Medicine and Health Sciences Commons^™

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Differences In Responses Of Platelets To Fluid Shear Stress In Patients With Peripheral Artery Disease (Pad) And Coronary Artery Disease (Cad)., Vijay Nambi, Kay T Kimball, Paul Bray, Angela L Bergeron, Shawna L Johnson, Joel D Morrisett, Changyi Chen, Peter H Lin, Alan B Lumsden, Christie M Ballantyne, Jing-Fei Dong

Cardeza Foundation for Hematologic Research

Information on differences in platelet function between patients with peripheral arterial disease (PAD) and patients with coronary artery disease (CAD) is limited. We sought to examine the differences in the platelets response to shear stress in patients with PAD compared to those with CAD. Men with symptomatic PAD (ankle brachial index [ABI] < 0.9; n = 29) were compared with similarly aged men with CAD (post coronary artery bypass grafting; n = 40) but without PAD. All participants were on aspirin, and none were on clopidogrel. We measured changes in shear-induced platelet aggregation (SIPA) and shear-induced P-selectin expression (SIPE) under fluid shear rates of 5000 and 10,000 s(-1)which are typically found in arterioles and stenosed arteries, respectively. Aggregation was also induced by a combined stimulation of collagen, fluid shear stress, and adenosine diphosphate (ADP) or epinephrine using a platelet function analyzer (PFA-100) as well as optical aggregometry (arachidonic acid, collagen and epinephrine). Analyses of covariance adjusted for age, aspirin dose, and statin use were used to estimate differences between the groups. Values of SIPA at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in the PAD group, while there were no differences between the PAD and CAD groups in SIPE at both fluid shear rates. However, baseline shear-induced P-selectin expression was higher in patients with PAD than CAD (mean fluorescence intensity [MFI] = 2.93 +/- 1.37 vs.1.94 +/- 0.67; p = 0.01), while the percentage increases in SIPA and SIPE at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in patients with CAD when compared to PAD (p < 0.001 for all comparisons). Although there were several similarities in platelet function between men with PAD and men with CAD, significant differences in platelet responses to shear stress were observed in men with PAD when compared to those with CAD. Although the mechanism for these observed differences are not clear, we hypothesize that in vivo platelet activation in PAD patients may contribute to the differences and will need to be further investigated.

Laparoscopic Treatment Of Pancreatic Pseudocysts In Children., Suzanne M. Yoder, Steven Rothenberg, Kuojen Tsao, Mark L. Wulkan, Todd A. Ponsky, Shawn D. St Peter, Daniel J. Ostlie, Timothy D. Kane

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pancreatic pseudocysts are problematic sequelae of pancreatitis or pancreatic trauma causing persistent abdominal pain, nausea, and gastric outlet obstruction. Due to the low volume of disease in children, there is scant information in the literature on the operative management of pseudocysts with minimally invasive techniques. We conducted a multi-institutional review to illustrate several technical variations utilized in achieving laparoscopic cystgastrostomy in the pediatric population.

METHODS: A retrospective review was conducted of all patients who underwent laparoscopic cystgastrostomy in five institutions. Patient data, operative techniques, and postoperative course were analyzed.

RESULTS: There were 13 patients with a mean age of …

Coronary Steal Syndrome After Coronary Artery Bypass For Anomalous Aortic Origin Of A Coronary Artery., Benjamin A. Youdelman, Glenn J. Pelletier, C Igor Mesia, Marshall L. Jacobs

Department of Surgery Faculty Papers

Anomalous aortic origin of a coronary artery found in a symptomatic 9-year-old boy was initially treated with coronary artery bypass grafting using a left internal mammary artery anastomoses to the left anterior descending coronary artery, but resulted in coronary ischemia, likely from a steal phenomenon. Subsequent transection of the proximal left internal mammary artery with anastomosis to the ascending aorta, and coronary ostial enlargement, resulted in a durable treatment. We recommend caution in choosing coronary artery bypass grafting using a left internal mammary artery pedicle graft for the treatment of anomalous aortic origin of a coronary artery.

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: …

Transperitoneal Robotic-Assisted Laparoscopic Prostatectomy After Prosthetic Mesh Herniorrhaphy., Costas D. Lallas, Mark L. Pe, Jitesh V. Patel, Pranav Sharma, Leonard G. Gomella, Edouard J. Trabulsi

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: We report our institutional experience performing transperitoneal robotic-assisted laparoscopic prostatectomy (RALP) in patients with prior prosthetic mesh herniorrhaphy to assess the feasibility of this procedure in this patient population. METHODS: From October 2005 to January 2008, transperitoneal robotic-assisted laparoscopic prostatectomies were performed and prospectively recorded. We retrospectively reviewed 309 patients. RESULTS: Twenty-seven patients (8.7%) were found to have a history of prior hernia repair with prosthetic mesh placement. The mean age was 55.7, estimated blood loss (EBL) was 228 mL, operative (console) time was 197 minutes, and length of hospital stay (LOS) was 1.62 days. In contrast, …

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.

Discovering The Complexities Of Adolescent Compliance To Treatment, Megan Song, Hatim A. Omar

Pediatrics Faculty Publications

To explore the challenges faced in enhancing adolescent treatment compliance and to understand the roles of key players in this endeavor: the adolescent, parent and healthcare provider. Obtaining compliance from adolescents requires collaboration from the adolescent, caregiver and provider and depends on well-established relationships between each person in the triad: adolescent-provider, adolescent-caregiver, and caregiver-provider. Ensuring and improving adherence to treatment by adolescents is a challenging task but crucial to overall health outcomes. It requires the collaboration of the adolescent, parent and physician to create the optimal treatment plan, specifically tailored to the adolescent. For the clinician, maintaining good communication and …

Trends In Mental Health Of An Adolescent Medicine Clinic Patient Population, Abdel Salous, Linah Al-Alem, Hatim A. Omar

Pediatrics Faculty Publications

The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this paper was to identify mental health problems in an adolescent medicine clinic population in Lexington, KY and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. Of the patient population, 68% were urban, whereas 32% were rural. In terms of gender, 40% of the patients were male and 60% were female, 80% …

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 …

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Remission And Recovery In The Treatment For Adolescents With Depression Study (Tads): Acute And Long-Term Outcomes., Betsy D. Kennard, Susan G. Silva, Simon Tonev, Paul Rohde, Jennifer L. Hughes, Benedetto Vitiello, Christopher J. Kratochvil, John F. Curry, Graham J. Emslie, Mark Reinecke, John March

Journal Articles: Psychiatry

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).

METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined …

Atorvastatin May Have No Effect On Acute Phase Reaction In Children After Intravenous Bisphosphonate Infusion., Tarak Srivastava, Connie J. Haney, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Intravenous bisphosphonate therapy is associated with acute phase reaction characterized by fever and musculoskeletal pain. Bisphosphonates have been shown in vitro to activate gammadeltaT-cells to proliferate and produce cytokines, suggesting a role in acute phase reaction, which can be effectively blocked by statins. We conducted a double-blind randomized crossover placebo controlled study in 12 children (12.1 +/- 4.2 yr; 10 girls and 2 boys) receiving intravenous bisphosphonates to evaluate whether statins can be used to prevent acute phase reaction associated with therapy. Children received two cycles given 3-4 mo apart of intravenous bisphosphonate given on 2 consecutive days in each …

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

High-Resolution Analysis Of Dna Copy Number Alterations In Patients With Primary Open-Angle Glaucoma., Khaled K Abu-Amero, Ali Hellani, Patrick Bender, George L. Spaeth, Jonathan Myers, L Jay Katz, Marlene Moster, Thomas M Bosley

Wills Eye Hospital Papers

PURPOSE: To determine whether patients with isolated primary open-angle glaucoma (POAG) have evidence of chromosomal copy number alterations.

METHODS: Twenty-seven Caucasian and African-American POAG patients and 12 ethnically matched controls were carefully screened for possible glaucoma and tested for chromosomal copy number alterations using high resolution array comparative genomic hybridization.

RESULTS: No POAG patient had evidence of chromosomal copy number alterations when compared to normal ethnically matched controls. Additionally, there was no evidence of somatic mosaicism in any tested POAG patient.

CONCLUSIONS: Chromosomal deletions and/or duplications were not detected in POAG patients as compared to controls. Other chromosomal imbalances such …

Thoracoscopic Decortication Vs Tube Thoracostomy With Fibrinolysis For Empyema In Children: A Prospective, Randomized Trial., Shawn D. St Peter, Kuojen Tsao, Troy L. Spilde, Scott J. Keckler, Christopher J. Harrison, Mary Anne Jackson, Susan W. Sharp, Walter S. Andrews, Douglas C. Rivard, Frank P. Morello, G W. Holcomb Iii, Daniel J. Ostlie

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Management of empyema has been debated in the literature for decades. Although both primary video-assisted thoracoscopic surgery (VATS) and tube thoracostomy with pleural instillation of fibrinolytics have been shown to result in early resolution when compared to tube thoracostomy alone, there is a lack of comparative data between these modes of management. Therefore, we conducted a prospective, randomized trial comparing VATS to fibrinolytic therapy in children with empyema.

METHODS: After Institutional Review Board approval, children defined as having empyema by either loculation on imaging or more than 10,000 white blood cells/microL were treated with VATS or fibrinolysis. Based on …

Microrna Expression Profiling Of Male Breast Cancer., Matteo Fassan, Raffaele Baffa, Juan P Palazzo, Joshua Lloyd, Marco Crosariol, Chang-Gong Liu, Stefano Volinia, Hannes Alder, Massimo Rugge, Carlo M Croce, Anne Rosenberg

Department of Urology Faculty Papers

INTRODUCTION : MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers. METHODS : Paraffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast …

Hematologic Effects Of Placental Pathology On Very Low Birthweight Infants Born To Mothers With Preeclampsia., Kelly J. Zook, Md, Amy B. Mackley, Rnc, Jennifer Kern, David A. Paul. Md

Department of Pediatrics Faculty Papers

OBJECTIVE: To investigate the effect of placental pathology on neonatal neutrophils, platelets, hematocrit and nucleated red blood cells in very low birthweight (VLBW) infants born to mothers with preeclampsia. STUDY DESIGN: Retrospective cohort study of infants with birthweight < 1500 g born to mothers with preeclampsia from july, 2002 to july, 2006 at a single level III neonatal intensive care unit. Placental pathology was reviewed for the presence of placental infarction and vasculopathy. Hematologic parameters from day of life 0, 1 and 2 were obtained. Statistical analysis included repeated-measures analysis of variance and multivariable analysis using logistic regression. RESULT: The study sample included 203 infants with estimated gestational age of 28+/-3 weeks; 45% had placental infarctions and 26% placental vasculopathy. Infants with neutropenia and thrombocytopenia did not have an increased occurrence of placental infarction or maternal vasculopathy but were more likely to be of small gestational age (SGA) and of lower gestational age compared with infants without neutropenia or thrombocytopenia. After multivariable analysis, gestational age and SGA remained associated with both neutropenia and thrombocytopenia whereas placental infarction and vasculopathy did not remain in the models. CONCLUSION: In our population of VLBW infants born to mothers with preeclampsia, placental pathology was common. There was no association of placental infarction or vasculopathy with neonatal neutropenia and thrombocytopenia. The data suggest that neonatal hematologic effects of maternal preeclampsia, if related to the placenta, are associated with factors other than placental histology.

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 …

Unusual Fibrosclerotic Lesion Of The Laryngotracheal Complex Presenting As Subglottic Stenosis., Douglas R. Johnston, Joseph M. Curry, Raphael Rubin, Marc R. Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

We present a case report that describes the pathology, presentation, and management complexities of an unusual, destructive fibrosclerotic lesion of the laryngotracheal complex. An otherwise healthy 21-year-old man presented with a 1-year history of progressive shortness of breath and stridor. The initial examination revealed a 3-cm, grade III subglottic stenosis. Nodular fibrosis of the strap muscles, laryngotracheal cartilages, and trachea was evident. Biopsies revealed dense peritracheal desmoplastic reaction with focal erosion of cartilage. However, features diagnostic for relapsing polychondritis, desmoid tumor, or orbital pseudotumor were absent. The disease progressed to involve severe stenosis and thickening of the trachea and main …

Malignant Melanoma Metastatic To The Thyroid Gland: A Case Report And Review Of The Literature., Brian Kung, Md, Saba Aftab, Bs, Moira D. Wood, Md, David Rosen, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

The thyroid gland is a relatively uncommon site for a secondary malignancy; even less common is a case of malignant melanoma metastatic to the thyroid. We describe the case of a 68-year-old man who presented with a neck mass in the posterior triangle. Fine-needle aspiration biopsy (FNAB) identified the mass as a malignant melanoma. The patient had had no known primary skin melanoma. He underwent a left modified radical neck dissection, and the mass was discovered to be a positive lymph node. Postoperatively, he declined to undergo radio- and chemotherapy. Eighteen months later, he returned with a diffusely enlarged thyroid. …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Isolated Polyethylene Exchange Versus Acetabular Revision For Polyethylene Wear, Camilo Restrepo, Elie Ghanem, Carrie Houssock, Mathew Austin, Javad Parvizi, William J. Hozack

Department of Orthopaedic Surgery Faculty Papers

Polyethylene wear and osteolysis are not uncommon in THA mid- and long-term. In asymptomatic patients the dilemma faced by the orthopaedic surgeon is whether to revise the cup and risk damage to the supporting columns and even pelvic discontinuity or to perform isolated polyethylene exchange and risk a high rate of postoperative recurrent instability and dislocation that will necessitate further surgery. We retrospectively reviewed 62 patients (67 hips) who underwent revision arthroplasty for polywear and osteolysis. Thirty-six hips had isolated polyethylene exchange, while 31 had full acetabular revision. The minimum followup was 2 years (mean, 2.8 years; range, 2-5 years). …