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Biomedical subjects

David Holmes

Publications and source records attributed to David Holmes.

At least 19 recordsLinked to original sources
PubMed2007

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. OBJECTIVE: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. DESIGN, SETTING, AND PATIENTS: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. INTERVENTIONS: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. MAIN OUTCOME MEASURES: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. RESULTS: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). CONCLUSION: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00091637.

Aged↗
PubMed2006

Generation and analysis of expressed sequence tags from Botrytis cinerea.

Botrytis cinerea is a filamentous plant pathogen of a wide range of plant species, and its infection may cause enormous damage both during plant growth and in the post-harvest phase. We have constructed a cDNA library from an isolate of B. cinerea and have sequenced 11,482 expressed sequence tags that were assembled into 1,003 contigs sequences and 3,032 singletons. Approximately 81% of the unigenes showed significant similarity to genes coding for proteins with known functions: more than 50% of the sequences code for genes involved in cellular metabolism, 12% for transport of metabolites, and approximately 10% for cellular organization. Other functional categories include responses to biotic and abiotic stimuli, cell communication, cell homeostasis, and cell development. We carried out pair-wise comparisons with fungal databases to determine the B. cinerea unisequence set with relevant similarity to genes in other fungal pathogenic counterparts. Among the 4,035 non-redundant B. cinerea unigenes, 1,338 (23%) have significant homology with Fusarium verticillioides unigenes. Similar values were obtained for Saccharomyces cerevisiae and Aspergillus nidulans (22% and 24%, respectively). The lower percentages of homology were with Magnaporthe grisae and Neurospora crassa (13% and 19%, respectively). Several genes involved in putative and known fungal virulence and general pathogenicity were identified. The results provide important information for future research on this fungal pathogen.

Botrytis↗
PubMed2006

Psychophysiologic responses of invasive cardiologists in an academic catheterization laboratory.

BACKGROUND: This study examined the psychophysiologic responses of invasive cardiologists during cardiac catheterizations. Because occupations are most stressful when one is not in control, the effect of a teaching versus an autonomous role on the psychophysiologic response of invasive cardiologists was investigated. METHODS: The subjects were 9 invasive cardiologists. Psychophysiologic variables such as state anxiety and salivary cortisol levels were measured before and after each invasive cardiologist performed 7 cardiac catheterizations. Heart rate was measured before, during, and after procedures. Three procedures were studied while invasive cardiologists were in the primary operator (autonomous) role with full responsibility and control, whereas 4 were studied while the subjects were in the secondary assistant (teaching) role with full responsibility and no control. RESULTS: There were no significant differences in physiologic arousal (heart rate and salivary cortisol levels) between catheterizations performed in the autonomous role versus those in the teaching role. However, the perceived anxiety scores were higher when in the teaching role versus when in the autonomous role. There were significant differences in psychophysiologic measurements of stress between less experienced cardiologists (out of training < 5 years) and more experienced cardiologists (out of training > 5 years). Less experienced invasive cardiologists had significantly higher trait anxiety (38.4 vs 31.7, P = .001), baseline salivary cortisol levels (0.51 vs 0.33, P = .01), and heart rate change (50.1 vs 27.4 beats/min, P = .001) during procedures compared with more experienced cardiologists. CONCLUSIONS: Although there were no overall differences in the physiologic response to the autonomous and teaching roles, there was a higher perceived state of anxiety when in the teaching role. Less experienced invasive cardiologists had higher psychophysiologic measurements of stress during invasive procedures than did more experienced cardiologists.

Adult↗
PubMed2006

Inactivation of a two-component signal transduction system, SaeRS, eliminates adherence and attenuates virulence of Staphylococcus aureus.

Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding alpha-, beta-, and gamma-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells.

Animals↗
PubMed2006

Phylogenomic and biochemical characterization of three Legionella pneumophila polypeptide deformylases.

Legionella pneumophila is a gram-negative facultative intracellular human pathogen that can cause fatal Legionnaires' disease. Polypeptide deformylase (PDF) is a novel broad-spectrum antibacterial target, and reports of inhibitors of PDF with potent activities against L. pneumophila have been published previously. Here, we report the identification of not one but three putative pdf genes, pdfA, pdfB, and pdfC, in the complete genome sequences of three strains of L. pneumophila. Phylogenetic analysis showed that L. pneumophila PdfA is most closely related to the commonly known gamma-proteobacterial PDFs encoded by the gene def. PdfB and PdfC are more divergent and do not cluster with any specific bacterial or eukaryotic PDF. All three putative pdf genes from L. pneumophila strain Philadelphia 1 have been cloned, and their encoded products have been overexpressed in Escherichia coli and purified. Enzymatic characterization shows that the purified PDFs with Ni2+ substituted are catalytically active and able to remove the N-formyl group from several synthetic polypeptides, although they appear to have different substrate specificities. Surprisingly, while PdfA and PdfB with Zn2+ substituted are much less active than the Ni2+ forms of each enzyme, PdfC with Zn2+ substituted was as active as the Ni2+ form for the fMA substrate and exhibited substrate specificity different from that of Ni2+ PdfC. Furthermore, the catalytic activities of these enzymes are potently inhibited by a known small-molecule PDF inhibitor, BB-3497, which also inhibits the extracellular growth of L. pneumophila. These results indicate that even though L. pneumophila has three PDFs, they can be effectively inhibited by PDF inhibitors which can, therefore, have potent anti-L. pneumophila activity.

Amidohydrolases↗
PubMed2005

High throughput particle analysis: combining dielectrophoretic particle focussing with confocal optical detection.

A micro flow cytometer has been fabricated that detects and counts fluorescent particles flowing through a microchannel at high speed based upon their fluorescence emission intensity. Dielectrophoresis is used to continuously focus particles within the flowing fluid stream into the centre of the device, which is 40 microm high and 250 microm wide. The method ensures that all the particles pass through an interrogation region approximately 5 microm in diameter, which is created by focusing a beam of light into a spot. The functioning of the device was demonstrated by detecting and counting fluorescent latex particles at a rate of up to 250 particles/s. A mixture of three different populations of latex particle was used, each sub-population with a distinct level of fluorescent intensity. The device was evaluated by comparison with a conventional fluorescent activated cell sorter (FACS) and numerical simulation demonstrated that for 6 microm beads, and for this design of chip the theoretical throughput is of the order of 1000 particles/s (corresponding to a particle velocity of 10 mm s(-1)).

Biosensing Techniques↗
PubMed2005

Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure.

The resistance of tissues to physical stress is dependent upon strong cell-cell adhesion in which desmosomes play a crucial role. We propose that desmosomes fulfil this function by adopting a more strongly adhesive state, hyper-adhesion, than other junctions. We show that the hyper-adhesive desmosomes in epidermis resist disruption by ethylene glycol bis(2-aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA) and are thus independent of Ca2+. We propose that Ca2+ independence is the normal condition for tissue desmosomes. Ca2+ independence is associated with an organised arrangement of the intercellular adhesive material exemplified by a dense midline. When epidermis is wounded, desmosomes in the wound-edge epithelium lose hyper-adhesiveness and become Ca2+ dependent, i.e. readily dissociated by EGTA. Ca2+-dependent desmosomes lack a midline and show narrowing of the intercellular space. We suggest that this indicates a less-organised, weakly adhesive arrangement of the desmosomal cadherins, resembling classical cadherins in adherens junctions. Transition to Ca2+ dependence on wounding is accompanied by relocalisation of protein kinase C alpha to desmosomal plaques suggesting that an 'inside-out' transmembrane signal is responsible for changing desmosomal adhesiveness. We model hyper-adhesive desmosomes using the crystal packing observed for the ectodomain of C-cadherin and show how the regularity of this 3D array provides a possible explanation for Ca2+ independence.

Animals↗
PubMed2005

Global regulation of gene expression by ArlRS, a two-component signal transduction regulatory system of Staphylococcus aureus.

Staphylococcus aureus expresses various cell wall-associated and extracellular virulence factors, coordinately controlled by different two-component signal transduction systems and transcriptional regulators. In this study, we used microarray technology to identify the genes regulated by ArlR. The microarray data indicate that ArlR functions as a positive regulator and also as a negative repressor to directly and/or indirectly mediate the expression of at least 114 genes involved in different functions, including autolysis, cell division, growth, and pathogenesis.

Bacterial Proteins↗
PubMed2004

Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor.

The androgen receptor (AR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and plays a key role in the development and progression of prostate cancer. Current therapies include the use of antiandrogens aimed at inhibiting the transcriptional activation of AR-regulated genes by AR. Here, we explore a strategy aimed at obtaining silencing of AR-regulated genes, based on the properties of the transcriptional repressor promyelocytic leukamia zinc-finger protein (PLZF). In order to do this, we have made a fusion protein between PLZF and AR, named PLZF-AR, and show that PLZF-AR is able to bring about silencing of genomically encoded AR-regulated genes and inhibit the androgen-regulated growth of LNCaP prostate cancer cells. Together, our results show that this strategy is able to bring about potent repression of AR-regulated responses and, therefore, could be of value in the development of new therapies for prostate cancer.

Androgens↗
PubMed2004

Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes.

The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 (GLP-1) is not established. Here, the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 (DPP-4) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [age: 65 +/- 8 yr (SD), body mass index: 27.3 +/- 3.3 kg/m(2), fasting plasma glucose: 9.0 +/- 1.3 mmol/liter]. Compared with placebo (n = 19), a specific DPP-4 inhibitor [(1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine) (LAF237); 100 mg daily, n = 18] reduced fasting glucose by 0.70 mmol/liter (P = 0.037), 4-h prandial glucose excursion by 1.45 mmol/liter (P < 0.001), and mean 24-h glucose by 0.93 mmol/liter (P < 0.001). Baseline and postprandial active GLP-1 were increased by LAF237. The glucagon response to breakfast was reduced by LAF237 (glucagon levels at 60 min were 88 +/- 8 pg/ml before treatment vs. 77 +/- 5 pg/ml after; P = 0.001). In contrast, the overall insulin levels were not altered. The 4-wk reduction in glucagon correlated with the reduction in 2-h glucose (r = 0.61; P = 0.008). No such association was observed for insulin. Thus, improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels.

Adamantane↗
PubMed2004

Rationale and study design of the CardioGene Study: genomics of in-stent restenosis.

BACKGROUND AND AIMS: in-stent restenosis is a major limitation of stent therapy for atherosclerosis coronary artery disease. The CardioGene Study is an ongoing study of restenosis in bare mental stents (BMS) for the treatment of coronary artery disease. The overall goal is to understand the genetic determinants of the responses to vascular injury that result in the development of restenosis in some patients but not in others. Gene expression profiling at transcriptional and translational levels provides global assessment of gene activity after vascular injury and mechanistic insight. Furthermore, the delineation of genetic biomarkers would be of value in the clinical setting of risk-stratify patients prior to stent therapy. Prospective risk stratification would allow for the rational selection of specialized treatments against the development of in-stent restenosis (ISR), such as drug-eluting stents. SETTING: Patients are enrolled at two sites in the US with high-volume cardiac catheterization facilities: the William Beaumont Hospital in Royal Oak, MI, USA, and the Mayo Clinic in Rochester, MN, USA. STUDY DESIGN: Two complementary study designs are used to understand the molecular mechanisms of restenosis and the genetic biomarkers predictive of restenosis. First, 350 patients are enrolled prospectively at the time of stent implantation. Blood is sampled prior to stent placement and afterwards at 2 weeks and 6 months. The clinical outcome of restenosis is determined 6 and 12 months after stent placement. The primary outcome is clinical restenosis at 6 months. The major secondary outcome is clinical restenosis at 12 months. Second, a corollary case-control analysis will be carried out with the enrollment of an additional 250 cases with a history of recurrent restenosis after treatment with BMS. Controls for this analysis are derived from the prospective cohort. PATIENTS AND METHODS: Consecutive patients presenting to the cardiac catheterization laboratory are screened, informed about the study and enrolled after signing the consent form. Enrollment has been completed for the prospective cohort, and enrollment of the additional group is ongoing. A standardized questionnaire is used to collect clinical data primarily through direct patient interview to assess medical history, medication use, functional status, family history, environmental factors, and social history. Further data are abstracted from the medical charts and catheterization reports. A total of 276 clinical variables are collected per individual at baseline, and 49 variables are collected at each of the 6- and 12-month follow-up visits. A Clinical Events Committee adjudicates clinical outcomes. Blood samples are processed at each clinical enrollment site using standardized operating procedures. From each blood sample, several aliquots are prepared and stored of peripheral blood mononuclear cells, granulocytes, platelets, serum, and plasma. Additionally, a portion of each patient's leukocytes is cryopreserved for future cell-line creation. Samples are frozen and shipped to the National Heart, Lung and Blood Institute (NHLBI). Additional materials generated in the analysis of the samples at the NHLBI are frozen and stored, including isolated genomic DNA, total RNA, reverse transcribed cDNA libraries and labeled RNA hybridization mixtures used in microarray analysis. Per individual in the prospective cohort, high-quality transcript profiles of peripheral blood mononuclear cells at each time of blood sampling are obtained using Affymetrix U133A microarrays (Affymetrix, Santa Clara, CA, USA). Per chip, this yields 495,930 features per individual per time of sampling. This represents expression levels for 22,283 genes per patients oer time of blood sampling, including 14,500 well-characterized human genes. Proteomics of plasma is performed with multidimensional liquid chromatography and tandem mass spectrometry. Protein expression is examined similarly to mRNA expression as a measure of gene expression. Genotyping is performed in two manners. First, those genes showing differential expression at the levels of mRNA and protein are investigated using a candidate gene approach. Specific variants in known gene regulatory regions, such as promoters, are sought initially, as those variants may explain differences in expression level. Second, a genome-wide scan is used to identify genetic loci that are associated with ISR. Those regions identified are further examined for genes that show differential expression in the mRNA microarray profiling or proteomics investigations. These genes are finely investigated for candidate SNPs and other gene variants. Complementary genomic and proteomic approaches are expected to be robust. Integration of data sets is accomplished using a variety of informatics tools, organization of gene expression into functional pathways, and investigation of physical maps of up- and downregulated sets of genes. CONCLUSIONS: The CardioGene Study is designed to understand ISR. Global gene and protein expression profiling define molecular phenotypes of patients. Well-defined clinical phenotypes will be paired with genomic data to define analyses aimed to achieve several goals. These include determining blood gene and protein expression in patients with ISR, investigating the genetic basis of ISR, developing predictive gene and protein biomarkers, and the identification of new targets for treatment.

Clinical Trials as Topic↗
PubMed2004

Coronary pressure notch: an early non-hyperemic visual indicator of the physiologic significance of a coronary artery stenosis.

The disappearance of a dichrotic notch on the peripheral arterial pulse wave has been associated with significant peripheral vascular disease. A similar observation has not been reported in the distal coronary pressure waveform. The purpose of this study was to investigate the significance of a coronary pressure notch distal to a coronary stenosis and its relationship to fractional flow reserve. Ninety-seven patients with 131 angiographically indeterminate lesions (40-80% diameter narrowing) underwent FFR measurements for physiological significance. Hemodynamic tracings were recorded prior to the administration of adenosine and visually analyzed for the presence or absence of a dicrotic notch in the distal coronary artery pressure tracing. The stenoses were then divided into two groups based on the presence or absence of a notch. Of the 54 lesions without a distal coronary pressure notch, 31 had a FFR greater than or equal to 0.75 and of the 77 lesions with a notch, 75 had a FFR greater than or equal to 0.76. The sensitivity and specificity of a pressure notch was 94% and 74%, respectively, with positive and negative predictive values of 57% and 97%, respectively. The presence of a distal coronary pressure notch was predictive of a FFR greater than or equal to 0.76. The distal dicrotic pressure notch may be used as an additional parameter without requiring hyperemia for FFR measurements of uncertain clinical significance.

Age Factors↗
PubMed2003

Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis.

BACKGROUND: Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. RESULTS: Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. CONCLUSIONS: A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis.

Adenosine Phosphosulfate↗
PubMed2003

Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of noncardiac origin are enriched in transplant atherosclerosis.

BACKGROUND: Recent studies in animals suggest that circulating recipient endothelial precursors may participate in the biology of transplant vasculopathy. It is currently unknown whether a similar interaction between recipient endothelial cells and the vessel wall occurs in human subjects undergoing allogeneic cardiac transplantation. METHODS AND RESULTS: Circulating endothelial cells and endothelial progenitor cells (EPCs) were quantified in 15 cardiac transplantation subjects with and without angiographic evidence of vasculopathy. In a separate series of experiments, the origin (donor or recipient) of transplant plaque endothelial cells was assessed in subjects who had undergone a gender-mismatched cardiac transplantation and had histological evidence of severe vasculopathy at the time of heart explantation. Circulating EPC outgrowth colonies in peripheral blood were significantly reduced in subjects with transplant vasculopathy compared with those without angiographic evidence of disease (EPC colony-forming units [CFUEPC]: 4.5+/-1.9 versus 15.1+/-3.7, P<0.05). There was no significant difference in circulating endothelial cell numbers as defined by day 4 culture acetylated LDL/lectin assay in either of these patient groups. In a separate group of 5 subjects who underwent gender-mismatched cardiac transplantation, there was a significant seeding of recipient endothelial cells (range: 1% to 24% of all luminal endothelial cells) in large-vessel lumen and adventitial microvessel lumen of arteriopathic vessels. No opposite-sex chimeric cells were observed in control gender-matched transplantation scenarios. CONCLUSIONS: These data suggest that the human cardiac transplant arteriopathy is associated with reduction in circulating endothelial precursors and with seeding of recipient-derived endothelial cells at the site of plaque development.

Adult↗
PubMed2003

Rationale and design of the randomized, multicenter, cilostazol for RESTenosis (CREST) trial.

Restenosis of a segment of diseased coronary artery following metallic stenting is a common clinical problem and a major limitation of the procedure. Systemic pharmacologic interventions to deal with this problem have met with little success. Several small studies suggest that cilostazol, a phosphodiesterase III inhibitor whose pharmacologic properties include antiplatelet, antithrombotic, and vasodilatory effects; a beneficial effect on serum lipids; and in vitro inhibition of smooth muscle cell proliferation, may help prevent platelet aggregation and impede the accumulation of new intimal tissue in the stented artery. The Cilostazol for RESTenosis (CREST) trial will aim to evaluate more definitively the ability of cilostazol to prevent restenosis following uncomplicated stent implantation for de novo coronary artery stenosis. In this randomized, double-blind, multicenter study, 700 patients will receive clopidogrel, aspirin, and either cilostazol or placebo after successful intracoronary stent implantation. The primary endpoint is minimal luminal diameter (MLD) of the first lesion stented after 6 months; secondary endpoints include MLD in all lesions, mean percent diameter stenosis, target lesion revascularization, and major angiographic endpoints. Safety endpoints are abnormal complete blood count and liver function tests at 1, 3, and 6 months. The trial has been initiated, and enrollment is anticipated to be concluded in 2003. Cilostazol has properties that may reduce or avert in-stent coronary restenosis. The CREST trial is a large, rigorously conducted trial that may corroborate the favorable effects of cilostazol on coronary stent restenosis suggested by earlier studies.

Adolescent↗