Biomedical subjects

Leona W Ayers

Publications and source records attributed to Leona W Ayers.

10 recordsLinked to original sources

PubMed2006

Bacterial lipopolysaccharide enhances cardiac dysfunction but not retroviral replication in murine AIDS: roles of macrophage infiltration and toll-like receptor 4 expression.

Cardiovascular disease is an important complication of human immunodeficiency virus/acquired immune deficiency syndrome (AIDS), but the mechanism(s) involved are poorly understood. Although co-infecting pathogens have been implicated as an important factor in AIDS progression, no studies have investigated these interactions in cardiac tissue. We recently demonstrated that the murine AIDS model (LPBM5 retroviral infection) mimics human immunodeficiency virus-related cardiac dysfunction and pathology. We tested the hypothesis that subseptic lipopolysaccharide exposure (LPS) would enhance LPBM5 progression and exacerbate cardiovascular dysfunction during murine AIDS development. LPS (5 mg/kg, Escherichia coli 0111:B4) was administered at 1, 6, and 8 weeks during LPBM5 infection, and cardiac performance was evaluated at 10 weeks using noninvasive echocardiography. LPS alone had no significant effects, whereas it amplified abnormalities in cardiac structure and function observed in murine AIDS. Cardiac dysfunction was associated with selective increases in nonfocal infiltration of CD68(+) cells and correlated with the extent of cardiac dysfunction. Retroviral progression and cardiac retroviral content remained unaltered, but cardiac toll-like receptor 4 was increased in retrovirus + LPS. We provide first-time evidence of multipathogen enhancements to retrovirus-related cardiac complications and implicate innate immune responses, not co-pathogen-induced retroviral replication, as the primary mechanism in this setting.

Acquired Immunodeficiency Syndrome↗

PubMed2005

The tissue micro-array data exchange specification: a web based experience browsing imported data.

BACKGROUND: The AIDS and Cancer Specimen Resource (ACSR) is an HIV/AIDS tissue bank consortium sponsored by the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis (DCTD). The ACSR offers to approved researchers HIV infected biologic samples and uninfected control tissues including tissue cores in micro-arrays (TMA) accompanied by de-identified clinical data. Researchers interested in the type and quality of TMA tissue cores and the associated clinical data need an efficient method for viewing available TMA materials. Because each of the tissue samples within a TMA has separate data including a core tissue digital image and clinical data, an organized, standard approach to producing, navigating and publishing such data is necessary. The Association for Pathology Informatics (API) extensible mark-up language (XML) TMA data exchange specification (TMA DES) proposed in April 2003 provides a common format for TMA data. Exporting TMA data into the proposed format offers an opportunity to implement the API TMA DES. Using our public BrowseTMA tool, we created a web site that organizes and cross references TMA lists, digital "virtual slide" images, TMA DES export data, linked legends and clinical details for researchers. Microsoft Excel and Microsoft Word are used to convert tabular clinical data and produce an XML file in the TMA DES format. The BrowseTMA tool contains Extensible Stylesheet Language Transformation (XSLT) scripts that convert XML data into Hyper-Text Mark-up Language (HTML) web pages with hyperlinks automatically added to allow rapid navigation. RESULTS: Block lists, virtual slide images, legends, clinical details and exports have been placed on the ACSR web site for 14 blocks with 1623 cores of 2.0, 1.0 and 0.6 mm sizes. Our virtual microscope can be used to view and annotate these TMA images. Researchers can readily navigate from TMA block lists to TMA legends and to clinical details for a selected tissue core. Exports for 11 blocks with 3812 cores from three other institutions were processed with the BrowseTMA tool. Fifty common data elements (CDE) from the TMA DES were used and 42 more created for site-specific data. Researchers can download TMA clinical data in the TMA DES format. CONCLUSION: Virtual TMAs with clinical data can be viewed on the Internet by interested researchers using the BrowseTMA tool. We have organized our approach to producing, sorting, navigating and publishing TMA information to facilitate such review. We have converted Excel TMA data into TMA DES XML, and imported it and TMA DES XML from another institution into BrowseTMA to produce web pages that allow us to browse through the merged data. We proposed enhancements to the TMA DES as a result of this experience. We implemented improvements to the API TMA DES as a result of using exported data from several institutions. A document type definition was written for the API TMA DES (that optionally includes proposed enhancements). Independent validators can be used to check exports against the DTD (with or without the proposed enhancements). Linking tissue core images to readily navigable clinical data greatly improves the value of the TMA.

AIDS-Related Complex↗

PubMed2005

AIDS-related vasculopathy: evidence for oxidative and inflammatory pathways in murine and human AIDS.

Increased life expectancy of human immunodeficiency virus (HIV)-positive patients has led to evidence of complications apparently not directly related to immunodeficiency or opportunistic infection, including increased cardiovascular risk. We tested the hypothesis that vascular dysfunction occurs in the murine acquired immune deficiency syndrome (AIDS) model and evaluated potential mechanisms in murine AIDS tissues and relevant human HIV/AIDS vascular tissues. We also investigated endothelial activation and/or endothelial protein nitration and their association with time-dependent vascular dysfunction. At 1 and 5 wk of murine AIDS, statistically significant decreases in KCl contractility and time-dependent contractile deficits in response to phenylephrine were observed. The maximal response (E(max)) was reduced by approximately 40% at 10 wk, and EC(50) values were significantly changed: 102 +/- 7.3 ng for control vs. 190 +/- 37 and 130 +/- 22 ng at 5 and 10 wk, respectively (P < 0.05). Endothelium-dependent relaxation to ACh was decreased (EC(50) = 120 +/- 27 and 343 +/- 94 nM for control and at 10 wk, respectively), whereas the response to an exogenous nitric oxide donor, sodium nitroprusside, remained unchanged, suggesting a specific endothelial dysfunction. Histochemical investigations of the same vascular tissues as well as corresponding coronary endothelium showed an increase in protein 3-nitrotyrosine, intercellular adhesion molecule, and nitric oxide synthase isoforms 2 and 3. These findings were corroborated in concurrent experiments in a cohort of well-cataloged human cardiac microvascular tissues. We have demonstrated, for the first time, a specific functional vasculopathy with endothelial involvement in a murine model of AIDS that was also associated with and correlated to increased oxidative stress and specific endothelial activation. This finding was echoed in a relevant population of human HIV/AIDS patients. Research into sources and intracellular targets of oxidants in this disease could provide important mechanistic insights and may reveal new therapeutic opportunities for this increasingly important cardiovascular disease state.

Acquired Immunodeficiency Syndrome↗

PubMed2005

The tissue microarray data exchange specification: a document type definition to validate and enhance XML data.

BACKGROUND: The Association for Pathology Informatics (API) Extensible Mark-up Language (XML) TMA Data Exchange Specification (TMA DES) proposed in April 2003 provides a community-based, open source tool for sharing tissue microarray (TMA) data in a common format. Each tissue core within an array has separate data including digital images; therefore an organized, common approach to produce, navigate and publish such data facilitates viewing, sharing and merging TMA data from different laboratories. The AIDS and Cancer Specimen Resource (ACSR) is a HIV/AIDS tissue bank consortium sponsored by the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis (DCTD). The ACSR offers HIV-related malignancies and uninfected control tissues in microarrays (TMA) accompanied by de-identified clinical data to approved researchers. Exporting our TMA data into the proposed API specified format offers an opportunity to evaluate the API specification in an applied setting and to explore its usefulness. RESULTS: A document type definition (DTD) that governs the allowed common data elements (CDE) in TMA DES export XML files was written, tested and evolved and is in routine use by the ACSR. This DTD defines TMA DES CDEs which are implemented in an external file that can be supplemented by internal DTD extensions for locally defined TMA data elements (LDE). CONCLUSION: ACSR implementation of the TMA DES demonstrated the utility of the specification and allowed application of a DTD to validate the language of the API specified XML elements and to identify possible enhancements within our TMA data management application. Improvements to the specification have additionally been suggested by our experience in importing other institution's exported TMA data. Enhancements to TMA DES to remove ambiguous situations and clarify the data should be considered. Better specified identifiers and hierarchical relationships will make automatic use of the data possible. Our tool can be used to reorder data and add identifiers; upgrading data for changes in the specification can be automatically accomplished. Using a DTD (optionally reflecting our proposed enhancements) can provide stronger validation of exported TMA data.

AIDS-Related Complex↗

PubMed2004

Enteric gram-negative bacilli bloodstream infections: 17 years' experience in a neonatal intensive care unit.

OBJECTIVE: To assess the occurrence of enteric gram-negative bacilli (EGNB) bloodstream infections (BSI) in a neonatal intensive care setting during a 17-year period in which a consistent antibiotic treatment program was in place. To document infections, outbreaks, or epidemics, emergence of antibiotic resistance, clinical correlates, and outcomes of the most prevalent EGNB (Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae). METHODS: This study analyzed demographic, clinical, and bacteriologic information from 360 infants born 1986-2002 who developed 633 blood culture-proven BSI. A total of 121 EGNB were isolated (E coli, K pneumoniae, and E cloacae). Early-onset BSI were discovered within 48 hours from birth, and late-onset BSI were those that occurred thereafter. Suspected early-onset BSI were treated with ampicillin and gentamicin, suspected late-onset BSI with vancomycin and gentamicin. Antibiotics were changed on the basis of organism antimicrobial susceptibility. RESULTS: Early-onset BSI were noted in 52 of 21,336 (244/100,000) live births (1986-1991), 40 of 20,402 (196/100,000) live births (1992-1997), and 25 of 17,926 (139/100,000) live births (1998-2002). Of these cases, 39 were caused by E coli and 4 by K pneumoniae. Antibiograms for E coli isolated during the last 5 years of the study showed an increase in antibiotic resistance that coincided with obstetric group B streptococcus antepartum antibiotic prophylaxis. Group B streptococcus declined from 41 to 4 cases from the first to the last period. Late-onset BSI increased from 111 to 230 cases from the first to the second 6-year study period and declined modestly (171 cases) during the last. Fifteen percent (78 cases) of late-onset BSI were caused by EGNB, 5% by other gram-negative bacilli, 67% primarily by coagulase-negative staphylococcus, and 13% by fungus. Nonspecific clinical and hematologic signs of late-onset BSI were similar across EGNB species, but necrotizing enterocolitis was often associated with E coli, whereas pneumonia and prolonged thrombocytopenia characterized K pneumoniae infections. No outbreaks or epidemics were observed, and strains of EGNB with evidence of extended spectrum beta-lactamase production were never isolated. CONCLUSION: Antepartum antibiotic prophylaxis may have increased antibiotic resistance in E coli isolates from early-onset BSI but has dramatically decreased group B streptococcus infections. Late-onset BSI caused by EGNB increased, but without changes in antibiotic susceptibility. In spite of medical advances, E coli, K pneumoniae, and E cloacae remain responsible for significant morbidity and mortality, especially in very low birth weight infants.

Analysis of Variance↗

PubMed2004

HIV/AIDS-related cardiovascular disease.

Recent advances in antiretroviral therapies have enhanced survival of HIV/AIDS patients, but cardiovascular complications have emerged as important issues in this growing patient population. Although the antiviral drug therapies apparently yield cardiac and/or vascular toxicities themselves, several other factors associated with HIV pathogenesis have also been implicated. This brief review provides an overview of the significance and complexities of HIV/ AIDS-related cardiovascular complications and addresses some important mechanistic aspects that may contribute to this important clinical problem.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues.

OBJECTIVE: Cardiomyopathy and other vascular complications are now recognized as significant components of HIV/AIDS pathogenesis. Although the mechanisms involved in cardiomyopathy are poorly defined, a role for direct retroviral action and/or focal infiltration of activated immune cells have been postulated. Here we investigated mechanisms in retrovirus associated cardiomyopathy using a well-defined mouse model of acquired immunodeficiency. METHODS: Mice were dosed with LPBM5 retrovirus; cardiac performance was assessed by echocardiography followed by tissue collection at 5 and 10 weeks post-infection. RESULTS: Contractile deficits were observed at 5 and 10 weeks post-retrovirus infection and preceded the development of overt immunodeficiency. Selective and widespread cardiac infiltration of CD68+ cells, but not neutrophils, mast cells, or eosinophils was also observed at both 5 and 10 weeks. LPBM5 retrovirus was readily detectable in cardiac samples by RT-PCR. Time dependent increases in cardiac protein nitration (biomarker of reactive nitrogen species) were observed and were correlated to the extent of cardiac dysfunction whereas no changes in NOSII occurred at 5 and 10 weeks. We corroborated the mouse findings using cardiac tissues and clinical findings from human HIV/AIDS autopsies. CONCLUSIONS: These studies demonstrated that cardiac myocyte protein nitration in AIDS related cardiomyopathies, rather than focal immune cell lesions characterize retrovirus associated cardiomyopathies and differentiate them from non-retroviral cardiomyopathies.

Adult↗

PubMed2003

Using a modified standard microscope to generate virtual slides.

A standard microscope was reconfigured as a virtual slide generator by adding a Prior Scientific H101 robotic stage with H29 controller and 0.1 microm linear scales and a Hitachi HV-C20 3CCD camera. Media Cybernetics Image Pro Plus version 4 (IP4) software controlled stage movement in the X-, Y-, and Z-axis, whereas a Media Cybernetics Pro-Series Capture Kit captured images at 640 x 480 pixels. Stage calibration, scanning algorithms, storage requirements, and viewing modes were standardized. IP4 was used to montage the captured images into a large virtual slide image that was subsequently saved in TIF or JPEG format. Virtual slides were viewed at the workstation using the IP4 viewer as well as Adobe Photoshop and Kodak Imaging. MGI Zoom Server delivered the virtual slides to the Internet, and MicroBrightField's Neuroinformatica viewing software provided a browser-based virtual microscope interface together with labeling tools for annotating virtual slides. The images were served from a Windows 2000 platform with 2 GB RAM, 500 GB of disk storage, and a 1.0 GHz P4 processor. To conserve disk space on the image server, TIF files were converted to the FlashPix (FPX) file format using a compression ratio of 10:1. By using 4x, 10x, 20x, and 40x objectives, very large gigapixel images of tissue whole-mounts and tissue arrays with high quality and morphologic detail are now being generated for teaching, publication, research, and morphometric analysis. Technical details and a demonstration of our system can be found on the Web at http://virtualmicroscope.osu.edu.

Anatomy, Cross-Sectional↗

PubMed2003

Duration of empiric antibiotics for suspected early-onset sepsis in extremely low birth weight infants.

OBJECTIVES: To study multicenter antibiotic practices for suspected early-onset sepsis (EOS) with negative blood cultures (NegBCs) and to identify opportunities for reduction of antimicrobial exposure. DESIGN: Retrospective study. SETTING: Thirty academic hospitals (University HealthSystem Consortium) located in 24 states. METHODS: Data were from a survey of 790 extremely low birth weight (ELBW) infants. Total antibiotic exposures (antibiotic-days per patient) were calculated. RESULTS: On admission to the NICU, 94% of 790 ELBW infants had BCs performed and empiric antibiotics initiated. When PosBC and NegBC infants were compared, 47 patients with PosBCs were similar to 695 with NegBCs in birth weight, gestational age (GA), and mortality. Patients with suspected EOS but NegBCs given ampicillin/aminoglycosides were grouped by length of administration and GA. For GA of 26 weeks or younger, 170 infants given a short (< or = 3 days) and 157 given a long (> or = 7 days) course were similar regarding birth weight, mortality, antepartum history, and CRIB scores, but were different (P < .01) in number receiving a third antimicrobial (3% and 17%) and antibiotic-days (23 and 38). For GA of 27 weeks or older, 113 infants given a short and 77 given a long course differed (P < .01) in number receiving a third antimicrobial (2% and 23%) and antibiotic-days (19 and 30). CONCLUSIONS: Most suspected EOS infants with NegBCs are given antibiotics, but no antepartum historical risk factors or neonatal clinical signs explained prolonged administration. Discontinuing empiric antibiotics when BCs are negative in asymptomatic ELBW infants can reduce antimicrobial exposure without compromising clinical outcome.

Anti-Bacterial Agents↗

PubMed2002

Surveillance of ventilator-associated pneumonia in very-low-birth-weight infants.

BACKGROUND: Surveillance of ventilator-associated pneumonia (VAP) is an essential part of quality patient care. Very-low-birth-weight (VLBW) infants, many with tracheal microbial colonization and bronchopulmonary dysplasia (BPD), comprise a difficult group in whom to make a diagnosis of pneumonia with the Centers for Disease Control and Prevention (CDC) criteria for infants younger than 1 year. OBJECTIVE: Our objective was to retrospectively compare VAP surveillance diagnoses made by the hospital infection control practitioner (ICP) with those made by a panel of experts with the same clinical and laboratory evidence and supportive radiologic data. A secondary objective was to compare radiologic diagnosis of pneumonia made by the general hospital radiologists, by the panel of experts, and by a pediatric radiologist from another hospital. STUDY POPULATION: Thirty-seven VLBW infants identified as at risk for VAP by the ICP on the basis of a positive bacterial tracheal culture and the application of CDC criteria for the definition of pneumonia were studied. METHODS: Clinical and laboratory evidence and routine radiologic reports made by the general radiologist were reviewed independently by a panel of experts composed of 3 experienced neonatologists. Chest x-rays from the day before, day of, and day after the surveillance date were reviewed separately by the 3 neonatologists and also by a pediatric radiologist. RESULTS: After inter-reader reliability was found satisfactory (kappa's coefficient, 0.47-0.75; P <.05), the panel of neonatologists determined that the 37 VLBW infants represented 4 distinct clinical categories. Group 1 comprised 12 airway-colonized infants, aged 14 to 30 days, who on the surveillance date, albeit intubated, were asymptomatic, not treated with antibiotics, and survived. Group 2 comprised 11 airway-colonized infants, aged 7 to 42 days, who presented with equivocal clinical, laboratory, or radiologic signs of VAP and survived. Group 3 comprised 7 airway-colonized infants, aged 14 to 21 days, who were acutely ill (3 died) and had clinical and laboratory evidence of nosocomial bloodstream infection (BSI) but no radiologic signs of pneumonia. Group 4 comprised 7 infants, aged 14 to 28 days, who were acutely ill (4 died) and had clinical and laboratory evidence of infection and radiologic changes consistent with VAP. Radiologic Findings: General radiologists, neonatologists, and the pediatric radiologist agreed that none of the asymptomatic airway-colonized infants (Group 1) had VAP. General radiologists reported signs suggestive of pneumonia in 8 of 11 infants (Group 2), a finding not corroborated by the others. Everybody agreed on the absence of radiologic pneumonia in 6 of 7 patients with nosocomial BSI (Group 3) and on the presence of signs consistent with pneumonia in the remaining 7 infants (Group 4). CONCLUSION: Surveillance diagnosis of VAP in VLBW infants is difficult because current CDC definitions are not specific for this population. Isolated positive tracheal culture alone does not distinguish between bacterial colonization and respiratory infection. Clinical and laboratory signs of VAP, mostly nonspecific, can be found in other conditions such as bronchopulmonary dysplasia and nosocomial BSI. Routine radiologic reports suggestive of pneumonia in airway-colonized infants without definitive clinical and laboratory evidence of infection could be misleading. To improve accuracy, surveillance diagnosis of VAP in special populations such as VLBW infants should be reformulated; meanwhile, ICPs should seek consultation with experienced clinicians for interpretation of data.

Bronchopulmonary Dysplasia↗