Digital Commons Network^™

Bone Marrow Stromal Cells Use Tgf-Β To Suppress Allergic Responses In A Mouse Model Of Ragweed-Induced Asthma, K. Nemeth, A. Keane-Myers, J. M. Brown, D. D. Metcalfe, J. D. Gorham

Dartmouth Scholarship

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC- driven immunomodulation is mediated by the suppression of pro- inflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2- dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of …

Optimizing Vaccine Allocation At Different Points In Time During An Epidemic, Laura Matrajt, Ira M. Longini Jr.

UW Biostatistics Working Paper Series

For current pandemic influenza H1N1, vaccine production started in the early summer, and vaccination started in the fall. In most countries, by the time vaccination started, the second wave of H1N1 was already under way. With limited supplies of vaccine, it might be a good strategy to vaccinate the high-transmission groups earlier in the epidemic, but it might be a better use of resources to protect instead the high-risk groups later on. We develop a deterministic epidemic model with two age-groups (children and adults) and further subdivide each age group in low and high risk. We compare optimal vaccination strategies …

Changing Po2licy: The Elements For Improving Childhood Asthma Outcomes, Anne Rossier Markus, Meagan Lyon, Sara J. Rosenbaum

Geiger Gibson/RCHN Community Health Foundation Research Collaborative

Childhood asthma is a serious and chronic health issue that affects one in seven U.S. children and their families, compromising their health and quality of life and placing a heavy financial burden on families as well as an enormous strain on the health care system. Treating, managing, and ultimately preventing and reducing the burden of asthma represents a critical test of the ability of the U.S. health system – health insurers, clinical care providers, and public health agencies – to work together. Our investigation found that, as a country, we already know enough to act and improve life for the …

Acute Necrotizing Encephalopathy Of Childhood: A Fatal Complication Of Swine Flu, Muhammad Rehan Khan, Prem Kumar Maheshwari, Syed Asad Ali, Anwarul Haque

Department of Paediatrics and Child Health

Acute necrotizing encephalopathy of childhood (ANEC) is a rare condition characterized by the presence of multifocal symmetrical brain lesions involving mainly thalami, brainstem, cerebellum and white matter. ANEC is a serious and life threatening complication of simple viral infections. We present a case of a young child who developed this condition with classical clinical and radiological findings consistent with ANEC, secondary to swine flu (H1N1). He needed ventilatory support and had profound motor and intellectual deficit on discharge. We report this case with aim of raising awareness about this fatal complication of swine flu which has become a global health …

Modeling Super-Spreading Events For Sars, Thembinkosi P. Mkhatshwa

Theses, Dissertations and Capstones

One of the intriguing characteristics of the 2003 severe acute respiratory syndrome (SARS) epidemics was the occurrence of super spreading events (SSEs). Super-spreading events for a specific infectious disease occur when infected individuals infect more than the average number of secondary cases. The understanding of these SSEs is critical to under- standing the spread of SARS. In this thesis, we present a modification of the basic SIR (Susceptible - Infected - Removed) disease model, an SIPR (Susceptible - Regular Infected - Super-spreader - Removed) model, which captures the effect of the SSEs.

Cholera: An Overview Of A Disease, Ezriel Leifer

The Science Journal of the Lander College of Arts and Sciences

Although the disease, cholera, has been recognized since antiquity, the bacteria responsible for causing it was only discovered in the mid-19th century. Since 1817, cholera has spread on a global basis to cause seven pandemics. According to information reported to the World Health Organization in 1999, almost 8,500 people died and another 223,000 became sick with cholera worldwide. During the period between full outbreaks, the cholera organism, Vibrio cholerae, thrives in brackish waters, in harmless as well as disease-causing forms. Vibrio cholerae is just one of a variety of ocean-borne microbes that can sicken humans via seafood, drinking water, and …

Clostridium Difficile Associated Disease (Cdad), Rivka H. Borger

The Science Journal of the Lander College of Arts and Sciences

Clostridium difficile bacteria (C. difficile) are a spore-forming species of bacteria that lies dormant in the colon, in the presence of normal intestinal flora. Due to overuse of certain antibiotics, normal intestinal bacteria may be depleted, and combined with other possible risk factors, allow C. difficile bacterial spores to develop into active, infectious, and extremely resistant toxin-producing bacteria. The toxins cause severe damage and inflammation to the intestinal wall that can result in gastrointestinal discomfort and severe pseudomembranous enterocolitis that must be treated with a low-risk C. difficile targeting defense.

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IA^s/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.

Prevalence Of Hepatitis B And C Viral Infections In Pakistan: Findings Of A National Survey Appealing For Effective Prevention And Control Measures, H Qureshi, K M. Bile, Rashid Jooma, S E. Alam, H U R. Afridi

Section of Neurosurgery

A prevalence survey on hepatitis B and C infections was carried out to obtain national estimates and assess epidemiological dynamics and underlying risk factors. Overall prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) of 2.5% and 4.8%, respectively, reflected a combined infection rate of 7.6% in the general population, consistent with an ongoing high burden of chronic liver disease (CLD). There was significant association of these viral infections with a range of risk factors led by reuse of syringes. These findings validate currently implemented strategies by the national programme for the control of hepatitis viral infections, …

Recurrent Urinary Tract Infections In Females, Raheela Mohsin Rizvi, Khurram Mutahir Siddiqui

Department of Obstetrics & Gynaecology

Uncomplicated Urinary tract infections are common in adult women across the entire age spectrum, with mean annual incidence of 15% and 10% in those aged 15-39 and 40-79 years, respectively. Urinary tract infection (UTI), with its diverse clinical syndromes and affected host groups, remains one of the most common but widejly misunderstood and challenging infectious diseases encountered in clinical practice. Recurrent urinary tract infections (UTIs) present a significant problem for women and a challenge for the doctors who care for them. The diagnosis of uncomplicated UTI can be achieved best by a thorough assessment of patient symptoms with or without …

Practice Patterns For Antibiotic De-Escalation In Culture-Negative Healthcare-Associated Pneumonia, M. Schlueter, C. James, A. Dominguez, Laura V. Tsu, G. Seymann

Pharmacy Faculty Articles and Research

Background Published guidelines for the treatment of healthcare-associated pneumonia (HCAP) recommend initial broad-spectrum antibiotics with appropriate de-escalation based on culture results. Guideline recommendations are based on data from intubated patients, in whom cultures are easily obtained. The approach to antibiotic de-escalation for culture-negative patients has not been addressed. Consequently, there are no published reports that describe the current standard of practice. Patients and methods All patients admitted to a university hospital with a diagnosis of HCAP, as defined by use of a pneumonia orderset, were identified retrospectively over a 2-year period. Antibiotics prescribed on admission, during hospital stay, and on …

Rapid Emergence Of Co-Colonization With Community-Acquired And Hospital-Acquired Methicillin-Resistant Staphylococcus Aureus Strains In The Hospital Setting, Joanna R. Wares, Erika M.C. D'Agata, Glenn F. Webb

Department of Math & Statistics Faculty Publications

Background: Community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA), a novel strain of MRSA, has recently emerged and rapidly spread in the community. Invasion into the hospital setting with replacement of the hospital-acquired MRSA (HA-MRSA) has also been documented. Co-colonization with both CA-MRSA and HA-MRSA would have important clinical implications given differences in antimicrobial susceptibility profiles and the potential for exchange of genetic information.

Methods: A deterministic mathematical model was developed to characterize the transmission dynamics of HA-MRSA and CA-MRSA in the hospital setting and to quantify the emergence of co-colonization with both strains Results: The model analysis shows that the …

Using Modeling And Simulation To Evaluate Disease Control Measures, Tracy Atkins

Electronic Theses and Dissertations

This dissertation introduced several issues concerning the analysis of diseases by showing how modeling and simulation could be used to assist in creating health policy by estimating the effects of such policies. The first question posed was how would education, vaccination and a combination of these two programs effect the possible outbreak of meningitis on a college campus. After creating a model representative of the transmission dynamics of meningitis and establishing parameter values characteristic of the University of Central Florida main campus, the results of a deterministic model were presented in several forms. The result of this model was the …

Intravenous Artesunate For Severe Malaria, Karl M. Hess, Jeffery A. Goad, Paul M. Arguin

Pharmacy Faculty Articles and Research

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

DATA SYNTHESIS …

Synthesis, Antiviral And Contraceptive Activities Of Nucleoside-Sodium Cellulose Sulfate Acetate And Succinate Conjugates, Hitesh K. Agarwal, Anil Kumar, Gustavo F. Doncel, Keykavous Parang

Pharmacy Faculty Articles and Research

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2',3'-dideoxy-3'-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT-CSA and FLT-CSA) were found to be more potent than CS and other conjugates (e.g., AZT-succinate-CS, and FLT-succinate-CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type …

The Relationship Between Obesity And Skin And Soft Tissue Infections, Juliana Swiney

MPA/MPP/MPFM Capstone Projects

The Problem:

It is well known that our country is experiencing an obesity epidemic: 33.9% of all adults are obese (BMI>30) and 67% of adults are either overweight or obese (BMI>25). Obesity is a risk factor for several serious disease states such as, diabetes, stroke, hypertension, heart disease and some types of cancer. It also has a less well defined relationship with skin and soft tissue infections.

Although it is known that excessive weight increases the opportunity for harmful skin conditions, this relationship has not been as well studied. Some of the mechanisms that predispose obese people to …

Evaluating Children With Otitis Media For Bacteremia Or Urinary Tract Infection., Daniel Yawman, Patrick Mahar, Aaron Blumkin, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

Background. It is unclear if clinicians evaluate for concurrent bacteremia or UTI in young patients diagnosed with acute otitis media (AOM). Objectives. To describe how often, and under which circumstances, emergency providers investigate for bacteremia or UTI in 2-36 month olds with AOM. Methods. Cases of AOM were analyzed from the 2001-2004 National Hospital Ambulatory Medical Care Survey (NHAMCS)-Emergency Department dataset. Results. AOM was diagnosed in 17% of the 10,847 recorded visits of 2-36 month olds. Of these visits, laboratory testing included: CBC: 7%, Blood culture: 4%, urinalysis or urine culture: 5%, and any of these tests: 9%. Rates of …

The Effect Of Co-Colonization With Community-Acquired And Hospital-Acquired Methicillin-Resistant Staphylococcus Aureus Strains On Competitive Exclusion, Joanna R. Wares, Erika M.C. D'Agata, Glenn F. Webb

Department of Math & Statistics Faculty Publications

We investigate the in-hospital transmission dynamics of two methicillin-resistant Staphylococcus aureus(MRSA) strains: hospital-acquired methicillin resistant S. aureus (HA-MRSA) and community-acquired methicillin-resistant S. aureus (CA-MRSA). Under the assumption that patients can only be colonized with one strain of MRSA at a time, global results show that competitive exclusion occurs between HA-MRSA and CA-MRSA strains; the strain with the larger basic reproduction ratio will become endemic while the other is extinguished due to competition. Because new studies suggest that patients can be concurrently colonized with multiple strains of MRSA, we extend the model to allow patients to be co-colonized with HA-MRSA …

Studies Into Cytauxzoon And Helminth Infections Of Bobcats (Lynx Rufus) Of Northwest Arkansas, Emily Hickman, David Kreider, Chris Tucker, Jana Reynolds, Jeremy Powell, Tom Yazwinski

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

The purpose of this study was to determine the prevalence of Cytauxzoon felis and gastrointestinal helminth infections in bobcats (Lynx rufus) of Northwest Arkansas, an area known to have numerous cases of cytaux in domestic cats. Sixty bobcat carcasses were collected from trappers located in Mulberry and Decatur, Arkansas. Blood samples from the hearts were used to isolate Cytauxzoon DNA. Next, a polymerase chain reaction ( PCR) procedure coupled with gel-electrophoresis assay for the 18s region of extracted DNA were used to determine the presence of the protozoan in the bobcats at the time of harvest. Out of the 60 …

World Of Viruses: The Frozen Horror, Martin Powell, Tom Floyd, Angie Fox, Anisa Angeletti, Peter Angeletti, Judy Diamond, Kristin Watkins, Charles Wood

Books: College of Public Health

No abstract provided.

Ccl2 Responses To Mycobacterium Tuberculosis Are Associated With Disease Severity In Tuberculosis, Zahra Hasan, Jacqueline M. Cliff, Hazel M. Dockrell, Bushra Jamil, Muhammad Irfan, Mussarat Ashraf, Rabia Hussain

Section of Pulmonary & Critical Care

Background

Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.

Methodology

We investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, …

Reproductive Diseases Of Dairy Cattle, Christina Suzanne Tortosa

Dairy Science

The efficiency of today’s dairy has increased due to the growing number of cows per herd and the production of pounds of milk per cow. Increased milk production however has resulted in a reduction of conception rates causing a loss of income for the dairy producer since the dairy industry relies heavily on milk production, which is caused by good conception rates. Many reproductive disorders like dystocia, metritis, endometritis, and retained placenta affect conception rates, and can lead to metabolic diseases like rumen acidosis, milk fever, and displaced abomasums. Recurrent metabolic diseases can eventually lead to culling of the herd. …

Genetic Commonality Of Macrolide-Resistant Group A Beta Hemolytic Streptococcus Pharyngeal Strains, Angela Myers, Mary Anne Jackson, Rangaraj Selvarangan, Richard V. Goering, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Background: Group A beta hemolytic streptococcus (GABHS) pharyngitis is a common childhood illness. Penicillin remains the gold standard therapy, but macrolides are indicated for the penicillin allergic patient, and are often used for convenience.

Methods: We conducted a surveillance study of children with pharyngitis and positive streptococcal rapid antigen testing from 10/05 to 10/06 at 2 sites (A & B). Demographics, treatment, and resistance data was collected and compared to previous data from 2002. Erythromycin (EM) resistance was determined by disk diffusion and E-test on 500 isolates. Pulse field gel electrophoresis (PFGE) was performed to measure genetic relatedness of isolates. …

Pandemic Potential Of Reassortant Swine Influenza A Viruses, Christy Brockwell Staats

Theses and Dissertations (ETD)

Influenza A viruses are capable of causing disease in several species, including birds, humans and swine. Host specificity of the viruses is not absolute, and is influenced by a range of factors. Swine play a pivotal role in the interspecies transmission of influenza A viruses, as they are susceptible to infection with both human and avian strains and have been implicated as a “mixing vessel” for the reassortment of influenza A viruses from different species. The reassortment of influenza A viruses of human and avian origin led to human influenza pandemics in 1957 and 1968.

The dynamics of swine influenza …

Killing Of Treponema Denticola By Mouse Peritoneal Macrophages, P. Gaibani, C. Vocale, S. Ambretti, F. Cavrini, Jacques Izard, L. Miragliotta, M. T. Pellegrino, V. Sambri

Department of Food Science and Technology: Faculty Publications

Treponema denticola has been identified as an important cause of periodontal disease and hypothesized to be involved in extra-oral infections. The objective of this study was to investigate the role of T. denticola cell length and motility during mouse peritoneal macrophages in vitro uptake. Macrophages, incubated under aerobic and anaerobic conditions, produced a similar amount of TNF-α when stimulated with Escherichia coli LPS. The uptake of FlgE- and CfpA-deficient mutants of T. denticola was significantly increased compared with the wild-type strain, due to cell size or lack of motility. Opsonization with specific antibodies considerably improved the treponemes’ uptake. …

Tuberculous And Cryptococcal Meningitis In A Setting With High Tb And Low Hiv Prevalence, Afrasyab Khan, Bushra Jamil, Rahmat Ali, Sana Sultan

Section of Pulmonary & Critical Care

OBJECTIVE: To compare the differences in presentation and outcome of patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM).

STUDY DESIGN: Case series.

PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from December 1995 to December 2005.

METHODOLOGY: Patients with a confirmed diagnosis of TBM or CCM were included in this study. The signs and symptoms, laboratory findings and other variables of patients were entered and analyzed by Statistical Package for Social Sciences (SPSS) Software version 14.

RESULTS: We compared 16 patients of TBM with 11 of CCM. None of the patients with TBM were Human Immunodeficiency …

Community Acquired Pneumonia: Risk Factors Associated With Mortality In A Tertiary Care Hospitalized Patients, Muhammad Irfan, Syed Fayyaz Hussain, Khubaib Mapara, Shafia Memon, Mohammed Mogri, Muniza Bana, Amna Malik, Sara Khan, Nadia A Khan

Section of Pulmonary & Critical Care

OBJECTIVE: To evaluate risk factors associated with mortality in patients hospitalized with CommunityAcquired Pneumonia (CAP) from a developing country.

METHODS: An observational study was conducted on adult patients admitted with a diagnosis of CAP from January 2002 to August 2003 at Aga Khan University hospital, Karachi, Pakistan. Clinical records were reviewed for demographic characteristics, clinical and laboratory features, hospital course, and risk factors associated with mortality.

RESULTS: A total of 329 patients (187 males) were admitted with CAP. Two-third of patients had underlying co-morbid medical illnesses. Complications developed in 15.7% cases and the overall mortality rate was 11%. Risk factors …

Inhibition Of Yeast Hexokinase By The Antimalarial Drug Artemisinin: Probing Mechanism Of Action With A Model Enzyme, Jennifer S. Spence

Biological Sciences Theses & Dissertations

A leading infectious cause of death, malaria threatens approximately half of the world's population, and drug-resistant strains of Plasmodium falciparum have created immense difficulty in chemotherapy of the disease. The artemisinin (ART) class of antimalarials may represent a powerful solution. In addition to their safety, effectiveness, and moderate cost, they are the only drugs in use for which there has been no widespread evidence of clinical resistance. The exact parasiticidal mechanism of ART is highly contested, but evidence suggests that protein alkylation may play a role in cytotoxicity. in vitro essays were performed using yeast hexokinase (HK) to demonstrate a …

Directing Diarrhoeal Disease Research Towards Disease-Burden Reduction, Margaret Kosek, Claudio F. Lanata, Robert E. Black, Damian G. Walker, John D. Snyder, Mohammed Abdus Salam, Dilip Mahalanabis, Olivier Fontaine, Zulfiqar Ahmed Bhutta, Shinjini Bhatnagar, Igor Rudan

Woman and Child Health

Despite gains in controlling mortality relating to diarrhoeal disease, the burden of disease remains unacceptably high. To refocus health research to target disease-burden reduction as the goal of research in child health, the Child Health and Nutrition Research Initiative developed a systematic strategy to rank health research options. This priority-setting exercise included listing of 46 competitive research options in diarrhoeal disease and their critical and quantitative appraisal by 10 experts based on five criteria for research that reflect the ability of the research to be translated into interventions and achieved disease-burden reduction. These criteria included the answerability of the research …

A Comparison Of Fluoroquinolones Versus Other Antibiotics For Treating Enteric Fever: Meta-Analysis, Durrane Thaver, Anita K. M. Zaidi, Julia Critchley, Asma Azmatullah, Syed Ali Madni, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Objectives: To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever).
Design: Meta-analysis of randomised controlled trials. Data sources: Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline (1966-2007), Embase (1974-2007), LILACS (1982-2007), selected conferences, reference lists, and ongoing trial register (November 2007).
Review methods: Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on …