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Biomedical subjects

Stephen Ellis

Publications and source records attributed to Stephen Ellis.

16 recordsLinked to original sources
PubMed2006

In vivo analysis of the anatomical relationship of coronary sinus to mitral annulus and left circumflex coronary artery using cardiac multidetector computed tomography: implications for percutaneous coronary sinus mitral annuloplasty.

OBJECTIVES: We sought to determine the in vivo anatomical relationships between mitral annulus (MA) and coronary sinus (CS) as well as CS and left circumflex coronary artery using cardiac computed tomography. BACKGROUND: Percutaneous treatment of mitral regurgitation (MR) by annuloplasty via CS is under development. Success of such treatment depends on the close anatomical proximity of the MA to the CS. The in vivo data regarding this anatomical relationship in humans are scant. We investigated this relationship using contrast multidetector computed tomography. METHODS: We studied 25 normal individuals and 11 patients with severe MR (3 to 4+) due to mitral valve prolapse. Separation between MA and CS was measured in standard planes, in 4-chamber (4C), 2-chamber (2C), and 3-chamber views. Distance from ostium of CS to the intersection with left circumflex (LCX), and anatomical relation of LCX and CS were determined using 3-dimensional mapping (Philips Brilliance, Philips Medical Systems, Amsterdam, the Netherlands). RESULTS: There was significant variance of CS to MA separation at all planes. Separation of CS and MA was increased in lateral location (4C) and decreased in posterior location (2C) in the MR group with increase in MA size. Left circumflex artery crossed between CS and MA in 80% of patients. The LCX crossed CS at a variable distance from the ostium of CS (86.5 +/- 21 mm, range 37 to 123 mm) CONCLUSIONS: There is significant variability in the relation of CS to MA in humans. Coronary sinus to MA distance increases in patients with severe MR and annular dilation, mainly in the posterolateral location. The left circumflex crosses under the CS the majority of times, but with a significant variability in the location where it crosses the CS. These anatomical features should be taken into consideration while selecting percutaneous treatment strategies for mitral valve repair.

Adult↗
PubMed2006

Validation of three-dimensional cardiac image integration: use of integrated CT image into electroanatomic mapping system to perform catheter ablation of atrial fibrillation.

INTRODUCTION: Accurate visualization of the complex left atrial (LA) anatomy and the location of an ablation catheter within the chamber is important in the success and safety of ablation for atrial fibrillation (AF). We describe the integration of CT into an electroanatomic mapping (EAM) system and its validation in patients undergoing catheter ablation for AF. METHODS AND RESULTS: Thirty patients (59.2 +/- 8 years, 25 M) with paroxysmal (12) and persistent (18) AF underwent ablation using CT image integration into an electroanatomic mapping system. CT registration using the pulmonary veins as markers (landmark) was achieved with an error of 6.4 +/- 2.8 mm with repeat registration required in two patients. Registration of the CT by best fit to a electroanatomic geometry (surface) was achieved with an error of 2.3 +/- 0.4 mm. There was no significant difference in the regional LA registration error at superior (1.7 +/- 0.7 mm), inferior (2.2 +/- 1.4 mm), septal (1.7 +/- 0.8 mm), and lateral (1.7 +/- 0.7 mm, P = 0.13) sites. Cardiac rhythm at the time of CT did not have a significant effect on total or regional surface registration accuracy (mean total 2.5 +/- 0.3 in AF patients vs 2.3 +/- 0.5 in SR patients, P = 0.22). The integrated CT was used to guide the encirclement of the pulmonary veins (PV) in pairs with electrical isolation achieved by maintaining ablation along the ablation line in 58 of 60 PV pairs. Postprocedural PV angiography did not demonstrate significant stenosis. CONCLUSION: CT image integration into an EAM system was successfully performed in patients undergoing catheter ablation for AF. With a greater appreciation of the complex and variable nature of the PV and LA anatomy this new technology may improve the efficacy and safety of the procedure.

Atrial Fibrillation↗
PubMed2006

The impact of CT image integration into an electroanatomic mapping system on clinical outcomes of catheter ablation of atrial fibrillation.

BACKGROUND: A detailed appreciation of left atrial/pulmonary vein (LA/PV) anatomy may be important in improving the safety and success of catheter ablation (CA) for atrial fibrillation (AF). OBJECTIVES: The aim of this nonrandomized study was to determine the impact of computerized tomography (CT) image integration into a 3-dimensional (3D) mapping system on the clinical outcome of patients undergoing CA for AF. METHODS: Ninety-four patients (age: 56 +/- 10 years) with AF (paroxysmal 46, persistent 48) underwent wide encirclement of ipsilateral PV pairs using irrigated radiofrequency ablation with the endpoint of electrical isolation. Ablation was guided by 3D mapping alone (electroanatomic 24, noncontact 23) in 47 (3DM group) patients and by CT image integration (Cartomerge) in 47 (CT group). In persistent AF, a combination of linear ablation and targeted ablation of complex fractionated electrograms was also performed. RESULTS: Successful PV electrical isolation did not differ between the two groups. A significant reduction in fluoroscopy times was demonstrated in the CT group (49 +/- 27 minutes vs 3DM group 62 +/- 26 minutes, P = 0.03). Arrhythmia recurrence was reduced in the CT group (32% vs 51% in the 3DM group, P < 0.01). In 30 symptomatic patients (12 CT and 18 3DM), repeat procedures for AF (13 in 3DM and 5 CT, P < or = 0.10) and AT (5 in 3DM and 7 CT, P = NS) were performed. Overall success on 7-day monitor off antiarrhythmic drugs was achieved in 60% in the 3DM group when compared with 83% in the CT group (P < 0.05) at a follow-up of 25 +/- 5 weeks. CONCLUSION: CA for AF guided by CT integration was associated with reduced fluoroscopy times, arrhythmia recurrence, and increased restoration of sinus rhythm. Improved visualization of complex LA geometries might improve the safety and success of CA for AF.

Atrial Fibrillation↗
PubMed2006

An overview of the TAXUS Express, paclitaxel-eluting stent clinical trial program.

Restenosis remains a problem following percutaneous coronary intervention in patients with coronary artery disease. Drug-eluting stents (DES), which combine mechanical and pharmacologic properties, have been shown to prevent or reduce neointimal growth after deployment. This review describes the TAXUS paclitaxel-eluting stent clinical trial expansion program (TAXUS Express, Boston Scientific, Natick, MA). This program comprises the largest data set of randomized controlled trials (RCTs) of DES to date, with over 6,200 patients enrolled since 2000. The program includes treatment of de novo lesions, as well as higher-risk lesion and patient populations. In this review, we discuss the results from the TAXUS family of randomized clinical trials, and compare the findings with data from TAXUS registries. The data from the randomized clinical trials suggest that the paclitaxel-eluting stent provides consistent and durable benefits across multiple lesion and patient types. Evidence from peri-and post-approval registries, where patient populations are more heterogeneous than those eligible and included in the RCTs, corroborate these findings, with overall low rates of cardiac events, including reinterventions.

Angioplasty, Balloon, Coronary↗
PubMed2005

Creation of a large-scale genetic data bank for cardiovascular association studies.

BACKGROUND: A prerequisite for undertaking genetic association studies is the need for a genetic data bank with adequate DNA samples and a well-described clinical cohort. METHODS: We initiated a prospective single-center study enrolling 6,273 patients referred for cardiac catheterization in a genetic data bank (with eventual goal of 10,000 enrollees). Using a prescreening tool, the patients had comprehensive clinical phenotyping, including angiogram, electrocardiogram, echocardiogram, clinical history, and medication profile (Appendix A). Along with this clinical information, DNA, serum, plasma, basic metabolic panel, inflammation, and lipid panel were collected and stored in the database. RESULTS: Mean age of the patients enrolled was 64 +/- 12 years; 69% are men, 26% have diabetes, 79% have dyslipidemia, and 72% have coronary artery disease (CAD) > or = 50%. We undertook extensive quality-control measures to ensure the validity of both the clinical and DNA samples acquired into our GenBank. As part of this validation, we undertook a genetic association study to discern the effect of the apoE4 polymorphism on the risk for atherosclerosis. We are able to show that the apoE4 polymorphism is an independent risk factor for CAD. CONCLUSIONS: We have been able to create a large-scale genetic data bank as a resource to undertake genetic association studies. Key elements in implementation of this GenBank and baseline characteristics of our patient cohort are summarized. Lastly, as a "proof of concept" for the utility of this resource to discern gene variants associated with disease, we validated apoE4 polymorphism as an independent risk factor for CAD.

Aged↗
PubMed2005

LightTyper platform for high-throughput clinical genotyping.

DNA sequence variations due to single nucleotide changes or polymorphisms (SNPs) have demonstrated an association with certain diseases as causative agents or surrogate biomarkers. Identification and genotyping of SNPs requires reliable and robust technologies. Multiple genotyping platforms are available to detect SNPs. Although many of these platforms meet the requirements of the research environment, technologies have also emerged for high-throughput clinical genotyping as well. The LightTyper is one such platform, providing SNP identification by employing melting curve analysis of fluorescently labeled probes. The LightTyper has been used to identify SNPs associated with myocardial infarction, developing and validating assays for approximately 100 SNPs in 30 candidate genes. The LightTyper is also amenable to the use of assays already developed for the LightCycler, which is widely used in clinical laboratories. The initial experience presented here suggests the potential use of the LightTyper for high-throughput clinical genotyping.

Animals↗
PubMed2003

[Prostate cancer and quality of life].

Faced with equivalent treatments in terms of control of localised prostate cancer, by treatments as different as radical prostectomy and radiotherapy, the analysis of the physical and psychosocial consequences of each treatment is indispensable in determining the therapeutic options proposed to a patient. Current information on the quality of life after treatment of localised and metastatic prostate cancer show effects after treatment that are specific to this pathology (urinary, sexual and digestive problems) and general (physical state and functional capacity, capacity to accomplish all forms of work, capacity to maintain social relations...). These effects nevertheless differ depending of the stage of the disease and the type of treatment.

Brachytherapy↗
PubMed2003

Identification of new genes differentially expressed in coronary artery disease by expression profiling.

Genetic factors increase the risk to coronary artery disease (CAD). To date, a limited number of genes that potentially contribute to development of CAD have been identified. In this study, we have performed large-scale gene expression analysis of approximately 12,000 human genes in nine severely atherosclerotic and six nonatherosclerotic human coronary arteries using oligonucleotide microarrays. Fifty-six genes showed differential expression in atherosclerotic coronary artery tissues; expression of 55 genes was increased in atherosclerotic coronary arteries, whereas only one gene, GST, encoding a reducing agent, showed downregulated expression. The expression data of selected genes were validated by quantitative RT-PCR analysis as well as immunostaining. The associations of 49 genes with CAD appear to be novel, and they include genes encoding ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, beta2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-alpha-induced protein 2 (B94), and flavocytochrome 558. In conclusion, we have identified 56 genes whose expression is associated with CAD, and 49 of them may represent new genes linked to CAD.

Apoptosis↗
PubMed2002

Long-term outcome of patients treated with repeat percutaneous coronary intervention after failure of gamma-brachytherapy for the treatment of in-stent restenosis.

BACKGROUND: Although (192)Ir intracoronary brachytherapy has been demonstrated to dramatically reduce the recurrence of in-stent restenosis, up to 24% of these patients will still require repeat target-vessel revascularization. The short- and long-term outcomes of repeat percutaneous intervention in this population have not been characterized. METHODS AND RESULTS: Analysis was performed of all patients enrolled in the GAMMA-I and GAMMA-II brachytherapy trials who underwent repeat percutaneous target lesion revascularization (TLR) because of restenosis. Subjects were divided into 2 cohorts: those who had received (192)Ir brachytherapy and those randomized to placebo. Forty-five (17.6%) of a total of 256 patients whose index treatment was intracoronary radiation therapy and 36 (29.8%) of 121 patients whose index treatment was placebo required repeat percutaneous TLR. The mean time to this first TLR was 295+/-206 days in the irradiated group and 202+/-167 days in the placebo group (P=0.03). Acute procedural success occurred in 100% of irradiated patients and 94% of placebo controls (P=0.19). After the first TLR, a subsequent TLR was required in 15 (33.3%) of 45 brachytherapy patients versus 17 (47.2%) of 36 placebo failure patients (P=0.26). There was no significant difference in time to second TLR between the 2 groups. Other long-term major adverse event rates in both groups were comparable to those of other contemporary angioplasty/stenting series. CONCLUSIONS: In those patients who "fail" (192)Ir intracoronary brachytherapy for in-stent restenosis, treatment with (192)Ir delays the time to first TLR. Additionally, repeat percutaneous intervention in these patients is safe and efficacious in the short term, with acceptable long-term results.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): exposure and toxicokinetics prior to and during pregnancy.

Toxicokinetic studies were conducted following daily inhalation exposure to methanol vapor prior to and throughout pregnancy in adult female Macaca fascicularis monkeys. They were part of a larger study to investigate the effects of chronic methanol exposure on maternal reproductive performance and early offspring effects. In a two-cohort study design, 48 females (24/cohort) were assigned to parallel exposure groups at 0 (control), 200, 600, or 1800 ppm methanol vapor for approximately 2.5 h/day, 7 days/week throughout breeding and pregnancy. Blood methanol at 30 min postexposure was monitored biweekly. The time course for the clearance of blood MeOH concentrations following exposure was characterized on four occasions: twice during the prebreeding period and during mid- and late pregnancy. Average blood methanol concentrations at 30 min postexposure were 5, 11, and 35 microg/ml across all four toxicokinetic studies in the 200, 600 and 1800 ppm groups, respectively. Blood concentrations in the 200 ppm group were barely above basal (preexposure) blood methanol concentrations or those observed in the control group (approximately 3 microg/ml). Nonlinear elimination kinetics were observed in most of the 1800 ppm group females. There was a decrease in elimination half-life (7-20%) and an increase in clearance (30%) after 3-months of daily MeOH exposure compared to the initial exposure. There were no statistically significant changes in the first-order blood methanol half-life or clearance during pregnancy, but the mean distribution volume per kilogram body weight decreased by 22% and 17% in the 600 and 1800 ppm groups. Plasma formate levels did not differ between the methanol and control exposure groups. Plasma formate and serum folate concentrations increased slightly over the course of this study in both the exposed and control groups but these increases were not related to methanol exposure.

Administration, Inhalation↗
PubMedDate not supplied

Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): reproductive performance and birth outcome.

The present study was designed to characterize maternal reproductive performance and early offspring effects following exposure to methanol (MeOH) vapor in a nonhuman primate model. The two-cohort study design used 48 adult female Macaca fascicularis (24/cohort) monkeys exposed to 0, 200, 600, or 1800 ppm MeOH vapor for approximately 2.5 h/day, 7 days/week prior to breeding and throughout pregnancy. Maternal body weight measurement, clinical observations and health assessments were conducted routinely throughout the study. Menstrual cyclicity was monitored during the pre-breeding and breeding periods and timed matings were conducted with nonexposed males. Females were monitored closely during the last month of pregnancy. At birth, infant physical characteristics were measured and a newborn health assessment was conducted. Methanol exposure did not alter menstrual cycles, the number of breedings to conception or conception rate. A total of 34 live-born infants were delivered (control=8, 200 ppm=9, 600 ppm=8, 1800 ppm=9). One female each in the control and 600-ppm group delivered a stillborn infant and a cesarean section (C-section) was required to deliver a hydrocephalic infant who died in utero in the maternal 1800-ppm group. Although not statistically significant, five MeOH-exposed females were C-sectioned due to pregnancy complications such as uterine bleeding and prolonged unproductive labor. These complications were not observed in the control group. The mean length of pregnancy in the MeOH-exposed groups was significantly decreased by 6 to 8 days when compared to controls. There were no MeOH-related effects on offspring birthweight or newborn health status. The consistent reduction in length of pregnancy observed in the MeOH females may reflect a treatment effect on the fetal neuroendocrine system. Given that the fetal hypothalamic--pituitary-adrenal axis controls pregnancy length in most species, these results suggest a modest but significant effect of MeOH on the biochemical events that control the timing of birth.

Administration, Inhalation↗