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L Elliot Hong,Matthew T Avila,Helene Adami,Amie Elliot,Gunvant K Thaker The diagnosis of schizophrenia likely encompasses a heterogeneous group of disorders, complicating the search for its causes. Studies of deficit schizophrenia represent an attempt to reduce this heterogeneity by identifying biologically distinct subgroups. Supplementing clinical phenotypes with bio... ( view more )logical markers of risk (e.g., eye-tracking and sensory-gating deficits) have also been used to reduce disease heterogeneity. In this study, we examined smooth pursuit eye movements in healthy controls (n = 37), and deficit (n = 18) and nondeficit (n = 32) patients with schizophrenia to determine what aspects of abnormal smooth pursuit are associated with the two patient groups, and which, if any, specifically mark the deficit phenotype. A small sample of relatives of deficit (n = 12) and nondeficit (n = 35) patients was also examined. Positive symptoms were equally present in deficit and nondeficit patients. Subtle, psychotic-like positive traits were also equally present in the relatives of both deficit and nondeficit probands, whereas negative symptoms were significantly more prevalent among the relatives of deficit probands. Deficits in predictive pursuit were present in both patient groups and both groups of relatives. Deficit patients showed significantly lower initiation acceleration. A similar pattern of results was seen in our pilot sample of relatives of deficit patients. These findings suggest that predictive smooth pursuit abnormality is associated with positive symptoms in schizophrenia, and that initiation abnormalities may be associated with the deficit syndrome. ( view less ) E Lupia,S J Elliot,O Lenz,F Zheng,M Hattori,G E Striker,L J Striker Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ... ( view more ), Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis. ( view less ) Zhiliang Xu,Nan Chen,Malgorzata M Kamocka,Elliot D Rosen,Mark Alber A two-dimensional multiscale model is introduced for studying formation of a thrombus (clot) in a blood vessel. It involves components for modelling viscous, incompressible blood plasma; non-activated and activated platelets; blood cells; activating chemicals; fibrinogen; and vessel walls and their... ( view more ) interactions. The macroscale dynamics of the blood flow is described by the continuum Navier-Stokes equations. The microscale interactions between the activated platelets, the platelets and fibrinogen and the platelets and vessel wall are described through an extended stochastic discrete cellular Potts model. The model is tested for robustness with respect to fluctuations of basic parameters. Simulation results demonstrate the development of an inhomogeneous internal structure of the thrombus, which is confirmed by the preliminary experimental data. We also make predictions about different stages in thrombus development, which can be tested experimentally and suggest specific experiments. Lastly, we demonstrate that the dependence of the thrombus size on the blood flow rate in simulations is close to the one observed experimentally. ( view less ) D M Fleming,A J Elliot SUMMARYThe influenza virus continues to pose a significant threat to public health throughout the world. Current avian influenza outbreaks in humans have heightened the need for improved surveillance and planning. Despite recent advances in the development of vaccines and antiviral drugs, seasonal ... ( view more )epidemics of influenza continue to contribute significantly to general practitioner workloads, emergency hospital admissions, and deaths. In this paper we review data produced by the Royal College of General Practitioners Weekly Returns Service, a sentinel general practice surveillance network that has been in operation for over 40 years in England and Wales. We show a gradually decreasing trend in the incidence of respiratory illness associated with influenza virus infection (influenza-like illness; ILI) over the 40 years and speculate that there are limits to how far an existing virus can drift and yet produce substantial new epidemics. The burden of disease caused by influenza presented to general practitioners varies considerably by age in each winter. In the pandemic winter of 1969/70 persons of working age were most severely affected; in the serious influenza epidemic of 1989/90 children were particularly affected; in the millennium winter (in which the NHS was severely stretched) ILI was almost confined to adults, especially the elderly. Serious confounders from infections due to respiratory syncytial virus are discussed, especially in relation to assessing influenza vaccine effectiveness. Increasing pressure on hospitals during epidemic periods are shown and are attributed to changing patterns of health-care delivery. ( view less ) Frank M Corl,Pamela T Johnson,Melissa R Rowell,Elliot K FishmanOBJECTIVE: Video "podcasting" is an Internet-based publication and syndication technology that is defined as the process of capturing, editing, distributing, and downloading audio, video, and general multimedia productions. The expanded capacity for visual components allows radiologists to view sti... ( view more )ll and animated media. CONCLUSION: These image-viewing characteristics and the ease of widespread delivery are well suited for radiologic education. This article presents detailed information about how to generate and distribute a video podcast using a Macintosh platform. ( view less ) Britta Hahn,Frank A Wolkenberg,Thomas J Ross,Carol S Myers,Stephen J Heishman,Dan J Stein,Pradeep K Kurup,Elliot A Stein The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often ... ( view more )been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention. ( view less ) Susan L Christian,Camille W Brune,Jyotsna Sudi,Ravinesh A Kumar,Shaung Liu,Samer Karamohamed,Judith A Badner,Seiichi Matsui,Jeffrey Conroy,Devin McQuaid,James Gergel,Eli Hatchwell,T Conrad Gilliam,Elliot S Gershon,Norma J Nowak,William B Dobyns,Edwin H Cook BACKGROUND: One genetic mechanism known to be associated with autism spectrum disorders (ASD) is chromosomal abnormalities. The identification of copy number variants (CNV), i.e., microdeletions and microduplications that are undetectable at the level of traditional cytogenetic analysis, allows the... ( view more ) potential association of submicroscopic chromosomal imbalances and human disease. METHODS: We performed array comparative genomic hybridization (aCGH) utilizing a 19K whole genome tiling path bacterial artificial chromosome (BAC) microarray on 397 unrelated subjects with autism spectrum disorder. Common CNV were excluded using a control group comprised of 372 individuals from the National Institute of Mental Health (NIMH) Genetics Initiative Control samples. Confirmation studies were performed on all remaining CNV using fluorescence in situ hybridization (FISH), microsatellite analysis, and/or quantitative polymerase chain reaction (PCR) analysis. RESULTS: A total of 51 CNV were confirmed in 46 ASD subjects. Three maternal interstitial duplications of 15q11-q13 known to be associated with ASD were identified. The other 48 CNV ranged in size from 189 kilobase (kb) to 5.5 megabase (Mb) and contained from 0 to approximately 40 National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) genes. Seven CNV were de novo and 44 were inherited. CONCLUSIONS: Fifty-one autism-specific CNV were identified in 46 of 397 ASD patients using a 19K BAC microarray for an overall rate of 11.6%. These microdeletions and microduplications cause gene dosage imbalance in 272 genes, many of which could be considered as candidate genes for autism. ( view less ) Kimberly R Kalli,Christopher J Krco,Lynn C Hartmann,Karin Goodman,Matthew J Maurer,Chao Yu,Elliot M Johnson,Courtney L Erskine,Mary L Disis,Peter J Wettstein,John D Fikes,Melanie Beebe,Glenn Ishioka,Keith L Knutson Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I-based vaccines. In this study, the goal was to identify an HLA-DR-dege... ( view more )nerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2). IGFBP-2, a regulator of insulin-like growth factor action, is overexpressed in the majority of breast and ovarian cancers. Using algorithms, we predicted 29 HLA-DR1-binding epitopes. Binding assays targeting 15 different HLA-DRs revealed that 10 epitopes were degenerate, binding to at least four different HLA-DR variants. An IFN-gamma enzyme-linked immunosorbent spot assay was used to assess immunity to these 10 epitopes in 48 patients with either breast or ovarian cancer and 18 controls. Elevated T-cell immunity in patients was detected in 4 of the 10 epitopes (IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293). The cumulative T-cell frequency of these four epitopes was elevated in patients relative to controls. All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization. ( view less ) Alan M Jones,Joanne Chory,Jeffery L Dangl,Mark Estelle,Steven E Jacobsen,Elliot M Meyerowitz,Magnus Nordborg,Detlef WeigelStudies of the model plant Arabidopsis thaliana may seem to have little impact on advances in medical research, yet a survey of the scientific literature shows that this is a misconception. Many discoveries with direct relevance to human health and disease have been elaborated using Arabidopsis, an... ( view more )d several processes important to human biology are more easily studied in this versatile model plant. ( view less ) Louise A Prince,Elliot Rodriquez,James Campagna,Lawrence Brown,Daisy Fischer,William D Grant INTRODUCTION: The purpose of this study was to determine the prevalence of incidentally discovered hyperglycemia in patients with non-glucose-related complaints and to consider the potential care implications. METHODS: A retrospective chart review identified patients older than 18 years with obtain... ( view more )ed serum glucose levels. Patients with diabetic ketoacidosis were excluded. Three levels of hyperglycemia (> or = 126, > or = 140, and > or = 200 mg/dL) were considered. RESULTS: Of 2473 adult patients, 290 patients (11.7%) had serum glucose values greater than or equal to 126 mg/dL. There were 154 patients with hyperglycemia and no prior history of diabetes (6.2% of the emergency department [ED] population, 53.1% of those with hyperglycemia). CONCLUSION: More than half of the patients found to be hyperglycemic had no known history of diabetes and were being seen for a non-glucose-related complaint. The reason for this prevalence and its impact on the health of these patients is unclear. Whether ED intervention would be helpful remains unanswered. ( view less ) David C Radley,Daniel J Gottlieb,Elliot S Fisher,Anna N A Tosteson OBJECTIVE: To determine the magnitude and importance of declines in model performance associated with altering the data source and time frame from which comorbid conditions were identified in claims-based risk adjustment among persons with hip fracture. STUDY DESIGN AND SETTING: Medicare claims dat... ( view more )a were used to identify incident hip fracture cases in 1999. Three risk-adjustment instruments were evaluated: one by Iezzoni, the Charlson Index (Romano adaptation), and the Clinical Classification Software (CCS). Several implementation strategies, defined by altering data source (MedPar and/or Part B claims) and time frame (index hospitalization and/or 1-year preperiod), were assessed for each instrument. Logistic regression was used to predict 1-year mortality, and model performance was compared. RESULTS: Each instrument had modest ability to predict 1-year mortality after hip fracture. The CCS performed best overall (c=0.76), followed by the Iezzoni (c=0.73) and Charlson models (c=0.72). Although each instrument performed most favorably when applied to both inpatient and outpatient claims and when comorbidities were considered during the preperiod, varying data source and time frame had trivial effects on model performance. CONCLUSION: The similar predictive ability of the three risk-adjustment instruments suggests that ease of implementation be a key consideration in choosing an approach for hip fracture populations. ( view less ) Alan L James,Francis H Green,Michael J Abramson,Tony R Bai,Marisa Dolhnikoff,Thais Mauad,Karen O McKay,John G Elliot The perimeter of the basement membrane (Pbm) of an airway viewed in cross section is used as a marker of airway size because in normal lungs it is relatively constant, despite variations in airway smooth muscle (ASM) shortening and airway collapse. In vitro studies (McParland BE, Pare PD, Johnson P... ( view more )R, Armour CL, Black JL. J Appl Physiol 97: 556-563, 2004; Noble PB, Sharma A, McFawn PK, Mitchell HW. J Appl Physiol 99: 2061-2066, 2005) have suggested that differential stretch of the Pbm between asthmatic and nonasthmatic airways fixed in inflation may occur and lead to an overestimation of ASM thickness in asthma. The relationships between the Pbm and the area of ASM were compared in transverse sections of airways from cases of fatal asthma (F) and from nonasthmatic control (C) cases where the lung tissue had been fixed inflated (Fi; Ci) or uninflated (Fu; Cu). When all available airways were used, the regression slopes were increased in Fu and Cu, compared with Fi and Ci, and increased in Fu and Fi, compared with Cu and Ci, suggesting effects of both inflation and asthma group, respectively. When analyses were limited to airway sizes that were available for all groups (Pbm < 15 mm), the slopes of Fi and Fu were similar, but both were greater than Ci and Cu, which were also similar. It was calculated that the effect of asthma group accounted for 80% and inflation for 20% of the differences between Fi and Ci. We conclude that the effects of inflation on the relationship between Pbm and ASM are small and do not account for the differences observed in ASM between cases of asthma and nonasthmatic controls. ( view less ) Alexis E Duncan,Carolyn E Sartor,Jeffrey F Scherrer,Julia D Grant,Andrew C Heath,Elliot C Nelson,Theodore Jacob,Kathleen Keenan Bucholz AIM: This study examines the association between childhood physical abuse (CPA) and sexual abuse (CSA) and the development of cannabis abuse and dependence among adolescents and young adults while controlling for genetic and environmental risk factors. DESIGN: To control for familial risk differenc... ( view more )es related to paternal drug dependence that might confound the relationship between CSA and CPA and cannabis abuse/dependence, we created four groups based on father's and uncle's substance use dependence (SUD) status reflecting different degrees of genetic and environmental risks to offspring: (i) high genetic, high environmental risk; (ii) high genetic, low environmental risk; (iii) medium genetic, low environmental risk; and (iv) low genetic, low environmental risk. PARTICIPANTS: Adolescent and young adult offspring of monozygotic and dizygotic US military veteran twin fathers (n = 819). MEASUREMENTS: Data on CPA and CSA, DSM-IV offspring cannabis abuse/dependence, other SUD and psychopathology and maternal and paternal SUD and psychopathology were collected via semi-structured telephone interview. FINDINGS: Twenty-three per cent of the offspring sample met life-time criteria for cannabis abuse/dependence and 8.55% and 12.82% reported CSA and CPA, respectively. Offspring exposed to CSA, but not CPA, were at significantly greater risk of developing cannabis abuse/dependence compared to those who had not experienced CSA (hazard ratio = 2.16; 95% confidence interval = 1.48-3.16) after controlling for genetic and familial environmental risk and offspring gender, alcohol abuse and dependence and conduct disorder. CONCLUSIONS: These results indicate that there are effects of CSA on development of cannabis abuse/dependence in addition to the genetic and familial environmental risk imparted by having a drug-dependent father. ( view less ) Marites P Melancon,Wei Lu,Zhi Yang,Rui Zhang,Zhi Cheng,Andrew M Elliot,Jason Stafford,Tammy Olson,Jin Z Zhang,Chun Li Laser-induced phototherapy is a new therapeutic use of electromagnetic radiation for cancer treatment. The use of targeted plasmonic gold nanoparticles can reduce the laser energy necessary for selective tumor cell destruction. However, the ability for targeted delivery of the currently used gold n... ( view more )anoparticles to tumor cells is limited. Here, we describe a new class of molecular specific photothermal coupling agents based on hollow gold nanoshells (HAuNS; average diameter, approximately 30 nm) covalently attached to monoclonal antibody directed at epidermal growth factor receptor (EGFR). The resulting anti-EGFR-HAuNS exhibited excellent colloidal stability and efficient photothermal effect in the near-infrared region. EGFR-mediated selective uptake of anti-EGFR-HAuNS in EGFR-positive A431 tumor cells but not IgG-HAuNS control was shown in vitro by imaging scattered light from the nanoshells. Irradiation of A431 cells treated with anti-EGFR-HAuNS with near-infrared laser resulted in selective destruction of these cells. In contrast, cells treated with anti-EGFR-HAuNS alone, laser alone, or IgG-HAuNS plus laser did not show observable effect on cell viability. Using (111)In-labeled HAuNS, we showed that anti-EGFR-HAuNS could be delivered to EGFR-positive tumors at 6.8% ID/g, and the microscopic image of excised tumor with scattering signal from nanoshells confirmed preferential delivery to A431 tumor of anti-EGFR-HAuNS compared with IgG-HAuNS. The absence of silica core, the relatively small particle size and high tumor uptake, and the absence of cytotoxic surfactant required to stabilize other gold nanoparticles suggest that immuno-HAuNS have the potential to extend to in vivo molecular therapy. [Mol Cancer Ther 2008;7(6):1730-9]. ( view less ) J Elliot Carter,Javier A Laurini,Tara N Evans,Benjamin Estrada Candida parapsilosis is an extremely rare cause of meningitis. We report the case of a neonate born at 26+4 weeks of gestation who was admitted to the neonatal intensive care unit at our institution due to respiratory immaturity. During the course of a 3-month hospitalization, the neonate developed... ( view more ) fever and lethargy. A lumbar puncture revealed milky-white, turbid cerebrospinal fluid which contained many nucleated cells, mostly neutrophils. Microscopic examination of the cerebrospinal fluid revealed marked acute inflammation and fungal yeast forms, and cultures of the cerebrospinal fluid and peripheral blood yielded C. parapsilosis. Imaging studies subsequently revealed a subdural empyema related to epidural migration of a central venous catheter (CVL). The neonate received extended therapy with amphotericin B and fluconazole. He responded favorably to therapy and was discharged 3 months after birth. This case underscores the clinical importance of the recognition and treatment of a potentially lethal fungal pathogen of the central nervous system and the need for awareness of complications resulting from CVL malposition. ( view less ) Erin A Kolbrich,Robert S Goodwin,David A Gorelick,Robert J Hayes,Elliot A Stein,Marilyn A Huestis This study examines the plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) in young adults for up to 143 hours after drug administration. Sevente... ( view more )en female and male participants (black, white, and Hispanic) received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral MDMA doses (comparable to recreational doses) in a double-blind, randomized, balanced, within-subject design while residing on a closed research unit. Doses were separated by 1 week or more. A fully validated two-dimensional gas chromatography/mass spectrometry method simultaneously quantified MDMA, HMMA, MDA, and HMA. Calibration curves were MDA, 1 to 100 ng/mL; HMA, 2.5 to 100 ng/mL; and MDMA and HMMA, 2.5 to 400 ng/mL. Mean +/- standard deviation maximum plasma concentrations (C(max)) of 162.9 +/- 39.8 and 171.9 +/- 79.5 ng/mL were observed for MDMA and HMMA, respectively, after low-dose MDMA. After the high dose, mean MDMA Cmax significantly increased to 291.8 +/- 76.5 ng/mL, whereas mean HMMA C(max) was unchanged at 173.5 +/- 66.3 ng/mL. High intersubject variability in C(max) was observed. Mean MDA C(max) were 8.4 +/- 2.1 (low) and 13.8 +/- 3.8 (high) ng/mL. HMA Cmax were 3.5 +/- 0.4 and 3.9 +/- 0.9 ng/mL after the low and high doses, respectively. AUC infinity displayed similar trends to C(max), demonstrating nonlinear pharmacokinetics. Times of last plasma detection were generally HMA < MDA < MDMA < HMMA. Mean half-lives (t1/2) of MDMA, MDA, and HMMA were approximately 7 to 8 hours, 10.5 to 12.5 hours, and 11.5 to 13.5 hours, respectively. HMA t1/2 showed high variability. Mean MDMA volume of distribution was constant for low and high doses; clearance was significantly higher after the low dose. This study presents MDMA plasma pharmacokinetic data for the first time from blacks and females as well as measurement of HMMA and HMA concentrations after low and high MDMA doses and more frequent and extended plasma sampling than in prior studies. ( view less ) Lior Lowenstein,Mary P FitzGerald,Kimberly Kenton,Linda Brubaker,Ilan Gruenwald,Irena Papier,Ramón A Durazo-Arvizu,Christina Elliot,Elizabeth R Mueller,Yoram Vardi OBJECTIVE: The purpose of this study was to test the feasibility and validity of a continuous measurement of urinary sensation during cystometry. STUDY DESIGN: Subjects continuously recorded their level of urinary sensation during cystometry with the use of urodynamic diagnoses and responses to the... ( view more ) Medical Epidemiologic and Social Aspects of Aging (MESA) and Urinary Distress Inventory (UDI) scales. Trends in urinary sensation recordings by increasing percentage of maximum cystometric capacity (MCC) were captured and compared with the use of growth curves. RESULTS: Fifty-one women participated: 18 patients had detrusor overactivity incontinence (DOI); 15 patients had urodynamic stress incontinence; 9 patients had mixed incontinence, and 9 patients did not demonstrate incontinence. In the volume range between 35% and 75% of MCC, the mean sensation level was higher in the DOI group than the other groups (P < .04). Urge sensation at 50% of MCC correlated with UDI and MESA urge subscales (rho = 0.34, p < .03 and rho = 0.39, p < .02). CONCLUSION: This study demonstrates that the Urgeometer measurement is feasible and correlates with urodynamic diagnosis and the severity and bother from urge incontinence. ( view less ) Stephen G Ellis,Michal Tendera,Mark A de Belder,Ad J van Boven,Petr Widimsky,Luc Janssens,H R Andersen,Amadeo Betriu,Stefano Savonitto,Jerzy Adamus,Jan Z Peruga,Maciej Kosmider,Olivier Katz,Thomas Neunteufl,Julia Jorgova,Maria Dorobantu,Liliana Grinfeld,Paul Armstrong,Bruce R Brodie,Howard C Herrmann,Gilles Montalescot,Franz-Josef Neumann,Mark B Effron,Elliot S Barnathan,Eric J Topol,FINESSE Investigators  BACKGROUND: We hypothesized that percutaneous coronary intervention (PCI) preceded by early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or with abciximab alone (abciximab-facilitated PCI) would improve outcomes in patients with acute ST-segment elevation myocardi... ( view more )al infarction, as compared with abciximab administered immediately before the procedure (primary PCI). METHODS: In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximab-facilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization. RESULTS: A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P=0.01 and P=0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P=0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P=0.49). CONCLUSIONS: Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228 [ClinicalTrials.gov].) ( view less ) Elizabeth S Haswell,Rémi Peyronnet,Hélène Barbier-Brygoo,Elliot M Meyerowitz,Jean-Marie Frachisse In bacterial and animal systems, mechanosensitive (MS) ion channels are thought to mediate the perception of pressure, touch, and sound [1-3]. Although plants respond to a wide variety of mechanical stimuli, and although many mechanosensitive channel activities have been characterized in plant memb... ( view more )ranes by the patch-clamp method, the molecular nature of mechanoperception in plant systems has remained elusive [4]. Likely candidates are relatives of MscS (Mechanosensitive channel of small conductance), a well-characterized MS channel that serves to protect E. coli from osmotic shock [5]. Ten MscS-Like (MSL) proteins are found in the genome of the model flowering plant Arabidopsis thaliana[4, 6, 7]. MSL2 and MSL3, along with MSC1, a MscS family member from green algae, are implicated in the control of organelle morphology [8, 9]. Here, we characterize MSL9 and MSL10, two MSL proteins found in the plasma membrane of root cells. We use a combined genetic and electrophysiological approach to show that MSL9 and MSL10, along with three other members of the MSL family, are required for MS channel activities detected in protoplasts derived from root cells. This is the first molecular identification and characterization of MS channels in plant membranes. ( view less ) John C Cushman,Sakae Agarie,Rebecca L Albion,Stewart M Elliot,Tahar Taybi,Anne M Borland Crassulacean acid metabolism (CAM) is a specialized mode of photosynthesis that improves water use efficiency by shifting part or all of net atmospheric CO(2) uptake to the night. Genetic dissection of regulatory and metabolic attributes of CAM has been limited by the difficulty of identifying a re... ( view more )liable phenotype for mutant screening. We developed a novel and simple colorimetric assay to measure leaf pH to screen fast neutron-mutagenized populations of common ice plant (Mesembryanthemum crystallinum), a facultative CAM species, to detect CAM-deficient mutants with limited nocturnal acidification. The isolated CAM-deficient mutants showed negligible net dark CO(2) uptake compared with wild-type plants following the imposition of salinity stress. The mutants and wild-type plants accumulated nearly comparable levels of sodium in leaves, but the mutants grew more slowly than the wild-type plants. The mutants also had substantially reduced seed set and seed weight relative to wild type under salinity stress. Carbon-isotope ratios of seed collected from 4-month-old plants indicated that C(3) photosynthesis made a greater contribution to seed production in mutants compared to wild type. The CAM-deficient mutants were deficient in leaf starch and lacked plastidic phosphoglucomutase, an enzyme critical for gluconeogenesis and starch formation, resulting in substrate limitation of nocturnal C(4) acid formation. The restoration of nocturnal acidification by feeding detached leaves of salt-stressed mutants with glucose or sucrose supported this defect and served to illustrate the flexibility of CAM. The CAM-deficient mutants described here constitute important models for exploring regulatory features and metabolic consequences of CAM. ( view less ) Mikel Sadek,Robert L Hynecek,Elliot B Sambol,Habib Ur-Rehman,K Craig Kent,Peter L Faries OBJECTIVE: Carotid angioplasty and stenting (CAS) is a percutaneous alternative to carotid endarterectomy (CEA) for treating patients with carotid artery stenosis. This study sought to evaluate whether patients at increased perioperative risk for CEA may be treated with CAS while maintaining equiva... ( view more )lent outcomes. METHODS: This study was a nonblinded, retrospective analysis of data obtained from September 2002 to present in the CAS group and from January 1997 to present in the CEA group. Two hundred thirty-one CAS and 647 CEA procedures were performed. Patients were selected for CAS based on criteria that placed them at increased risk for standard CEA surgery. Except for percentage women treated, baseline demographics did not differ between patients treated with CAS and CEA: mean age (72.0 years [range 46-94] vs 70.5 years [range 42-92], P = NS), mean follow-up (12.8 +/- 11.8 months vs 8.7 +/- 10.0 months, P = NS) and percentage women treated (41.4% vs 32.3%, P = .03). Cerebral protection devices were used in 228/231 patients treated with CAS, and each patient underwent an NIH Stroke Scale assessment 24 hours postoperatively and at 30 days follow-up by an independent observer. RESULTS: Preoperative neurologic symptoms did not differ between patients treated with CAS and CEA: amaurosis fugax (6.06% vs 6.96%, P = NS), transient ischemic attacks (13.4% vs 13.9%, P = NS), strokes (19.9% vs 14.1%, P = NS) and total symptoms (27.7% vs 30.5%, P = NS). Due to the selection of patient groups based on predefined clinical characteristics, factors associated with an increased risk of complications from standard CEA surgery were generally more prevalent in patients treated with CAS: neck irradiation (6.06% vs 1.24%, P < .001), neck dissection for cancer therapy (7.8% vs 1.5%, P < .001), prior ipsilateral CEA (15.2% vs 3.4%, P = .001), contralateral carotid artery occlusion (12.1% vs 1.1%, P < .001), modified Goldman Cardiac Risk II-moderate risk (26.0% vs 11.3%, P < .001) and modified Goldman Cardiac Risk III-high risk (16.4% vs 2.1%, P < .001) in patients treated with CAS and CEA, respectively. Perioperative outcomes did not differ between patients treated with CAS and CEA: myocardial infarction (MI) (1.7% vs 2.6%, P = NS), stroke without residual symptoms (1.3% vs 1.2%, P = NS), stroke with residual symptoms (0.4% vs 0.8%, P = NS), mortality (0.4% vs 0.6%, P = NS), and total MI/stroke/mortality rate (3.9% vs 5.3%, P = NS). CONCLUSIONS: The data in this study demonstrate that high-risk patients undergoing CAS had comparable outcomes to low-risk patients undergoing CEA. This study supports the use of CAS as a reasonable alternative for patients at increased perioperative risk for CEA. ( view less ) Rozenn N Lemaitre,David S Siscovick,Elliot M Berry,Jeremy D Kark,Yechiel Friedlander The fatty acid composition of membranes plays an important role in health and diseases. Whether genetic factors play a role in interindividual variability in membrane fatty acid levels has received limited attention. Using variance decomposition methods, we estimated the heritability of red blood c... ( view more )ell (RBC) membrane fatty acids in an unselected population sample of 80 families (205 male and 212 female subjects) living in kibbutz settlements in Israel. Fatty acid levels were measured by gas chromatography. We estimated that polygenes explained 40% to 70% of the sex- and age-adjusted interindividual variability in all RBC fatty acids: saturated, monounsaturated, and polyunsaturated. The heritability estimates remained very similar after further adjustment for smoking, alcohol consumption, physical activity, lipoproteins, body mass index, waist to hip ratio, education, and religiosity. In bivariate genetic analyses, we observed positive genetic correlations for the fatty acid pairs 20:4n6-22:6n3 and 20:5n3-22:6n3, and negative genetic correlations for the pairs 16:0-20:4n6, 16:0-22:6n3, 18:1n9-20:3n6, 18:2n6-20:4n6, 18:2n6-24:0, and 20:3n6-20:4n6, suggesting that shared effects of the same sets of loci account for 12% to 30% of the additive genetic variance in these pairs of fatty acids. This study suggests a considerable polygenic component for all RBC membrane fatty acids and provides evidence that shared genetic effects account for the additive genetic variance in various fatty acid pairs. Future studies are needed to map the genes underlying the interindividual variation in these inherited phenotypes. ( view less ) Carolyn J Heckman,Elliot J Coups,Sharon L Manne BACKGROUND: Little is known about the prevalence of indoor tanning among the US general adult population. OBJECTIVES: This study sought to: (1) describe the prevalence of indoor tanning throughout adulthood; (2) identify demographic and psychosocial correlates of indoor tanning; and (3) determine w... ( view more )hether these correlates vary by age group. METHODS: This study used data from the 2005 National Health Interview Survey, an annual health survey of the US adult population. RESULTS: Indoor tanning rates were higher among individuals who were young, white, and female. Rates of indoor tanning in the last year varied from 20.4% for those aged 18 to 29 years to 7.8% for those aged 65 years and older. A variety of demographic, health, and behavioral health risk factors correlated with indoor tanning. LIMITATIONS: The study design was cross-sectional and all data were self-reported. CONCLUSIONS: Health care providers should address indoor tanning as a health risk factor across the lifespan. ( view less ) Michal Granot,Irit Weissman-Fogel,Yonathan Crispel,Dorit Pud,Yelena Granovsky,Elliot Sprecher,David Yarnitsky Descending modulation of pain can be demonstrated psychophysically by dual pain stimulation. This study evaluates in 31 healthy subjects the association between parameters of the conditioning stimulus, gender and personality, and the endogenous analgesia (EA) extent assessed by diffuse noxious inhi... ( view more )bitory control (DNIC) paradigm. Contact heat pain was applied as the test stimulus to the non-dominant forearm, with stimulation temperature at a psychophysical intensity score of 60 on a 0-100 numerical pain scale. The conditioning stimulus was a 60s immersion of the dominant hand in cold (12, 15, 18 degrees C), hot (44 and 46.5 degrees C), or skin temperature (33 degrees C) water. The test stimulus was repeated on the non-dominant hand during the last 30s of the conditioning immersion. EA extent was calculated as the difference between pain scores of the two test stimuli. State and trait anxiety and pain catastrophizing scores were assessed prior to stimulation. EA was induced only for the pain-generating conditioning stimuli at 46.5 degrees C (p=0.011) and 12 degrees C (p=0.003). EA was independent of conditioning pain modality, or personality, but a significant gender effect was found, with greater EA response in males. Importantly, pain scores of the conditioning stimuli were not correlated with EA extent. The latter is based on both our study population, and on additional 82 patients, who participated in another study, in which EA was induced by immersion at 46.5 degrees C. DNIC testing, thus, seems to be relatively independent of the stimulation conditions, making it an easy to apply tool, suitable for wide range applications in pain psychophysics. ( view less ) Elliot V Hersh,Ramesh Balasubramaniam,Andres PintoAlthough there are theoretically numerous pharmacologic targets for relieving temporomandibular disorder (TMD)-associated pains, evidence-based literature clearly establishing the efficacy and safety of drugs in the TMD population is limited at best. This article reviews the pharmacology, toxicolog... ( view more )y, and research supporting the use of a host of pharmacologic agents that have been used in patients who have TMD, including nonsteroidal anti-inflammatory drugs, corticosteroids, benzodiazepines, nonbenzodiazepine sedative hypnotics, opioids, skeletal muscle relaxants, capsaicin, transdermal lidocaine, antidepressants, and anticonvulsants. Recommendations regarding the proper use of each drug class are also made. ( view less )
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