Biomedical subjects

Mark Tripputi

Publications and source records attributed to Mark Tripputi.

5 recordsLinked to original sources

PubMed2006

A summarization approach for Affymetrix GeneChip data using a reference training set from a large, biologically diverse database.

BACKGROUND: Many of the most popular pre-processing methods for Affymetrix expression arrays, such as RMA, gcRMA, and PLIER, simultaneously analyze data across a set of predetermined arrays to improve precision of the final measures of expression. One problem associated with these algorithms is that expression measurements for a particular sample are highly dependent on the set of samples used for normalization and results obtained by normalization with a different set may not be comparable. A related problem is that an organization producing and/or storing large amounts of data in a sequential fashion will need to either re-run the pre-processing algorithm every time an array is added or store them in batches that are pre-processed together. Furthermore, pre-processing of large numbers of arrays requires loading all the feature-level data into memory which is a difficult task even with modern computers. We utilize a scheme that produces all the information necessary for pre-processing using a very large training set that can be used for summarization of samples outside of the training set. All subsequent pre-processing tasks can be done on an individual array basis. We demonstrate the utility of this approach by defining a new version of the Robust Multi-chip Averaging (RMA) algorithm which we refer to as refRMA. RESULTS: We assess performance based on multiple sets of samples processed over HG U133A Affymetrix GeneChip arrays. We show that the refRMA workflow, when used in conjunction with a large, biologically diverse training set, results in the same general characteristics as that of RMA in its classic form when comparing overall data structure, sample-to-sample correlation, and variation. Further, we demonstrate that the refRMA workflow and reference set can be robustly applied to naïve organ types and to benchmark data where its performance indicates respectable results. CONCLUSION: Our results indicate that a biologically diverse reference database can be used to train a model for estimating probe set intensities of exclusive test sets, while retaining the overall characteristics of the base algorithm. Although the results we present are specific for RMA, similar versions of other multi-array normalization and summarization schemes can be developed.

Algorithms↗

PubMed2004

Postmenopausal hormone therapy is associated with atherosclerosis progression in women with abnormal glucose tolerance.

BACKGROUND: Abnormal glucose tolerance (AGT; diabetes or impaired glucose tolerance) is associated with increased risk of cardiovascular disease, especially in women. Cardiovascular disease rates in women increase after menopause. The Women's Health Initiative found that postmenopausal hormone therapy (PHT) increased the risk of cardiovascular disease and that effects in diabetic women did not differ from those in women without diabetes. In this study, we hypothesized that PHT would have a worse effect on disease among women with AGT. METHODS AND RESULTS: We randomly assigned 423 postmenopausal women with angiographically defined atherosclerosis (321 women had exit angiograms) with (n=140) or without (n=181) AGT to receive estrogen, estrogen plus progestin, or a placebo for 2.8+/-0.9 years. LDL was lower and HDL and triglycerides were higher after PHT in non-AGT and AGT women, but more adverse changes occurred in C-reactive protein and fibrinogen in women with AGT (P=0.11 and P=0.02 for interactions). PHT had no effect on fasting glucose or insulin concentrations in women without AGT, but in women with AGT, fasting glucose levels, insulin concentration, and insulin resistance as assessed by the HOMA (homeostasis model) calculation decreased slightly (P=0.28, P=0.25, P=0.14 for interaction, respectively). Atherosclerotic progression was greater in women with AGT. Atherosclerotic progression in previously nondiseased segments was enhanced by PHT to a greater extent in women with AGT (P=0.11 for interaction). CONCLUSIONS: PHT is associated with a worsening of coronary atherosclerosis and exacerbation of the profile of inflammatory markers in women with AGT. Therefore, PHT is not warranted for use in diabetic women. Further study is needed to explore the improvement in insulin resistance and glycemia that appears to occur with PHT in women with AGT.

Adult↗

PubMed2004

Remnant-like lipoproteins, hormone therapy, and angiographic and clinical outcomes: the Women's Angiographic Vitamin & Estrogen Trial.

BACKGROUND: Little is known about the impact of post-menopausal hormone therapy on remnant-like particle (RLP) concentrations and about the relationship between RLP concentration and angiographic progression of coronary artery disease and clinical events in women. METHODS: RLP cholesterol and triglyceride levels were measured at baseline and 3 months after randomization in 397 post-menopausal women enrolled in The Women's Angiographic Vitamin & Estrogen (WAVE) trial. Correlates of baseline RLP levels and changes in levels with post-menopausal hormone therapy were determined with multiple linear regression. Coronary angiography was performed at baseline and after a mean of 2.9 years. Changes in minimal and average luminal diameter were modeled with multivariate linear regression, clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death) with multiple logistic regression. RESULTS: The mean subject age was 65 years, 66% of subjects were white, 18% of subjects smoked, most subjects were overweight or obese, and 35% of subjects had diabetes mellitus. RLP cholesterol (0.277 +/- 0.254 mmol/L) and triglyceride (0.386 +/- 0.552 mmol/L) levels corresponded approximately to the 90th percentile in women in the Framingham study. RLP levels did not change significantly with hormone therapy. RLP levels at baseline, changes in RLP levels, and on treatment RLP levels did not relate to angiographic changes or clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death). CONCLUSIONS: RLP levels were high among post-menopausal women enrolled in the WAVE study, were not affected by hormone therapy, and did not relate to angiographic progression of coronary artery disease or clinical outcomes.

Aged↗

PubMed2004

The effect of vitamin therapy on the progression of coronary artery atherosclerosis varies by haptoglobin type in postmenopausal women.

OBJECTIVE: Antioxidant trials have not demonstrated efficacy in slowing cardiovascular disease but could not rule out benefit for specific patient subgroups. Antioxidant therapy reduces LDL oxidizability in haptoglobin 1 allele homozygotes (Hp 1-1), but not in individuals with the haptoglobin 2 allele (Hp 2-1 or Hp 2-2). We therefore hypothesized that haptoglobin type would be predictive of the effect of vitamin therapy on coronary atherosclerosis as assessed by angiography. RESEARCH DESIGN AND METHODS: We tested this hypothesis in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a prospective angiographic study of vitamins C and E with or without hormone replacement therapy (HRT) in postmenopausal women. Haptoglobin type was determined in 299 women who underwent baseline and follow-up angiography. The annualized change in the minimum luminal diameter (MLD) was examined in analyses stratified by vitamin use, haptoglobin type, and diabetes status. RESULTS: We found a significant benefit on the change in MLD with vitamin therapy as compared with placebo in Hp 1-1 subjects (0.079 +/- 0.040 mm, P = 0.049). This benefit was more marked in diabetic subjects (0.149 +/- 0.064 mm, P = 0.021). On the other hand, there was a trend toward a more rapid decrease in MLD with vitamin therapy in Hp 2-2 subjects, which was more marked in diabetic subjects (0.128 +/- 0.057 mm, P = 0.027). HRT had no effect on these outcomes. CONCLUSIONS: The relative benefit or harm of vitamin therapy on the progression of coronary artery stenoses in women in the WAVE study was dependent on haptoglobin type. This influence of haptoglobin type seemed to be stronger in women with diabetes.

Aged↗

PubMed2003

Metabolic syndrome and coronary angiographic disease progression: the Women's Angiographic Vitamin & Estrogen trial.

BACKGROUND: The metabolic syndrome is a cluster of clinical characteristics thought to be associated with increased coronary risk. This analysis evaluates angiographic progression of coronary disease in women who are postmenopausal with and without the metabolic syndrome enrolled in the Women's Angiographic Vitamin & Estrogen (WAVE) trial, a randomized, controlled trial of hormone therapy and antioxidant vitamins. METHODS: A total of 425 women who are postmenopausal and have angiographic coronary disease were enrolled at 7 clinics between July 1997 and August 1999. Women were categorized as having the metabolic syndrome when they met the National Cholesterol Education Program Adult Treatment Panel III definition. Coronary angiograms were performed at baseline and after 2.8 +/- 0.9 years (mean +/- SD). Quantitative coronary angiographic analysis was performed at a core laboratory. RESULTS: Women with the metabolic syndrome (177/294, 60%) were more likely to be taking cholesterol-lowering medication (65% vs 51%, P =.01) and had higher body mass index (33 +/- 6 vs 28 +/- 6 kg/m(2), P <.001). The mean reduction in minimum lumen diameter was greater (-0.041 +/- 0.151 vs -0.023 +/- 0.148 mm/year, P =.33) and new lesions were more frequent (34% vs 23%, P =.054) in women with the metabolic syndrome. In multivariate analysis, the metabolic syndrome was not an independent predictor of angiographic disease progression. However, clinical events (myocardial infarction, stroke, or coronary death) were more frequent among women with the metabolic syndrome (P =.02). CONCLUSION: The metabolic syndrome was prevalent among postmenopausal women with coronary disease enrolled in the WAVE trial. Having the metabolic syndrome was not independently associated with changes in minimum lumen diameter or the development of new or progressing coronary lesions, but did confer an increased risk of clinical cardiovascular events.

Aged↗