Medicine and Health Sciences Commons^™

Hla-Dpb1 And Dpb2 Are Genetic Loci For Systemic Sclerosis: A Genome-Wide Association Study In Koreans With Replication In North Americans, Xiaodong Zhou, Jong Eun Lee, Frank C Arnett, Momiao Xiong, Min Young Park, Yeon Kyeong Yoo, Eun Soon Shin, John D Reveille, Maureen D Mayes, Jin Hyun Kim, Ran Song, Ji Yong Choi, Ji Ah Park, Yun Jong Lee, Eun Young Lee, Yeong Wook Song, Eun Bong Lee

Journal Articles

OBJECTIVE: To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.

METHODS: A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.

RESULTS: The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were …

Comparing Clinician Knowledge And Online Information Regarding Alli (Orlistat), Stuart Nelson, Kevin O Hwang, Elmer V Bernstam

Journal Articles

BACKGROUND: Many consumers join online communities focused on health. Online forums are a popular medium for the exchange of health information between consumers, so it is important to determine the accuracy and completeness of information posted to online forums.

OBJECTIVE: We compared the accuracy and completeness of information regarding the FDA-approved over-the counter weight-loss drug Alli (Orlistat) from forums and from clinicians.

METHODS: We identified Alli-related questions posted on online forums and then posed the questions to 11 primary care providers. We then compared the clinicians' answers to the answers given on the forums. A panel of blinded experts evaluated …

Adherence To Host Extracellular Matrix And Serum Components By Enterococcus Faecium Isolates Of Diverse Origin, Meng Zhao, Jouko Sillanpää, Sreedhar R Nallapareddy, Barbara E Murray

Journal Articles

Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to …

Keap1 E3 Ligase-Mediated Downregulation Of Nf-Kappab Signaling By Targeting Ikkbeta., Dung-Fang Lee, Hsu-Ping Kuo, Mo Liu, Chao-Kai Chou, Weiya Xia, Yi Du, Jia Shen, Chun-Te Chen, Longfei Huo, Ming-Chuan Hsu, Chia-Wei Li, Qingqing Ding, Tsai-Lien Liao, Chien-Chen Lai, Ann-Chi Lin, Ya-Hui Chang, Shih-Feng Tsai, Long-Yuan Li, Mien-Chie Hung

Journal Articles

IkappaB kinase beta (IKKbeta) is involved in tumor development and progression through activation of the nuclear factor (NF)-kappaB pathway. However, the molecular mechanism that regulates IKKbeta degradation remains largely unknown. Here, we show that a Cullin 3 (CUL3)-based ubiquitin ligase, Kelch-like ECH-associated protein 1 (KEAP1), is responsible for IKKbeta ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKKbeta and to upregulation of NF-kappaB-derived tumor angiogenic factors. A systematic analysis of the CUL3, KEAP1, and RBX1 genomic loci revealed a high percentage of genome loss and missense mutations in human cancers that failed to facilitate IKKbeta degradation. Our …

Ethnic Differences In Do-Not-Resuscitate Orders After Intracerebral Hemorrhage, Darin B Zahuranec, Devin L Brown, Lynda D Lisabeth, Nicole R Gonzales, Paxton J Longwell, Melinda A Smith, Nelda M Garcia, Lewis B Morgenstern

Journal Articles

OBJECTIVE: To explore ethnic differences in do-not-resuscitate orders after intracerebral hemorrhage.

DESIGN: Population-based surveillance.

SETTING: Corpus Christi, Texas.

PATIENTS: All cases of intracerebral hemorrhage in the community of Corpus Christi, TX were ascertained as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for do-not-resuscitate orders. Unadjusted and multivariable logistic regression were used to test for associations between ethnicity and do-not-resuscitate orders, both overall ("any do-not-resuscitate") and within 24 hrs of presentation ("early do-not-resuscitate"), adjusted for age, gender, Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage, infratentorial hemorrhage, …

Advances In Progenitor Cell Therapy Using Scaffolding Constructs For Central Nervous System Injury, Peter A Walker, Kevin R Aroom, Fernando Jimenez, Shinil K Shah, Matthew T Harting, Brijesh S Gill, Charles S Cox

Journal Articles

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and …

Clinical Decision Support Capabilities Of Commercially-Available Clinical Information Systems., Adam Wright, Dean F Sittig, Joan S Ash, Sapna Sharma, Justine E Pang, Blackford Middleton

Journal Articles

BACKGROUND: The most effective decision support systems are integrated with clinical information systems, such as inpatient and outpatient electronic health records (EHRs) and computerized provider order entry (CPOE) systems. Purpose The goal of this project was to describe and quantify the results of a study of decision support capabilities in Certification Commission for Health Information Technology (CCHIT) certified electronic health record systems.

METHODS: The authors conducted a series of interviews with representatives of nine commercially available clinical information systems, evaluating their capabilities against 42 different clinical decision support features.

RESULTS: Six of the nine reviewed systems offered all the applicable …

Modern Approaches To Pediatric Brain Injury Therapy, Peter A Walker, Matthew T Harting, James E Baumgartner, Stephen Fletcher, Nathan Strobel, Charles S Cox

Journal Articles

Each year, pediatric traumatic brain injury (TBI) accounts for 435,000 emergency department visits, 37,000 hospital admissions, and approximately 2,500 deaths in the United States. TBI results in immediate injury from direct mechanical force and shear. Secondary injury results from the release of biochemical or inflammatory factors that alter the loco-regional milieu in the acute, subacute, and delayed intervals after a mechanical insult. Preliminary preclinical and clinical research is underway to evaluate the benefit from progenitor cell therapeutics, hypertonic saline infusion, and controlled hypothermia. However, all phase III clinical trials investigating pharmacologic monotherapy for TBI have shown no benefit. A recent …

Improving Clinical Quality Indicators Through Electronic Health Records: It Takes More Than Just A Reminder., Dean F Sittig, Jonathan M Teich, Jerome A Osheroff, Hardeep Singh

Journal Articles

No abstract provided.

Therapeutic Targeting Of Atp7b In Ovarian Carcinoma., Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood

Journal Articles

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.

EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

RESULTS: ATP7A …

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma., Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Journal Articles

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Comorbidities, Patient Knowledge, And Disease Management In A National Sample Of Patients With Copd, R Graham Barr, Bartolome R Celli, David M Mannino, Thomas Petty, Stephen I Rennard, Frank C Sciurba, James K Stoller, Byron M Thomashow, Gerard M Turino

Journal Articles

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often undertreated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD.

METHODS: A survey was administered by telephone in 2006 to 1003 patients with COPD to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%.

RESULTS: …

Antibiotic Resistance In Staphylococcus Aureus-Containing Cutaneous Abscesses Of Patients With Hiv, Gus W Krucke, Deanna E Grimes, Richard M Grimes, Thai D Dang

Journal Articles

PURPOSE: The aim of this study was to document the resistance patterns found in exudates from cutaneous abscesses of HIV-infected persons.

BASIC PROCEDURES: Patient records were reviewed on 93 culture and sensitivity tests performed on exudates taken from incised and drained abscesses of HIV-infected persons.

MAIN FINDINGS: Of the specimens, 84.6% were Staphylococcus aureus. Of these, 93.5% were penicillin resistant, 87% oxacillin resistant, 84.4% cephazolin resistant, 84.4% erythromycin resistant, 52.2% ciprofloxacin resistant, and 15.6% tetracycline resistant. Fifty-eight specimens were tested for clindamycin with 29.3% found resistant; 85.7% were methicillin-resistant S aureus (MRSA) (defined as resistant to both penicillin G and …

Creb Mediates Prostaglandin F2alpha-Induced Muc5ac Overexpression., Wen-Cheng Chung, Seung-Hee Ryu, Hongxia Sun, Darryl C Zeldin, Ja Seok Koo

Journal Articles

Mucus secretion is an important protective mechanism for the luminal lining of open tubular organs, but mucin overproduction in the respiratory tract can exacerbate the inflammatory process and cause airway obstruction. Production of MUC5AC, a predominant gel-forming mucin secreted by airway epithelia, can be induced by various inflammatory mediators such as prostaglandins. The two major prostaglandins involved in inflammation are PGE(2) and PGF(2alpha). PGE(2)-induced mucin production has been well studied, but the effect of PGF(2alpha) on mucin production remains poorly understood. To elucidate the effect and underlying mechanism of PGF(2alpha) on MUC5AC production, we investigated the signal transduction of PGF(2alpha) …

Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti

Journal Articles

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples …

Is Paromomycin An Effective And Safe Treatment Against Cutaneous Leishmaniasis? A Meta-Analysis Of 14 Randomized Controlled Trials, Dae Hyun Kim, Hye Jin Chung, Joachim Bleys, Reza F Ghohestani

Journal Articles

BACKGROUND: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting.

METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled …

Comparative Efficacy Of 2 Topical Anesthetics For The Placement Of Orthodontic Temporary Anchorage Devices, Derek S Reznik, Arthur H Jeske, Jung-Wei Chen, Jeryl English

Journal Articles

This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P …

Incidental Detection Of An Occult Oral Malignancy With Autofluorescence Imaging: A Case Report, Nadarajah Vigneswaran, Sheila Koh, Ann Gillenwater

Journal Articles

BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma.

CASE DESCRIPTION: A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during …

Molluscan Memory Of Injury: Evolutionary Insights Into Chronic Pain And Neurological Disorders, Edgar T Walters, Leonid L Moroz

Journal Articles

Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan …

Taxonomy Development And Knowledge Representation Of Nurses' Personal Cognitive Artifacts., Sharon Mclane, James P Turley

Journal Articles

Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive …

Improving Follow-Up Of Abnormal Cancer Screens Using Electronic Health Records: Trust But Verify Test Result Communication., Hardeep Singh, Lindsey Wilson, Laura A Petersen, Mona K Sawhney, Brian Reis, Donna Espadas, Dean F Sittig

Journal Articles

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response.

METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. …

Reduced Neutrophil Count In People Of African Descent Is Due To A Regulatory Variant In The Duffy Antigen Receptor For Chemokines Gene, David Reich, Michael A. Nalls, W H Linda Kao, Ermeg L. Akylbekova, Arti Tandon, Nick Patterson, James Mullikin, Wen-Chi Hsueh, Ching-Yu Cheng, Josef Coresh, Eric Boerwinkle, Man Li, Alicja Waliszewska, Julie Neubauer, Rongling Li, Tennille S. Leak, Lynette Ekunwe, Joe C. Files, Cheryl L. Hardy, Joseph M. Zmuda, Herman A. Taylor, Elad Ziv, Tamara B. Harris, James G. Wilson

Journal Articles

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. to identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. …