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Now showing items 1 - 16 of 297

  • The Brief Case: Too Beta To Be a "B"

    Gullett, Jonathan C.   Westblade, Lars F.   Green, Daniel A.   Whittier, Susan   Burd, Eileen M.  

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  • Mechanisms of Intestinal Barrier Dysfunction in Sepsis

    Yoseph, Benyam P.   Klingensmith, Nathan J.   Liang, Zhe   Breed, Elise R.   Burd, Eileen M.   Mittal, Rohit   Dominguez, Jessica A.   Petrie, Benjamin   Ford, Mandy L.   Coopersmith, Craig M.  

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis induce a significant increase in intestinal permeability mediated through a common pathway involving alterations in claudin 2, claudin 5, JAM-A, and occludin although model-specific differences in ZO-1 were also identified.
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  • Human Papillomavirus Laboratory Testing: the Changing Paradigm

    Burd, Eileen M.  

    High-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing.
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  • Answer to November 2015 Photo Quiz

    Burd, Eileen M.   Rebolledo, Paulina A.   Bourbeau, P.  

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  • Ebola Virus: a Clear and Present Danger

    Burd, Eileen M.   Doern, G. V.  

    An epidemic of Ebola virus disease is occurring in Western Africa on a scale not seen before, particularly in the countries of Guinea, Liberia, and Sierra Leone. The continued spread is facilitated by insufficient medical facilities, poor sanitation, travel, and unsafe burial practices. Several patients diagnosed with Ebola virus disease in Africa have been evacuated to the United States for treatment, and several other patients have been diagnosed in the United States. It is important for laboratories to be aware of available tests, especially those granted emergency use authorization, as hospitals prepare protocols for the diagnosis and management of high-risk patients.
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  • Photo Quiz: Thigh Abscess in a Morbidly Obese Diabetic Patient: FIG 1

    Burd, Eileen M.   Rebolledo, Paulina A.   Bourbeau, P.  

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  • Bacteremia in a Patient with Hepatic Encephalopathy

    Hinrichs, Benjamin H.   Jerris, Robert C.   Burd, Eileen M.  

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  • Unusual Empyema Pseudozyma aphidis

    Guarner, Jeannette   Burd, Eileen M.   Williams, Teresa C.   Jerris, Robert   del Rio, Carlos  

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  • A 36-Year-Old with Recurrent Conjunctivitis

    Burd, Eileen M.   Sharp, Susan E.  

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  • Evaluation of an Online Program To Teach Microbiology to Internal Medicine Residents

    Guarner, Jeannette   Burd, Eileen M.   Kraft, Colleen S.   Armstrong, Wendy S.   Lenorr, Kenya   Spicer, Jennifer O.   Martin, Donna   del Rio, Carlos  

    Microbiology rounds are an integral part of infectious disease consultation service. During microbiology rounds, we highlight microbiology principles using vignettes. We created case-based, interactive, microbiology online modules similar to the vignettes presented during microbiology rounds. Since internal medicine residents rotating on our infectious disease elective have limited time to participate in rounds and learn microbiology, our objective was to evaluate the use of the microbiology online modules by internal medicine residents. We asked residents to complete 10 of 25 online modules during their infectious disease elective. We evaluated which modules they chose and the change in their knowledge level. Forty-six internal medicine residents completed assessments given before and after accessing the modules with an average of 11/20 (range, 6 to 19) and 16/20 (range, 9 to 20) correct questions, respectively (average improvement, 5 questions; P =3D 0.0001). The modules accessed by more than 30 residents included those related to Clostridium difficile, anaerobes, Candida spp., Streptococcus pneumoniae, influenza, Mycobacterium tuberculosis, and Neisseria meningitidis. We demonstrated improved microbiology knowledge after completion of the online modules. This improvement may not be solely attributed to completing the online modules, as fellows and faculty may have provided additional microbiology education during the rotation.
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  • A 53-Year-Old Stem Cell Transplant Recipient with Meningitis and Bacteremia

    Johnson, Hunter   Burd, Eileen M.   Sharp, Susan E.  

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  • Acute Cholecystitis Caused by Nontoxigenic Vibrio cholerae O1 Inaba

    Vogt, Adam P.   Doshi, Rupali K.   Higgins, Judy E.   Burd, Eileen M.   Ribner, Bruce S.   Kraft, Colleen S.  

    A rare case of acute cholecystitis caused by serogroup O1 Vibrio cholerae in an 83-year-old man is presented. His risk factors for cholecystitis included advanced age and previous abdominal surgeries. The patient had consumed raw oysters several days before presentation. The patient had a poor outcome after admission for this infection, likely due to his underlying illnesses that complicated his hospital course.
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  • Validation of Laboratory-Developed Molecular Assays for Infectious Diseases

    Burd, Eileen M.  

    Molecular technology has changed the way that clinical laboratories diagnose and manage many infectious diseases. Excellent sensitivity, specificity, and speed have made molecular assays an attractive alternative to culture or enzyme immunoassay methods. Many molecular assays are commercially available and FDA approved. Others, especially those that test for less common analytes, are often laboratory developed. Laboratories also often modify FDA-approved assays to include different extraction systems or additional specimen types. The Clinical Laboratory Improvement Amendments (CLIA) federal regulatory standards require clinical laboratories to establish and document their own performance specifications for laboratory-developed tests to ensure accurate and precise results prior to implementation of the test. The performance characteristics that must be established include accuracy, precision, reportable range, reference interval, analytical sensitivity, and analytical specificity. Clinical laboratories are challenged to understand the requirements and determine the types of experiments and analyses necessary to meet the requirements. A variety of protocols and guidelines are available in various texts and documents. Many of the guidelines are general and more appropriate for assays in chemistry sections of the laboratory but are applied in principle to molecular assays. This review presents information that laboratories may consider in their efforts to meet regulatory requirements.
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  • Prevention of Lymphocyte Apoptosis in Septic Mice with Cancer Increases Mortality

    Fox, Amy C.   Breed, Elise R.   Liang, Zhe   Clark, Andrew T.   Zee-Cheng, Brendan R.   Chang, Katherine C.   Dominguez, Jessica A.   Jung, Enjae   Dunne, W. Michael   Burd, Eileen M.   Farris, Alton B.   Linehan, David C.   Coopersmith, Craig M.  

    Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-alpha and IFN-gamma in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia. The Journal of Immunology, 2011, 187: 1950-1956.
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  • Caspase-8 Collaborates with Caspase-11 to Drive Tissue Damage and Execution of Endotoxic Shock

    Manda, Pratyusha   Feng, Yanjun   Lyons, John D.   Berger, Scott B.   Otani, Shunsuke   DeLaney, Alexandra   Tharp, Gregory K.   Maner-Smith, Kristal   Burd, Eileen M.   Schaeffer, Michelle   Hoffman, Sandra   Capriotti, Carol   Roback, Linda   Young, Cedrick B.   Liang, Zhe   Ortlund, Eric A.   DiPaolo, Nelson C.   Bosinger, Steven   Bertin, John   Gough, Peter J.   Brodsky, Igor E.   Coopersmith, Craig M.   Shayakhmetov, Dmitry M.   Mocarski, Edward S.  

    The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin D. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate shock without any contribution from cas pase-8 or caspase-11. Both proteases had to be present to support tumor necrosis factor- and interferon-beta-dependent tissue injury first observed in the small intestine and later in spleen and thymus. Caspase-11 enhanced the activation of caspase-8 and extrinsic cell death machinery within the lower small intestine. Neither caspase-8 nor caspase-11 was individually sufficient for shock. Both caspases collaborated to amplify inflammatory signals associated with tissue damage. Therefore, combined pyroptotic and apoptotic signaling mediated endotoxemia independently of RIPK1 kinase activity and RIPK3 function. These observations bring to light the relevance of tissue compartmentalization to disease processes in vivo where cytokines act in parallel to execute diverse cell death pathways.
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  • Pustular dermatitis caused by Dermatophilus congolensis

    Burd, Eileen M.   Juzych, Lydia A.   Rudrik, James T.   Habib, Fadi  

    We describe a case of pustular dermatitis in a 15-year-old girl who had just returned from horseback riding camp. Based on gram staining, colony characteristics, biochemical reactions, and whole-cell fatty acid analysis, the causative agent was identified as Dermatophilus congolensis. The literature contains few reports of human infection with this organism.
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