Anatomy Commons^™

Sputum Neutrophils As A Biomarker In Copd: Findings From The Eclipse Study, Dave Singh, Lisa Edwards, Ruth Tal-Singer, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.

METHODS: Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.

RESULTS: Sputum neutrophil % …

Characterisation Of Copd Heterogeneity In The Eclipse Cohort, Alvar Agusti, Peter M.A. Calverley, Bartolome Celli, Harvey O. Coxson, Lisa D. Edwards, David A. Lomas, William Macnee, Bruce E. Miller, Steve I. Rennard, Edwin K. Silverman, Ruth Tal-Singer, Emiel Wouters, Julie C. Yates, Jørgen Vestbo, The Evaluation Of Copd Longitudinally To Identify Predictive Surrogate Endpoints (Eclipse) Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).

METHODS: We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.

RESULTS: COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in …

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …

Parent- Versus Child-Reported Functional Health Status After The Fontan Procedure., Linda M. Lambert, L Luann Minich, Jane W. Newburger, Minmin Lu, Victoria L. Pemberton, Ellen A. Mcgrath, Andrew M. Atz, Mingfen Xu, Elizabeth Radojewski, Darlene Servedio, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: We sought to compare perceptions of functional health status between children who had undergone a Fontan procedure and their parents.

METHODS: Fontan procedure survivors 10 to 18 years of age were included in the study if the child completed the Child Health Questionnaire (CHQ) and the parent completed the parent form to assess the child's functional health status. Comparisons were made between raw domain scores for the parent- and child-completed CHQs.

RESULTS: Between March 2003 and April 2004, 1078 Fontan survivors were screened. Of the 546 eligible and consented patients, 354 were 10-18 years of age and 328 parent/child …

Functional State Following The Fontan Procedure., Ismee A. Williams, Lynn A. Sleeper, Steven D. Colan, Minmin Lu, Elizabeth A. Stephenson, Jane W. Newburger, Welton M. Gersony, Meryl S. Cohen, James F. Cnota, Andrew M. Atz, Richard V. Williams, Renee Margossian, Andrew J. Powell, Mario P. Stylianou, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function.

METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by …

Comparison Of Echocardiographic And Cardiac Magnetic Resonance Imaging Measurements Of Functional Single Ventricular Volumes, Mass, And Ejection Fraction (From The Pediatric Heart Network Fontan Cross-Sectional Study)., Renee Margossian, Marcy L. Schwartz, Ashwin Prakash, Lisa Wruck, Steven D. Colan, Andrew M. Atz, Timothy J. Bradley, Mark A. Fogel, Lynne M. Hurwitz, Edward Marcus, Andrew J. Powell, Beth F. Printz, Michael D. Puchalski, Jack Rychik, Girish S. Shirali, Richard Williams, Shi-Joon Yoo, Tal Geva, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement …

Striatal Neuroinflammation Promotes Parkinsonism In Rats, Dong-Young Choi, Mei Liu, Randy L. Hunter, Wayne A. Cass, Jignesh D. Pandya, Patrick G. Sullivan, Eun-Joo Shin, Hyoung-Chun Kim, Don M. Gash, Guoying Bing

Neuroscience Faculty Publications

BACKGROUND: Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD.

FINDINGS: In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS)-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS) …

Smoking Enhances Risk For New External Genital Warts In Men, Dorothy J. Wiley, David Elashoff, Emmanuel V. Masongsong, Diane M. Harper

Dartmouth Scholarship

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.

Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang

Dartmouth Scholarship

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.

Rationale And Design Of A Trial Of Angiotensin-Converting Enzyme Inhibition In Infants With Single Ventricle., Daphne T. Hsu, Seema Mital, Chitra Ravishankar, Renee Margossian, Jennifer S. Li, Lynn A. Sleeper, Richard V. Williams, Jami C. Levine, Brian W. Mccrindle, Andrew M. Atz, Darlene Servedio, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.

METHODS: The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates < or =45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.

RESULTS: A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to …

Design And Rationale Of A Randomized Trial Comparing The Blalock-Taussig And Right Ventricle-Pulmonary Artery Shunts In The Norwood Procedure., Richard G. Ohye, J William Gaynor, Nancy S. Ghanayem, Caren S. Goldberg, Peter C. Laussen, Peter C. Frommelt, Jane W. Newburger, Gail D. Pearson, Sarah Tabbutt, Gil Wernovsky, Lisa M. Wruck, Andrew M. Atz, Steve D. Colan, James Jaggers, Brian W. Mccrindle, Ashwin Prakash, Michael D. Puchalski, Lynn A. Sleeper, Mario P. Stylianou, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The initial palliative procedure for patients born with hypoplastic left heart syndrome and related single right ventricle anomalies, the Norwood procedure, remains among the highest risk procedures in congenital heart surgery. The classic Norwood procedure provides pulmonary blood flow with a modified Blalock-Taussig shunt. Improved outcomes have been reported in a few small, nonrandomized studies of a modification of the Norwood procedure that uses a right ventricle-pulmonary artery shunt to provide pulmonary blood flow. Other nonrandomized studies have shown no differences between the two techniques.

METHODS: The Pediatric Heart Network designed a randomized clinical trial to compare outcomes for …

Functional Status, Heart Rate, And Rhythm Abnormalities In 521 Fontan Patients 6 To 18 Years Of Age., Andrew D. Blaufox, Lynn A. Sleeper, David J. Bradley, Roger E. Breitbart, Allan Hordof, Ronald J. Kanter, Elizabeth A. Stephenson, Mario Stylianou, Victoria L. Vetter, J Philip Saul, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Our objective was to determine the relationship between functional outcome and abnormalities of heart rate and rhythm after the Fontan operation.

METHODS: The National Heart, Lung, and Blood Institute Pediatric Heart Network conducted a cross-sectional analysis of patients who had undergone a Fontan procedure at the 7 network centers. Analysis was based on 521 patients with an electrocardiogram (n = 509) and/or bicycle exercise test (n = 404). The Child Health Questionnaire parent report and the oxygen consumption at the anaerobic threshold were used as markers of functional outcome.

RESULTS: Various Fontan procedures had been performed: intracardiac lateral tunnel …

Current Significance Of Meconium Plug Syndrome., Scott J. Keckler, Shawn D. St Peter, Troy L. Spilde, Kuojen Tsao, Daniel J. Ostlie, G W. Holcomb Iii, Charles L. Snyder

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The significance of meconium plug syndrome is dependent on the underlying diagnosis. The incidence of pathologic finding, particularly Hirschsprung's disease, contributing to the presence of these plugs, has been debated. However, there are little recent data in the literature. Therefore, we reviewed our experience with meconium plugs as a cause of abdominal distension to evaluate the associated conditions and incidence of Hirschsprung's disease.

METHODS: We reviewed the records of newborns with meconium plugs found in the distal colon on contrast enema from 1994 to 2007. Demographics, radiologic findings, histologic findings, operative findings, and clinical courses were reviewed.

RESULTS: During …

Bradykinin Type 2 Receptor Be1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition, Gary Van Guilder, Mias Pretorius, James M Luther, J Brian Byrd, Kevin Hill, James V Gainer, Nancy J Brown

Health and Nutritional Sciences Faculty Publications

To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1+9/-9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/-9:-9/-9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4+/-2.8, 113.8+/-1.8, and 110.6+/-1.8 mm Hg in +9/+9, +9/-9, and -9/-9 groups, respectively; P=0.007). In the absence of enalaprilat, bradykinin-stimulated forearm blood flow, forearm vascular resistance, and net t-PA release were similar among genotype groups. Enalaprilat increased …

One-Year Treatment With Mometasone Furoate In Chronic Obstructive Pulmonary Disease, Peter M.A. Calverley, Stephen I. Rennard, Harold S. Nelson, Jill P. Karpel, Eduardo H. Abbate, Paul Stryszak, Heribert Staudinger

Journal Articles: Pulmonary & Critical Care Med

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse …

Survival After Bidirectional Cavopulmonary Anastomosis: Analysis Of Preoperative Risk Factors., Mark A. Scheurer, Elizabeth G Hill, Nagavardhan Vasuki, Scott Maurer, Eric M. Graham, Varsha Bandisode, Girish S. Shirali, Andrew M. Atz, Scott M. Bradley

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prognostic factors for survival after bidirectional cavopulmonary anastomosis for functionally single ventricle are not well defined. We analyzed preoperative hemodynamic and echocardiographic data to determine risk factors for death or transplantation at least 1 year after bidirectional cavopulmonary anastomosis.

METHODS: Data for all patients who underwent bidirectional cavopulmonary anastomosis before 5 years of age at our institution from September 1995 through June 2005 were analyzed. Available preoperative echocardiograms and catheterizations were reviewed. Survivors were compared with those who died or underwent transplantation. Bivariable associations between demographic and clinical risk factors and survival status (alive without transplantation vs dead or …

Prenatal Cocaine Exposure Alters Alpha2 Receptor Expression In Adolescent Rats, Rosemarie M. Booze, David R. Wallace, Janelle M. Silvers, Barbara J. Strupp, Diane M. Snow, Charles F. Mactutus

Neuroscience Faculty Publications

BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured alpha2-adrenergic receptor (alpha2-AR) density in adolescent (35-days-old) rats, using [3H]RX821002 (5 nM).

RESULTS: Sex-specific alterations of alpha2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of alpha2-AR in parietal cortex.

CONCLUSION: These data suggest that prenatal cocaine exposure results in a persistent alteration …

Hepatic Disposition Of Cyclosporine A In Isolated Perfused Rat Livers, Reza Mehvar, Anjaneya Chimalakonda

Pharmacy Faculty Articles and Research

PURPOSE. To develop an isolated perfused rat liver model to study the hepatic disposition of cyclosporine A (CyA) in both sexes.

METHODS. Livers were isolated from male (n = 6) and female (n = 7) rats and perfused with a physiological buffer in a single-pass manner. A bolus 1-mg dose of CyA was injected into the inlet catheter and periodical samples (0-15 min) were collected from the outlet perfusate. The concentrations of CyA in the outlet perfusate, collected bile (0-15 min), and liver tissue (at the end of perfusion) were quantitated by HPLC and subjected to statistical moment analysis. …

Posttransplant Recoarctation Of The Aorta: A Twelve Year Experience., Girish S. Shirali, C E. Cephus, M A. Kuhn, K K. Ogata, L K. Vander Dussen, R E. Chinnock, N F. Mulla, J K. Johnston, L L. Bailey, S R. Gundry, A J. Razzouk, R L. Larsen

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: This study was undertaken to investigate the incidence of posttransplant recoarctation of the aorta, delineate the mode of presentation, identify risk factors that predict recoarctation and examine the results of intervention for posttransplant recoarctation.

BACKGROUND: Patients with aortic arch hypoplasia require extended arch reconstruction at transplant, with an inherent possibility of subsequent recoarctation of the aorta.

METHODS: This was a retrospective review of all children (ageyears) who underwent cardiac transplantation over a 10-year period. Collected data included pretransplant diagnosis, details of the transplant procedure and posttransplant data including development of recoarctation of the aorta, interventions for recoarctation and the …

Ventricular Remodeling Following Infant-Pediatric Cardiac Transplantation. Does Age At Transplantation Or Size Disparity Matter?, Girish S. Shirali, F Lombano, W L. Beeson, D A. Dyar, N F. Mulla, A Khan, J K. Johnston, R E. Chinnock, S R. Gundry, A J. Razzouk

Manuscripts, Articles, Book Chapters and Other Papers

Early left ventricular (LV) remodeling following pediatric cardiac transplantation has not been described. To identify patterns and determinants of change in left ventricular mass and volume posttransplant, we studied 125 consecutive children who underwent cardiac transplantation between January 1, 1989 and July 31, 1993. Two-dimensional imaging-directed M-mode echocardiograms were studied weekly until 26 weeks post-transplant. LV mass and volume (indexed to BSA1.5) were measured. LV mass index increased until 3 weeks post-transplant, and then decreased. The mean decrement in LV mass index after 8 weeks post-transplant (relative to baseline) was significantly larger in patients with donor-recipient weight ratio > 1.5 compared …