent: implications for prevention of coronary artery disease.

OBJECTIVE: To investigate the relationship of serum ferritin with sex and exercise. DESIGN AND SETTING: A cross-sectional design study carried out in Winnipeg, Manitoba. SUBJECTS: Urban Canadians of Icelandic descent, aged 21 to 60 years, took part in this investigation. Subjects were stratified by age, sex and menstrual status. INTERVENTIONS: Venous blood samples from fasting subjects were drawn for serum ferritin, hemoglobin and hematocrit analyses. Various anthropomorphic measurements were taken, and subjects underwent submaximal cycle ergometry testing. A health and lifestyles questionnaire and a four-day prospective food record were administered. MAIN RESULTS: Mean serum ferritin levels obtained were 187.93 and 47.84 micrograms/L for males and females, respectively. Mean serum ferritin levels were 33.06 micrograms/L and 71.14 micrograms/L for premenopausal and postmenopausal females, respectively. The mean weekly consumption of alcohol was 190 mL/week and 80 mL/week for males and females, respectively. The mean dietary intake of iron was 27.3 and 18.9 mg/day for males and females, respectively. Males, but not females, who exercised 45 mins or more per week had significantly lower levels of serum ferritin than their sedentary counterparts. In males, hemoglobin, hematocrit and the consumption of alcohol were positively correlated with serum ferritin, while exercise time was negatively correlated with serum ferritin. A trend towards lower serum ferritin levels at higher workloads was observed in males, but did not reach statistical significance. In females, age and dietary intake of iron were found to be positively correlated with serum ferritin, while history of anemia, menstrual status and workload were negatively correlated with serum ferritin. CONCLUSIONS: These findings suggest that regular aerobic exercise may decrease iron stores in the body. This may be clinically significant since high serum ferritin has been cited as a risk factor for coronary artery disease.

Adult↗
PubMed1994

Promoting health in schools through a board game.

Primary prevention and health promotion have become salient topics in Canadian society and in nursing during the past two decades. The noncommunicable chronic diseases, such as heart disease and cancer, have been linked to specific lifestyle behaviors or habits, which often develop early in life. The success of public health efforts to improve the health status of all Canadians depends substantially on the success of educational programs directed toward children. Effective teaching strategies that seek to promote health and wellness in children need to be developed and empirically evaluated. Educational games may provide an efficient vehicle for carrying out developmentally specific nursing interventions in school settings. This article begins with a brief overview of the historical origins of games, along with their advantages and disadvantages as educational strategies. The results of a pretest-posttest control group design study that evaluated the effectiveness of a board game as a primary prevention teaching strategy with 23 sixth grade children in Winnipeg, Manitoba are presented. The experimental group had significant gains in knowledge related to anatomy and physiology, diet, and lifestyle risk factors associated with the development of heart disease and cancer.

Child↗
PubMedDate not supplied

A biochemical, histochemical, and electron microscopic study on the effects of iron-loading on the hearts of mice.

Acute iron poisoning and chronic iron overload are well-known causes of myocardial failure. Although the exact mechanism is not known, excess iron-catalyzed free radical generation is conjectured to play a role in damaging the myocardium and altering cardiac function. We report here on the effects of acute and chronic iron-loading on the total iron concentration, glutathione peroxidase activity, and cytotoxic aldehyde production in the heart of a murine model (n = 35). Light microscopic examination for the presence of ferrous and ferric iron was undertaken following histochemical staining for these species. In addition, examination of representative samples by transmission electron microscopy was performed. Our findings show that iron-loading can result in significant increases in total iron concentrations, alterations to glutathione peroxidase activity, and increases in cytotoxic aldehyde concentrations in the hearts of mice. Furthermore, we observe that iron-loading can significantly alter and damage various cellular constituents (e.g., mitochondria, lysosomes, sarcoplasmic reticulum) and this may have bearing on the mechanism of iron-induced heart failure.

Animals↗
PubMedDate not supplied

Selenium and glutathione peroxidase with beta-thalassemia major.

BACKGROUND: Chronic iron-overload is a major cause of organ failure and mortality worldwide, but its pathogenesis remains to be elucidated. OBJECTIVES: To examine the relationship between various measures of body iron burden, selenium concentrations and glutathione peroxidase (GPx) activity in patients with beta-thalassemia major. METHODS: An age- and gender-matched case control study was conducted to examine the relationship between various measures of body iron burden (serum ferritin, transferrin saturation, total serum iron), plasma concentrations of selenium and glutathione peroxidase (GPx) activity in patients with homozygous beta-thalassemia major (N = 20) and healthy controls (N = 10). Ten patients received the experimental oral chelator L1 and ten received chelation therapy with subcutaneous desferal. RESULTS: Significantly decreased plasma concentrations of selenium (microg/L) were observed in patients chelated with L1 (1.4 +/- 0.2) or desferal (1.4 +/- 0.1), in comparison to healthy controls (1.8 +/- 0.1, p < 0.01). Significantly decreased plasma activity of GPx (microg/L) was observed in patients chelated with L1 (166 +/- 43) or desferal (178 +/- 46), in comparison to healthy controls (296 +/- 22, p < 0.001). Significantly increased concentrations of all measures of body iron burden were observed in beta-thalassemia patients, in comparison to healthy controls (p < 0.001). CONCLUSION: Patients with beta-thalassemia major and chronic iron-overload have decreased concentrations of the essential element selenium and the protective selenium-dependent antioxidant enzyme GPx. Additional research examining the effects of dietary antioxidant supplementation with selenium on these aforementioned parameters in patients with beta-thalassemia major and iron-overload is warranted.

Adult↗