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Biomedical subjects

David Cox

Publications and source records attributed to David Cox.

At least 19 recordsLinked to original sources
PubMed2005

Usefulness of the presence of peripheral vascular disease in predicting mortality in acute myocardial infarction patients treated with primary angioplasty (from the Primary Angioplasty in Myocardial Infarction Database).

Patients with acute myocardial infarction (AMI) often have multiple co-morbidities that influence outcome. We sought to evaluate the impact of peripheral vascular disease (PVD) on the outcome of patients with AMI treated with primary angioplasty. We evaluated 3,716 patients with AMI who underwent emergency catheterization with planned primary angioplasty in the Primary Angioplasty in Myocardial Infarction trials. Patients with a history of PVD (claudication, stroke, or transient ischemic attack) were compared with patients without PVD. Of the 3,716 patients, 394 (10.6%) had PVD and were older, more often women, and more frequently had a history of diabetes mellitus, hypertension, smoking, congestive heart failure, angina, myocardial infarction, and coronary revascularization. They presented more often with a heart rate >100 beats/min, Killip class >1, lower ejection fraction, and multivessel disease. No difference was found in stent use, final percentage of stenosis, or Thrombolysis In Myocardial Infarction 3 flow. Patients with PVD had a twofold increased in-hospital mortality (5.3% vs 2.6%, p = 0.0021). The difference remained significant at 1 month, 6 months, and 1 year (12.6% vs 6%, p < 0.0001). In multivariate logistic regression analysis, a history of PVD was an independent predictor of in-hospital mortality and death at 1 year (odds ratio 1.64, 95% confidence interval 1.04 to 2.57, p = 0.032). In conclusion, patients with AMI with PVD have increased co-morbidities and higher mortality despite treatment with primary angioplasty. The presence of PVD is an independent predictor of in-hospital mortality and death at 1 year.

Aged↗
PubMed2005

Effectiveness of the concomitant use of bivalirudin and drug-eluting stents (from the prospective, multicenter BivAlirudin and Drug-Eluting STents [ADEST] study).

Sirolimus-eluting stents (SESs) reduce restenosis compared with bare metal stents. Safety issues with drug-eluting stents are particularly important given concerns of possible increased thrombogenicity. Compared with heparin plus glycoprotein IIb/IIIa inhibitors, the direct thrombin inhibitor bivalirudin has been shown to reduce the risk of hemorrhagic complications in patients receiving bare metal stents, with similar efficacy in preventing ischemic complications. The safety and efficacy of percutaneous coronary intervention (PCI) with SESs and bivalirudin anticoagulation have not been prospectively studied. This prospective study performed at 9 United States hospitals evaluated 1,182 patients referred for PCI with SESs in whom the procedural anticoagulant was bivalirudin. Clopidogrel was administered before PCI in 79% of patients, and only 5.3% received procedural glycoprotein IIb/IIIa inhibitors. At 30 days, major adverse cardiac events occurred in 7.1% of patients, including 0.3% mortality, 4.4% myocardial infarction (defined as creatine kinase-MB >3x normal), 1.7% target vessel revascularization, and 0.6% stent thrombosis. Major bleeding occurred in only 0.8% of patients. Thus, use of bivalirudin as the procedural anticoagulant to support SES implantation in a "real world" population of patients undergoing PCI results in low rates of major adverse cardiac events, stent thrombosis, and major bleeding.

Angioplasty, Balloon, Coronary↗
PubMed2005

Comparison of the prognostic effect of left versus right versus no bundle branch block on presenting electrocardiogram in acute myocardial infarction patients treated with primary angioplasty in the primary angioplasty in myocardial infarction trials.

The presence of bundle branch block (BBB) has been associated with poor outcomes in patients who have acute myocardial infarction. Whether this is true in the angioplasty era is not known. We sought to evaluate the outcome of patients with acute myocardial infarction and BBB who were treated with primary angioplasty. We evaluated 3,053 patients who underwent emergency catheterization in the PAMI trials. Patients who had left BBB (n = 48, 1.6%) on presenting electrocardiogram were compared with patients who had right BBB (n = 95, 3.1%) or no BBB (n = 2,910, 95.3%). Patients who had BBB were older and more frequently had diabetes mellitus, peripheral vascular disease, and previous coronary artery bypass grafting. They had lower ejection fraction and more multivessel disease. There were no significant differences in door-to-balloon time, final Thrombolysis In Myocardial Infarction flow grade or stent use. In-hospital major adverse cardiac events (death, ischemic target vessel revascularization, and reinfarction) were higher in patients who had BBB due primarily to increased in-hospital death (left BBB 14.6%, right BBB 7.4%, no BBB 2.8%, p < 0.0001). In multivariate logistic regression analysis, left BBB was an independent predictor of in-hospital death (odds ratio 5.53, 95% confidence interval 1.89 to 16.1, p = 0.002). In conclusion, patients who have acute myocardial infarction and BBB have increased co-morbidities and higher mortality rates despite treatment with primary angioplasty. Despite early identification of multivessel disease with triage to angioplasty or coronary artery bypass grafting, if necessary, similar treatment times, and final Thrombolysis In Myocardial Infarction grade 3 flow, the presence of left BBB on admission electrocardiogram in patients who have acute myocardial infarction is an independent predictor of in-hospital mortality. Because 85% of deaths in patients who have left BBB occur within the first week, these patients should be recognized early and receive prompt and aggressive treatment.

Aged↗
PubMed2005

Genome-wide definitive haplotypes determined using a collection of complete hydatidiform moles.

We present genome-wide definitive haplotypes, determined using a collection of 74 Japanese complete hydatidiform moles, each carrying a genome derived from a single sperm. The haplotypes incorporate 281,439 common SNPs, genotyped with a high throughput array-based oligonucleotide hybridization technique. Comparison of haplotypes inferred from pseudoindividuals (constructed from randomized mole pairs) with those of moles showed some switch errors in resolution of phases by the computational inference method. The effects of these errors on local haplotype structure and selection of tag SNPs are discussed. We also show that definitive haplotypes of moles may be useful for elucidation of long-range haplotype structure, and should be more effective for detecting extended haplotype homozygosity indicative of positive selection.

Female↗
PubMed2005

Left ventricular remodeling and systolic deterioration in acute myocardial infarction: findings from the Stent-PAMI Study.

BACKGROUND: Left ventricular systolic deterioration (LVSD) develops in some patients despite successful percutaneous intervention and medical therapy for myocardial infarction (MI). We sought to determine predictors of LVSD by comparing demographic, procedural, angiographic variables, and 6-month major adverse cardiac events (MACE) in patients with and without LVSD after MI. METHODS: We performed a posthoc analysis of patients prospectively enrolled in the Stent-PAMI trial if they had successful percutaneous intervention for MI (<50% residual stenosis and TIMI-3 grade flow), normal left ventricular systolic function on index ventriculogram, and protocol driven coronary angiography with ventriculography at 6 months. We defined LVSD as an absolute decrease in ejection fraction > or =15% compared to baseline value. RESULTS: Of the 900 patients enrolled in Stent-PAMI, 187 patients met the inclusion criteria. LVSD developed in 30 patients (16%) and occurred independent of demographic, procedural, angiographic variables, and 6-month MACE. Multivariate predictors of LVSD were higher baseline ejection fraction (P = 0.0065, OR 1.09; 95% CI = 1.02-1.16) and peak creatine phosphokinase (CPK) level (P = 0.0022, OR 1.04; 95% CI = 1.02-1.07). CONCLUSIONS: LVSD occurs in a minority of patients despite successful mechanical reperfusion and occurred independent of procedural, angiographic variables, target vessel revascularization, reinfarction, and combined MACE. Infarct size (determined by peak CPK) and high baseline ejection fraction predicted development of LVSD at 6 months. LVSD in this population likely occurred by negative left ventricular remodeling.

Creatine Kinase↗
PubMed2004

Frequency of returning to work one and six months following percutaneous coronary intervention for acute myocardial infarction.

We conducted an analysis of the frequency and variables associated with early (after 1 month) and late (after 6 months) return to work after percutaneous coronary intervention for acute myocardial infarction in patients who had been randomized in the Stent Primary Angioplasty in Myocardial Infarction trial. Of 450 patients who were employed before the acute myocardial infarction, 230 (51%) returned to work within 1 month with no increases in in-hospital and 1- or 6-month event rates compared with those who did not return to work. Multivariate analysis showed that predictors of early return to work were employment in the United States, no history of smoking, and single-vessel coronary disease. At 6 months, 353 of 435 patients (78%) had returned to work, and multivariate analysis showed that predictors of late return to work were employment in the United States and absence of angina.

Absenteeism↗
PubMed2004

2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution.

4-Methylaminopyridine (4-MAP) (5) is a potent but nonselective nitric oxide synthase (NOS) inhibitor. While simple N-methylation in this series results in poor activity, more elaborate N-substitution such as with 4-piperidine carbamate or amide results in potent and selective inducible NOS inhibition. Evidently, a flipping of the pyridine ring between these new inhibitors allows the piperidine to interact with different residues and confer excellent selectivity.

Aminopyridines↗
PubMed2004

Sustained ventricular tachycardia or fibrillation in the cardiac catheterization laboratory among patients receiving primary percutaneous coronary intervention: incidence, predictors, and outcomes.

OBJECTIVES: We sought to evaluate the incidence, predictors, and outcomes of ventricular tachycardia and/or ventricular fibrillation (VT/VF) in the cardiac catheterization laboratory among patients undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Although VT/VF has been known to occur during primary PCI, the current data do not identify patients at risk for these arrhythmias or the outcomes of such patients. METHODS: We evaluated 3065 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI) trials, who underwent primary PCI to evaluate the associations of VT/VF and the influence of these arrhythmias on in-hospital and one-year outcomes. RESULTS: In patients undergoing primary PCI, VT/VF occurred in 133 (4.3%). Multivariate analysis identified the following as independent correlates of VT/VF: smoking (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.26 to 3.02), lack of preprocedural beta-blockers (OR 2.34, 95% CI 1.35 to 4.07), time from symptom onset to emergency room of <or=180 min (OR 2.63, 95% CI 1.42 to 4.89), initial Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 (OR 2.06, 95% CI 1.23 to 3.47), and right coronary artery-related infarct (OR 1.93, 95% CI 1.25 to 2.99). Although patients with VT/VF had a higher incidence of bradyarrhythmias, hypotension, cardiopulmonary resuscitation, and endotracheal intubation in the catheterization laboratory, their in-hospital and one-year adverse outcomes were similar to those of the cohort without these arrhythmias. CONCLUSIONS: Our findings suggest that the incidence of VT/VF during primary PCI is low, indicating that these arrhythmias do not influence PCI success or in-hospital or one-year outcomes. Our data further help identify patients at risk of VT/VF during primary PCI and suggest that pretreatment with beta-blockers should be strongly considered to reduce these arrhythmias.

Aged↗
PubMed2004

Contextually evoked object-specific responses in human visual cortex.

Human visual recognition processes are remarkably robust and can function effectively even under highly degraded viewing conditions. Contextual information may play a critical role in such circumstances. Here, we provide neurophysiological evidence that contextual cues can elicit object-specific neural responses, which have hitherto been believed to be based on intrinsic cues alone. Specifically, we find that the "fusiform face area" (FFA) maintains its selectivity for faces without regard to whether the faces are defined intrinsically or contextually. This finding further elucidates the role of the FFA and reveals neural correlates of contextual processing in the service of robust object recognition.

Adult↗
PubMed2004

Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.

Actins↗
PubMed2003

Prognostic significance of transient no-reflow during primary percutaneous coronary intervention for ST-elevation acute myocardial infarction.

We found that of 1,192 patients who underwent primary percutaneous coronary intervention and who had final Thrombolysis In Myocardial Infarction grade 3 flow at the conclusion of the procedure, transient no-reflow occurred in 16 patients (1.3%). Compared with patients without transient no-reflow during the procedure, those with transient no-reflow had higher in-hospital (2% vs 13%, p=0.04) and 6-month mortality (3% vs 31%, adjusted odds ratio 5.4, 95% confidence interval 1.01 to 29.0, p=0.0001).

Angioplasty, Balloon↗
PubMed2003

Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

OBJECTIVES: The purpose of this study was to determine the clinical and angiographic correlates and outcomes of patients with suboptimal coronary flow after primary percutaneous coronary interventions (PCI). BACKGROUND: The clinical and angiographic correlates and outcomes of Thrombolysis in Myocardial Infarction (TIMI) < or =2 flow in patients treated with primary PCI are not known. METHODS: We evaluated 3,362 patients with ST elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction trials, who underwent primary PCI. RESULTS: Post-procedural final TIMI < or =2 flow occurred in 232 (6.9%) patients. Multivariate analysis identified age > or =70 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), diabetes (OR 1.9; 95% CI, 1.3 to 2.7), symptom onset to emergency room presentation (OR 1.1; 95% CI, 1.1 to 1.2); initial TIMI < or =1 flow (OR 3.2; 95% CI, 1.9 to 5.5), and left ventricular ejection fraction <50% (OR 1.7; 95% CI, 1.2 to 2.4) as independent correlates of final TIMI < or =2 flow. In-hospital (composite of reinfarction, ischemic target vessel revascularization, or death, as well as these events individually) and one-year (reinfarction and/or death) events occurred more frequently in patients with TIMI < or =2 flow. The Cox proportional hazards model identified TIMI < or =2 flow to be independently associated with one-year mortality (hazard ratio 3.8, 95% CI, 2.5 to 5.7). CONCLUSIONS: Final TIMI < or =2 flow, although uncommon after primary PCI, was strongly associated with hospital and one-year adverse events. The clustering of final TIMI < or =2 flow in high-risk groups may partially explain the poor prognosis of these patients. Awareness of these risk factors may be useful to clinicians to triage and treat patients undergoing primary PCI.

Aged↗
PubMed2003

Frequency, determinants, and clinical implications of residual intracoronary thrombus following primary angioplasty for acute myocardial infarction.

The presence of intracoronary thrombus after percutaneous coronary intervention (PCI) worsens clinical outcomes. We performed this study to assess the incidence of intracoronary thrombus after primary angioplasty for acute myocardial infarction (AMI) and the clinical impact of nonocclusive thrombus. In 2,148 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI)-2, Stent PAMI, and PAMI No-Surgery-On-Site trials, we compared clinical and angiographic characteristics of 131 patients (6%) who had angiographically visible thrombus after PCI with those who did not (n = 2,017). In the subset of 2,115 patients with post-PCI Thrombolysis In Myocardial Infarction (TIMI) 2 or 3 flow, we assessed the impact of post-PCI thrombus (n = 110) on in-hospital, 1-month, and 1-year outcomes (reinfarction, ischemic target vessel revascularization [I-TVR], death, and major adverse cardiovascular events [MACEs] [i.e., death, reinfarction, or I-TVR]). Lack of stent use, presence of thrombus before PCI, and no history of PCI were independent correlates of post-PCI thrombus. Patients with nonocclusive thrombus after PCI had more reinfarctions during the index hospitalization (5.5% vs 2.0%, p = 0.03) and at 1 month (6.8% vs 2.3%, p = 0.01) and had nonsignificantly higher I-TVR (during hospitalization 5.5% vs 2.8%, p = 0.13; at 1 month 5.9% vs 3.4%, p = 0.17), but similar mortality and MACE rates as those without post-PCI thrombus. In multivariate analysis, post-PCI thrombus was not a significant predictor of in-hospital or 1-month reinfarction. At 1 year, clinical outcomes were similar between patient groups (reinfarction 8.3% vs 4.7%, p = 0.14; I-TVR 12.5% vs 12.1%, p = 0.91; death 5.9% vs 5.0%, p = 0.68; and MACEs 21% vs 18%, p = 0.54). We conclude that residual intracoronary thrombus after primary angioplasty is relatively uncommon. In patients who achieve TIMI 2 or 3 flow after PCI, intracoronary thrombus is associated with worse cardiovascular outcomes. However, differences in outcomes between patients with and without residual thombus are related to baseline clinical differences rather than thrombus per se.

Angioplasty, Balloon, Coronary↗
PubMed2003

Comparison of outcomes of diabetic and nondiabetic patients undergoing primary angioplasty for acute myocardial infarction.

We sought to determine whether diabetes mellitus independently conferred poor prognosis in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). In 3,742 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI) studies with the intention of undergoing primary PCI, we compared in-hospital mortality, 6-month mortality, and 6-month major adverse cardiovascular events (MACEs), i.e., composite of death, reinfarction, or ischemic target vessel revascularization (TVR), between diabetics (n = 626, 17%) and nondiabetics (n = 3,116, 83%). We evaluated the independent impact of diabetes on outcomes after adjustment for baseline clinical and angiographic differences. Diabetics had worse baseline clinical characteristics, longer pain onset-to-hospital arrival time, and longer door-to-balloon time. They had more multivessel coronary disease and lower left ventricular ejection fractions, but better baseline Thrombolysis In Myocardial Infarction (TIMI) flow. Diabetics underwent primary PCI less often (88% vs 91%, p = 0.01). During the index hospitalization, diabetics were more likely to die (4.6% vs 2.6%, p = 0.005). During 6-month follow-up, diabetics had higher incidences of death (8.1% vs 4.2%, p <0.0001) and MACEs (18% vs 14%, p = 0.036). In multivariate analysis, diabetes was independently associated with 6-month mortality (hazard ratio 1.53, 95% confidence interval 1.03 to 2.26, p = 0.03), but not with in-hospital mortality or 6-month MACEs. We conclude that diabetics with AMI have less favorable baseline characteristics and are less likely to undergo primary PCI than nondiabetics. Despite excellent angiographic results, diabetics had significantly worse 6-month mortality.

Aged↗
PubMed2003

Effects of prior beta-blocker therapy on clinical outcomes after primary coronary angioplasty for acute myocardial infarction.

We hypothesized that pretreatment with beta blockers may improve clinical outcomes after primary angioplasty for acute myocardial infarction. We pooled clinical, angiographic, and outcomes data on 2,537 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI), PAMI-2, and Stent PAMI trials. We classified patients into a beta group (n = 1,132) if they received beta-blocker therapy before primary angioplasty or a no-beta group (n = 1,405) if they did not. We evaluated procedural complications and in-hospital and 1-year outcomes (death and major adverse cardiac events [death, reinfarction, target vessel revascularization, or stroke]) between groups. Beta patients were younger, had higher systolic blood pressure and heart rate, and were more likely to be in Killip class I at admission. They had lower left ventricular ejection fraction, greater door-to-balloon time, greater likelihood of having a left anterior descending artery culprit lesion, but a similar incidence of Thrombolysis In Myocardial Infarction 3 flow after angioplasty (92.6% vs 92.7%, p = 0.91). The beta group had less procedural complications (23% vs 34%, p <0.0001) and a lower incidence of death (1.8% vs 3.7%, p = 0.0035) and major adverse cardiac events (5.5% vs 7.8%, p = 0.027) during hospitalization. At 1 year, mortality remained lower in beta patients (4.9% vs 6.7%, log-rank p = 0.055). After adjustment for baseline differences, beta patients had significantly lower in-hospital mortality (odds ratio 0.41; 95% confidence interval 0.20 to 0.84; p <0.0148) and nonsignificantly lower 1-year mortality (odds ratio 0.72; 95% confidence interval 0.47 to 1.08; p = 0.11). Thus, pretreatment with beta blockers has an independent beneficial effect on short-term clinical outcomes in patients undergoing primary angioplasty for acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed2003

Analysis of a key regulatory region upstream of the Myf5 gene reveals multiple phases of myogenesis, orchestrated at each site by a combination of elements dispersed throughout the locus.

Myf5 is the first myogenic regulatory factor to be expressed in the mouse embryo and it determines the entry of cells into the skeletal muscle programme. A region situated between -58 kb and -48 kb from the gene directs Myf5 transcription at sites where muscles will form. We now show that this region consists of a number of distinct regulatory elements that specifically target sites of myogenesis in the somite, limbs and hypoglossal cord, and also sites of Myf5 transcription in the central nervous system. Deletion of these sequences in the context of the locus shows that elements within the region are essential, and also reveals the combinatorial complexity of the transcriptional regulation of Myf5. Both within the -58 kb to -48 kb region and elsewhere in the locus, multiple sequences are present that direct transcription in subdomains of a single site during development, thus revealing distinct phases of myogenesis when subpopulations of progenitor cells enter the programme of skeletal muscle differentiation.

Animals↗
PubMed2002

Comparison of effectiveness of primary angioplasty for proximal versus distal right coronary artery culprit lesion during acute myocardial infarction.

From the cohort of 4,023 patients enrolled in the Primary Angioplasty for Myocardial Infarction (PAMI) trials, we pooled clinical, angiographic, and outcomes data on 1,521 patients with culprit lesions in the right coronary artery (RCA). We compared angiographic results, procedural complications, and in-hospital and 1-year clinical outcomes between patients with proximal RCA (n = 572) versus nonproximal RCA culprit lesions (n = 949). Patients with proximal RCA culprit lesions were older, had lower systolic blood pressure, greater diameter stenosis, and were less likely to have Thrombolysis In Myocardial Infarction (TIMI) 2 or 3 flow (19% vs 31%; p <0.0001) before percutaneous coronary intervention (PCI). After PCI, the incidence of TIMI 3 flow (94% vs 93%) was similar between groups. Patients with proximal RCA lesions were more likely to have bradyarrhythmias (30% vs 23%, p = 0.016) and require an intra-aortic balloon pump (IABP; 4.6% vs 2%, p = 0.034) during PCI. In-hospital complications, including mortality (2.3% vs 2.2%) and reinfarction (1.4% vs 1.1%), and the 1-year incidence of death, reinfarction, ischemia driven target vessel revascularization, and major adverse cardiovascular events were similar between groups. After adjustment for baseline differences, proximal RCA location of the culprit lesion was independently associated with greater IABP use (odds ratio 2.41, 95% confidence interval 1.04 to 5.58) but not with bradyarrhythmias during PCI. Thus, in patients with acute myocardial infarction referred for primary angioplasty, proximal RCA location of the culprit lesion is associated with excellent clinical outcomes that are similar to nonproximal RCA lesions.

Aged↗