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Outcome Of Blunt Thoracic Aortic Injury In A Level I Trauma Center: An 8-Year Review., E J Frick, M D Cipolle, Michael D. Pasquale Md, Facs, Fccm, T E Wasser, M Rhodes, Raymond L. Singer Md, S A Nastasee May 2016

Outcome Of Blunt Thoracic Aortic Injury In A Level I Trauma Center: An 8-Year Review., E J Frick, M D Cipolle, Michael D. Pasquale Md, Facs, Fccm, T E Wasser, M Rhodes, Raymond L. Singer Md, S A Nastasee

Michael D Pasquale MD, FACS, FCCM

BACKGROUND: The purpose of this study was to evaluate our experience with blunt thoracic aortic injury and identify factors predictive of outcome.

METHODS: Hospital charts, trauma registry data, and autopsies of 64 patients with blunt thoracic aortic injury from 1988 to 1995 were reviewed.

RESULTS: Patients were identified and segregated based on admission physiology. Group 1 patients (n = 19) arrived in arrest. Group 2 patients (n = 10) arrived in shock with systolic BP 90. Group 3 patients (n = 35) arrived with systolic BP>90. All patients in groups 1 and 2 expired. Injury Severity Scores for nonsurvivors …


Acute Interstitial Nephritis Associated With Iga Nephropathy In Children., Sanjeev Vasishtha, B Gauthier, E Valderrama, H Trachtman Sep 2015

Acute Interstitial Nephritis Associated With Iga Nephropathy In Children., Sanjeev Vasishtha, B Gauthier, E Valderrama, H Trachtman

Sanjeev Vasishtha MD

IgA nephropathy (IgAN) is a relatively common glomerulopathy in children and adolescents. The etiology of this disease is uncertain. We previously reported a child with IgAN who developed acute interstitial nephritis. We now describe three pediatric patients, including the index case, who had IgAN and who developed concomitant acute interstitial nephritis in association with renal functional impairment. We suggest that this histopathological lesion be considered in any child with IgAN and unexpectedly severe kidney dysfunction.


Nephrotic Syndrome As The Initial Manifestation Of Acquired Immunodeficiency Syndrome., Sanjeev Vasishtha, H Trachtman, B Gauthier, E Valderrama Sep 2015

Nephrotic Syndrome As The Initial Manifestation Of Acquired Immunodeficiency Syndrome., Sanjeev Vasishtha, H Trachtman, B Gauthier, E Valderrama

Sanjeev Vasishtha MD

No abstract provided.


Emergence Of Candida Parapsilosis As The Predominant Species Causing Candidemia In Children., I Levy, L G Rubin, Sanjeev Vasishtha, V Tucci, S K Sood Sep 2015

Emergence Of Candida Parapsilosis As The Predominant Species Causing Candidemia In Children., I Levy, L G Rubin, Sanjeev Vasishtha, V Tucci, S K Sood

Sanjeev Vasishtha MD

An increase in the rate of isolation of Candida parapsilosis, relative to other Candida species, in our children's hospital led us to analyze the clinical and epidemiological variables associated with candidemia. We sought to determine if these variables are different for patients infected with C. parapsilosis. All episodes of candidemia occurring over a 7-year period were analyzed retrospectively. Of 81 episodes in 80 patients, 35 (43%) were in neonates, and 46 (57%) were in nonneonates. C. parapsilosis was isolated in 40 episodes (49%). C. parapsilosis was significantly more likely than non-C. parapsilosis species to be associated with prematurity (P = …


Gemella Morbillorum As A Cause Of Septic Shock., Sanjeev Vasishtha, H D Isenberg, S K Sood Sep 2015

Gemella Morbillorum As A Cause Of Septic Shock., Sanjeev Vasishtha, H D Isenberg, S K Sood

Sanjeev Vasishtha MD

The gram-positive bacterium Gemella morbillorum has been recovered from patients with endocarditis but has rarely been associated with acute fulminant infections. We describe two children with a rapid onset of septic shock, which was fatal in one, following infection with this organism. G. morbillorum is a commensal organism of the upper respiratory tract; it gained access to the bloodstreams in these patients, and bacteremia occurred. A clinical drawback is that the initial colonial morphology of this organism leads to presumptive identification as a viridans streptococcus, an organism not commonly associated with septic shock syndrome. Resistance of G. morbillorum to penicillin …


Outcome Of Blunt Thoracic Aortic Injury In A Level I Trauma Center: An 8-Year Review., E J Frick, M D Cipolle, Michael Pasquale, T E Wasser, M Rhodes, Raymond Singer, S A Nastasee Sep 2015

Outcome Of Blunt Thoracic Aortic Injury In A Level I Trauma Center: An 8-Year Review., E J Frick, M D Cipolle, Michael Pasquale, T E Wasser, M Rhodes, Raymond Singer, S A Nastasee

Raymond L Singer MD

BACKGROUND: The purpose of this study was to evaluate our experience with blunt thoracic aortic injury and identify factors predictive of outcome. METHODS: Hospital charts, trauma registry data, and autopsies of 64 patients with blunt thoracic aortic injury from 1988 to 1995 were reviewed. RESULTS: Patients were identified and segregated based on admission physiology. Group 1 patients (n = 19) arrived in arrest. Group 2 patients (n = 10) arrived in shock with systolic BP 90. Group 3 patients (n = 35) arrived with systolic BP>90. All patients in groups 1 and 2 expired. Injury Severity Scores for nonsurvivors …


Clinical Clearance Of The Cervical Spine In Blunt Trauma Patients Younger Than 3 Years: A Multi-Center Study Of The American Association For The Surgery Of Trauma., Rafael Pieretti-Vanmarcke, George C Velmahos, Michael L Nance, Saleem Islam, Richard A Falcone, Paul W Wales, Rebeccah L Brown, Barbara A Gaines, Christine Mckenna, Forrest O Moore, Pamela W Goslar, Kenji Inaba, Galinos Barmparas, Eric R Scaife, Ryan R Metzger, Douglas L Brockmeyer, Jeffrey S Upperman, Joaquin Estrada, David A Lanning, Sara K Rasmussen, Paul D Danielson, Michael P Hirsh, Heitor F X Consani, Steven Stylianos, Candace Pineda, Scott H Norwood, Steven W Bruch, Robert Drongowski, Robert Barraco, Michael Pasquale, Farheen Hussain, Erwin F Hirsch, P Daniel Mcneely, Mary E Fallat, David S Foley, Joseph A Iocono, Heather M Bennett, Kenneth Waxman, Kelly Kam, Lisa Bakhos, Laurie Petrovick, Yuchiao Chang, Peter T Masiakos Aug 2015

Clinical Clearance Of The Cervical Spine In Blunt Trauma Patients Younger Than 3 Years: A Multi-Center Study Of The American Association For The Surgery Of Trauma., Rafael Pieretti-Vanmarcke, George C Velmahos, Michael L Nance, Saleem Islam, Richard A Falcone, Paul W Wales, Rebeccah L Brown, Barbara A Gaines, Christine Mckenna, Forrest O Moore, Pamela W Goslar, Kenji Inaba, Galinos Barmparas, Eric R Scaife, Ryan R Metzger, Douglas L Brockmeyer, Jeffrey S Upperman, Joaquin Estrada, David A Lanning, Sara K Rasmussen, Paul D Danielson, Michael P Hirsh, Heitor F X Consani, Steven Stylianos, Candace Pineda, Scott H Norwood, Steven W Bruch, Robert Drongowski, Robert Barraco, Michael Pasquale, Farheen Hussain, Erwin F Hirsch, P Daniel Mcneely, Mary E Fallat, David S Foley, Joseph A Iocono, Heather M Bennett, Kenneth Waxman, Kelly Kam, Lisa Bakhos, Laurie Petrovick, Yuchiao Chang, Peter T Masiakos

Michael D Pasquale MD, FACS, FCCM

BACKGROUND: Cervical spine clearance in the very young child is challenging. Radiographic imaging to diagnose cervical spine injuries (CSI) even in the absence of clinical findings is common, raising concerns about radiation exposure and imaging-related complications. We examined whether simple clinical criteria can be used to safely rule out CSI in patients younger than 3 years. METHODS: The trauma registries from 22 level I or II trauma centers were reviewed for the 10-year period (January 1995 to January 2005). Blunt trauma patients younger than 3 years were identified. The measured outcome was CSI. Independent predictors of CSI were identified by …


Atomoxetine Treatment In Children And Adolescents With Attention-Deficit Hyperactivity Disorder: What Are The Long-Term Health-Related Quality-Of-Life Outcomes?, Amy Perwien, Christopher Kratochvil, Douglas Faries, Brigette Vaughan, Thomas Spencer, Ronald Brown Aug 2015

Atomoxetine Treatment In Children And Adolescents With Attention-Deficit Hyperactivity Disorder: What Are The Long-Term Health-Related Quality-Of-Life Outcomes?, Amy Perwien, Christopher Kratochvil, Douglas Faries, Brigette Vaughan, Thomas Spencer, Ronald Brown

Ronald Brown

OBJECTIVE: Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) in children. However, relatively few studies have addressed the impact of treatment on long-term subjective, psychosocial outcomes, such as health-related quality of life (HRQL). This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD. METHODS: Participants included 6- to 17-year-old children and adolescents (n = 912) with ADHD enrolled in a 24-month, multicenter, open-label trial of atomoxetine. Outcomes included clinician ratings of ADHD, parent ratings of ADHD, and a widely used measure of HRQL (The Child Health …


Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj Jul 2015

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Sharone Green

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …


Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser Jun 2015

Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser

Mary M. Lee

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to …


Association Between Chlorinated Pesticides In The Serum Of Prepubertal Russian Boys And Longitudinal Biomarkers Of Metabolic Function, Jane Burns, Paige Williams, Susan Korrick, Russ Hauser, Oleg Sergeyev, Boris Revich, Thuy Lam, Mary Lee Jun 2015

Association Between Chlorinated Pesticides In The Serum Of Prepubertal Russian Boys And Longitudinal Biomarkers Of Metabolic Function, Jane Burns, Paige Williams, Susan Korrick, Russ Hauser, Oleg Sergeyev, Boris Revich, Thuy Lam, Mary Lee

Mary M. Lee

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, beta-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass …


Hydrofiber Dressing With Silver For The Management Of Split-Thickness Donor Sites: A Randomized Evaluation Of Two Protocols Of Care, Sigrid Blome-Eberwein, R Johnson, Sidney Miller, Daniel Caruso, Marion Jordan, Stephen Milner, Edward Tredget, Kevin Sittig, Leslie Smith Apr 2015

Hydrofiber Dressing With Silver For The Management Of Split-Thickness Donor Sites: A Randomized Evaluation Of Two Protocols Of Care, Sigrid Blome-Eberwein, R Johnson, Sidney Miller, Daniel Caruso, Marion Jordan, Stephen Milner, Edward Tredget, Kevin Sittig, Leslie Smith

Sigrid A Blome-Eberwein MD

BACKGROUND: This randomized, open-label study evaluated Aquacel Ag Hydrofiber dressing with silver (HDS; ConvaTec, Skillman, NJ, USA) with an adherent or gelled protocol in the management of split-thickness donor sites. METHODS: HDS was the primary dressing in the adherent group (gauze as secondary covering) and gelled group (transparent film as secondary covering). Dressings were changed on study day 1 or 2 and study days 5 (optional), 10 (optional), and 14. The primary outcome was healing (>or=90% re-epithelialization) at study day 14. RESULTS: Seventy subjects were treated (36 adherent, 34 gelled). By study day 14, 77% of donor sites had …


Clinical Clearance Of The Cervical Spine In Blunt Trauma Patients Younger Than 3 Years: A Multi-Center Study Of The American Association For The Surgery Of Trauma., Rafael Pieretti-Vanmarcke, George C Velmahos, Michael L Nance, Saleem Islam, Richard A Falcone, Paul W Wales, Rebeccah L Brown, Barbara A Gaines, Christine Mckenna, Forrest O Moore, Pamela W Goslar, Kenji Inaba, Galinos Barmparas, Eric R Scaife, Ryan R Metzger, Douglas L Brockmeyer, Jeffrey S Upperman, Joaquin Estrada, David A Lanning, Sara K Rasmussen, Paul D Danielson, Michael P Hirsh, Heitor F X Consani, Steven Stylianos, Candace Pineda, Scott H Norwood, Steven W Bruch, Robert Drongowski, Robert Barraco, Michael Pasquale, Farheen Hussain, Erwin F Hirsch, P Daniel Mcneely, Mary E Fallat, David S Foley, Joseph A Iocono, Heather M Bennett, Kenneth Waxman, Kelly Kam, Lisa Bakhos, Laurie Petrovick, Yuchiao Chang, Peter T Masiakos Mar 2015

Clinical Clearance Of The Cervical Spine In Blunt Trauma Patients Younger Than 3 Years: A Multi-Center Study Of The American Association For The Surgery Of Trauma., Rafael Pieretti-Vanmarcke, George C Velmahos, Michael L Nance, Saleem Islam, Richard A Falcone, Paul W Wales, Rebeccah L Brown, Barbara A Gaines, Christine Mckenna, Forrest O Moore, Pamela W Goslar, Kenji Inaba, Galinos Barmparas, Eric R Scaife, Ryan R Metzger, Douglas L Brockmeyer, Jeffrey S Upperman, Joaquin Estrada, David A Lanning, Sara K Rasmussen, Paul D Danielson, Michael P Hirsh, Heitor F X Consani, Steven Stylianos, Candace Pineda, Scott H Norwood, Steven W Bruch, Robert Drongowski, Robert Barraco, Michael Pasquale, Farheen Hussain, Erwin F Hirsch, P Daniel Mcneely, Mary E Fallat, David S Foley, Joseph A Iocono, Heather M Bennett, Kenneth Waxman, Kelly Kam, Lisa Bakhos, Laurie Petrovick, Yuchiao Chang, Peter T Masiakos

Robert D Barraco MD, MPH

BACKGROUND: Cervical spine clearance in the very young child is challenging. Radiographic imaging to diagnose cervical spine injuries (CSI) even in the absence of clinical findings is common, raising concerns about radiation exposure and imaging-related complications. We examined whether simple clinical criteria can be used to safely rule out CSI in patients younger than 3 years. METHODS: The trauma registries from 22 level I or II trauma centers were reviewed for the 10-year period (January 1995 to January 2005). Blunt trauma patients younger than 3 years were identified. The measured outcome was CSI. Independent predictors of CSI were identified by …


Deaf Students And Their Classroom Communication: An Evaluation Of Higher Order Categorical Interactions Among School And Background Characteristics, Thomas Allen, Melissa Anderson Jan 2015

Deaf Students And Their Classroom Communication: An Evaluation Of Higher Order Categorical Interactions Among School And Background Characteristics, Thomas Allen, Melissa Anderson

Melissa L. Anderson

This article investigated to what extent age, use of a cochlear implant, parental hearing status, and use of sign in the home determine language of instruction for profoundly deaf children. Categorical data from 8,325 profoundly deaf students from the 2008 Annual Survey of Deaf and Hard-of-Hearing Children and Youth were analyzed using chi-square automated interaction detector, a stepwise analytic procedure that allows the assessment of higher order interactions among categorical variables. Results indicated that all characteristics were significantly related to classroom communication modality. Although younger and older students demonstrated a different distribution of communication modality, for both younger and older …


Evaluation Of Short And Tall Stature In Children, Benjamin Nwosu, Mary Lee Sep 2014

Evaluation Of Short And Tall Stature In Children, Benjamin Nwosu, Mary Lee

Mary M. Lee

Children and adolescents whose heights and growth velocities deviate from the normal percentiles on standard growth charts present a special challenge to physicians. Height that is less than the 3rd percentile or greater than the 97th percentile is deemed short or tall stature, respectively. A growth velocity outside the 25th to 75th percentile range may be considered abnormal. Serial height measurements over time documented on a growth chart are key in identifying abnormal growth. Short or tall stature is usually caused by variants of a normal growth pattern, although some patients may have serious underlying pathologies. A comprehensive history and …


Social Support To Empower Parents (Step): An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Susan Sullivan-Bolyai, Carol Bova, Katherine Leung, Allison Trudeau, Mary Lee, Philip Gruppuso Sep 2014

Social Support To Empower Parents (Step): An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Susan Sullivan-Bolyai, Carol Bova, Katherine Leung, Allison Trudeau, Mary Lee, Philip Gruppuso

Mary M. Lee

PURPOSE: The purpose of this study was to test the efficacy of a social support intervention with parents of children <13 years old newly diagnosed with type 1 diabetes mellitus>(T1DM).

METHODS: For this randomized, controlled clinical trial, 10 parent mentors of children diagnosed with T1DM >or=1 year and 60 parent participants were recruited from 2 pediatric diabetes centers. Mentors were trained to provide social support (home visits and phone calls) for 12 months to families in the experimental arm (32 mothers). Control group parents (28 mothers) received the phone number of an experienced parent (not trained to give social support) to call as needed.

FINDINGS: Mothers in the experimental …


The Increased Incidence Of Congenital Hypothyroidism: Fact Or Fancy?, Marvin Mitchell, Ho-Wen Hsu, Inderneel Sahai, Stuart Brink, Laurie Cohen, Rosalind Brown, Roger Eaton, Mary Lee, Lynne Levitsky, Edward Reiter, Abdollah Sadeghi-Nejad, Leslie Soyka, Joseph Wolfsdorf Sep 2014

The Increased Incidence Of Congenital Hypothyroidism: Fact Or Fancy?, Marvin Mitchell, Ho-Wen Hsu, Inderneel Sahai, Stuart Brink, Laurie Cohen, Rosalind Brown, Roger Eaton, Mary Lee, Lynne Levitsky, Edward Reiter, Abdollah Sadeghi-Nejad, Leslie Soyka, Joseph Wolfsdorf

Mary M. Lee

OBJECTIVE: The incidence of congenital hypothyroidism (CH) detected by newborn screening in the US has increased significantly since the early 1990s. We defined the characteristics associated with the increased incidence. PATIENTS: A cohort of children with CH born during an earlier period of low incidence (1991-94) was compared with a cohort born during a later period when the incidence of CH had doubled (2001-04). MEASUREMENTS: Screening was performed with T4 as the primary marker and thyroid stimulating hormone (TSH) on selected specimens. Follow-up on hypothyroid children determined whether they had permanent or transient hypothyroidism. Cases were classified based on laboratory …


Evidence Of Insulin-Like Growth Factor Binding Protein-3 Proteolysis During Growth Hormone Stimulation Testing, Benjamin Nwosu, Leslie Soyka, Amanda Angelescu, Mary Lee Sep 2014

Evidence Of Insulin-Like Growth Factor Binding Protein-3 Proteolysis During Growth Hormone Stimulation Testing, Benjamin Nwosu, Leslie Soyka, Amanda Angelescu, Mary Lee

Mary M. Lee

OBJECTIVES: The ternary complex is composed of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and acid labile subunit (ALS). Growth hormone (GH) promotes IGFBP-3 proteolysis to release free IGF-I, ALS, and IGFBP-3 fragments. Our aim was to determine whether elevated GH levels during GH stimulation testing would trigger IGFBP-3 proteolysis. DESIGN: This prospective study of 10 short prepubertal children (height standard deviation score -2.37 +/- 0.31) used arginine and GH releasing hormone stimulation to study dynamic changes in the ternary complex moieties. IGFBP-3 was measured in two assays: a radioimmunoassay (RIA) that detects both cleaved and intact IGFBP-3; and …


Farm Residence And Reproductive Health Among Boys In Rural South Africa, Rene English, Melissa Perry, Mary Lee, Elaine Hoffman, Steven Delport, Mohamed Dalvie Sep 2014

Farm Residence And Reproductive Health Among Boys In Rural South Africa, Rene English, Melissa Perry, Mary Lee, Elaine Hoffman, Steven Delport, Mohamed Dalvie

Mary M. Lee

BACKGROUND: Few studies have investigated reproductive health effects of contemporary agricultural pesticides in boys. OBJECTIVES: To determine the association between pesticide exposure and reproductive health of boys. METHODS: We conducted a cross-sectional study in rural South Africa of boys living on and off farms. The study included a questionnaire (demographics, general and reproductive health, phyto-estrogen intake, residential history, pesticide exposures, exposures during pregnancy); and a physical examination that included sexual maturity development ratings; testicular volume; height, weight, body mass index; and sex hormone concentrations. RESULTS: Among the 269 boys recruited into the study, 177 (65.8%) were categorized as farm (high …


Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman Aug 2014

Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Alan Rothman

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …


Intracellular Cytokine Production By Dengue Virus-Specific T Cells Correlates With Subclinical Secondary Infection, Steven Hatch, Timothy Endy, Stephen Thomas, Anuja Mathew, James Potts, Pamela Pazoles, Daniel Libraty, Robert Gibbons, Alan Rothman Aug 2014

Intracellular Cytokine Production By Dengue Virus-Specific T Cells Correlates With Subclinical Secondary Infection, Steven Hatch, Timothy Endy, Stephen Thomas, Anuja Mathew, James Potts, Pamela Pazoles, Daniel Libraty, Robert Gibbons, Alan Rothman

Alan Rothman

The pathophysiology of dengue virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6-11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4(+) and CD8(+) cells in response to stimulation with dengue antigen. We found higher frequencies of dengue virus-specific TNFalpha, IFNgamma-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with …


T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman Aug 2014

T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman

Alan Rothman

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF …


Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy Endy, Kathryn Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan Rothman, Stephen Thomas, Richard Jarman, Daniel Libraty, Robert Gibbons Aug 2014

Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy Endy, Kathryn Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan Rothman, Stephen Thomas, Richard Jarman, Daniel Libraty, Robert Gibbons

Alan Rothman

BACKGROUND: Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection.

METHODOLOGY/PRINCIPAL FINDINGS: In a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our …


T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan Gagnon, Anita Leporati, Sharone Green, Siripen Kalayanarooj, David Vaughn, Henry Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis Ennis, Alan Rothman Aug 2014

T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan Gagnon, Anita Leporati, Sharone Green, Siripen Kalayanarooj, David Vaughn, Henry Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis Ennis, Alan Rothman

Alan Rothman

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences …


Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman Aug 2014

Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Alan Rothman

Plasma leakage in dengue hemorrhagic fever (DHF) is associated with elevated plasma levels of cytokines. To define further the contribution of immune activation to DHF and the source of cytokines, we analyzed the production of cytokines in peripheral blood mononuclear cells (PBMC) obtained from children with dengue, using RT-PCR and immunostaining. Tumor necrosis factor-alpha (TNF-alpha) and TNF-beta expression was detected in all samples by PCR and in < 50% of samples by immunostaining. Interferon-gamma (IFN-gamma) expression was detected in < 50% of samples by either method. Interleukin-2 (IL-2) and IL-4 expression was detected in a few samples by immunostaining but was not …


Clinical And Laboratory Features That Distinguish Dengue From Other Febrile Illnesses In Endemic Populations, James Potts, Alan Rothman Aug 2014

Clinical And Laboratory Features That Distinguish Dengue From Other Febrile Illnesses In Endemic Populations, James Potts, Alan Rothman

Alan Rothman

OBJECTIVE: Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue haemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHOD: Systematic review of the literature from 1990 to 30 October 2007 including English publications comparing dengue and OFI. RESULTS: Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children …


Virus-Induced Decline In Soluble Vascular Endothelial Growth Receptor 2 Is Associated With Plasma Leakage In Dengue Hemorrhagic Fever, Anon Srikiatkhachorn, Chuanpis Ajariyakhajorn, Timothy Endy, Siripen Kalayanarooj, Daniel Libraty, Sharone Green, Francis Ennis, Alan Rothman Aug 2014

Virus-Induced Decline In Soluble Vascular Endothelial Growth Receptor 2 Is Associated With Plasma Leakage In Dengue Hemorrhagic Fever, Anon Srikiatkhachorn, Chuanpis Ajariyakhajorn, Timothy Endy, Siripen Kalayanarooj, Daniel Libraty, Sharone Green, Francis Ennis, Alan Rothman

Alan Rothman

Some individuals infected with dengue virus develop dengue hemorrhagic fever (DHF), a viral hemorrhagic disease characterized by a transient period of localized plasma leakage. To determine the importance of vascular endothelial growth factor A (VEGF-A) in this syndrome, we compared plasma levels of VEGF-A and the soluble forms of its receptors in patients with DHF to patients with dengue fever (DF), a milder form of dengue virus infection without plasma leakage. We observed a rise in the plasma levels of free, but not total VEGF-A in DHF patients at the time of plasma leakage. This was associated with a decline …


Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj Aug 2014

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Alan Rothman

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …


Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman Aug 2014

Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman

Alan Rothman

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA …


B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman Aug 2014

B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman

Alan Rothman

Low-avidity serotype-cross-reactive antibodies are hypothesized to play a key role in triggering severe disease in patients with secondary dengue virus (DENV) infection. However, there is little systematic information about the frequency, avidity, and cross-reactivity of DENV-specific B cells in individuals experiencing primary instead of secondary infection. We compared DENV-specific B-cell responses in a cohort of Thai children with primary or secondary DENV infection. B cells specific for DENV precursor membrane protein, envelope (E) protein, and nonstructural protein 1 were detectable in immune peripheral blood mononuclear cells with the highest frequencies of DENV E-specific B cells detected in patients experiencing primary …