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Find video protocols related to scientific articles indexed in Pubmed.
Toll-like receptor 4 stimulation before or after Streptococcus pneumoniae induced sepsis improves survival and is dependent on T-cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Endotoxin tolerance improves outcomes from gram negative sepsis but the underlying mechanism is not known. We determined if endotoxin tolerance before or after pneumococcal sepsis improved survival and the role of lymphocytes in this protection.
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Macrophage migration inhibitory factor (MIF) is a critical mediator of the innate immune response to Mycobacterium tuberculosis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-23-2013
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Macrophage migration inhibitory factor (MIF), an innate cytokine encoded in a functionally polymorphic genetic locus, contributes to detrimental inflammation but may be crucial for controlling infection. We explored the role of variant MIF alleles in tuberculosis. In a Ugandan cohort, genetic low expressers of MIF were 2.4-times more frequently identified among patients with Mycobacterium tuberculosis (TB) bacteremia than those without. We also found mycobacteria-stimulated transcription of MIF and serum MIF levels to be correlated with MIF genotype in human macrophages and in a separate cohort of US TB patients, respectively. To determine mechanisms for MIFs protective role, we studied both aerosolized and i.v. models of mycobacterial infection and observed MIF-deficient mice to succumb more quickly with higher organism burden, increased lung pathology, and decreased innate cytokine production (TNF-?, IL-12, IL-10). MIF-deficient animals showed increased pulmonary neutrophil accumulation but preserved adaptive immune response. MIF-deficient macrophages demonstrated decreased cytokine and reactive oxygen production and impaired mycobacterial killing. Transcriptional investigation of MIF-deficient macrophages revealed reduced expression of the pattern recognition receptor dectin-1; restoration of dectin-1 expression recovered innate cytokine production and mycobacterial killing. Our data place MIF in a crucial upstream position in the innate immune response to mycobacteria and suggest that commonly occurring low expression MIF alleles confer an increased risk of TB disease in some populations.
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Mycobacterium tuberculosis bacteremia in a cohort of HIV-infected patients hospitalized with severe sepsis in Uganda-high frequency, low clinical sand derivation of a clinical prediction score.
PLoS ONE
PUBLISHED: 01-01-2013
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When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.
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Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis.
Crit. Care Med.
PUBLISHED: 06-14-2011
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Dysglycemia during sepsis is associated with poor outcomes in resource-rich settings. In resource-limited settings, hypoglycemia is often diagnosed clinically without the benefit of laboratory support. We studied the utility of point-of-care glucose monitoring to predict mortality in severely septic patients in Uganda.
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The Infectious Diseases Institute at Makerere University, Kampala, Uganda.
Infect. Dis. Clin. North Am.
PUBLISHED: 06-02-2011
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The Infectious Diseases Institute (IDI) at Makerere University, Kampala, Uganda, was created in 2001. This article outlines its origins, principles, clinical programs, training activities, research programs, organizational structure, leadership, and contributions to Makerere University and its College of Health Sciences.
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Molecular dissection of an outbreak of carbapenem-resistant enterobacteriaceae reveals Intergenus KPC carbapenemase transmission through a promiscuous plasmid.
MBio
PUBLISHED: 01-01-2011
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Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as major causes of health care-associated infections worldwide. This diverse collection of organisms with various resistance mechanisms is associated with increased lengths of hospitalization, costs of care, morbidity, and mortality. The global spread of CRE has largely been attributed to dissemination of a dominant strain of Klebsiella pneumoniae producing a serine ?-lactamase, termed K. pneumoniae carbapenemase (KPC). Here we report an outbreak of KPC-producing CRE infections in which the degree of horizontal transmission between strains and species of a promiscuous plasmid is unprecedented. Sixteen isolates, comprising 11 unique strains, 6 species, and 4 genera of bacteria, were obtained from 14 patients over the first 8 months of the outbreak. Of the 11 unique strains, 9 harbored the same highly promiscuous plasmid carrying the KPC gene bla(KPC). The remaining strains harbored distinct bla(KPC) plasmids, one of which was carried in a strain of Klebsiella oxytoca coisolated from the index patient and the other generated from transposition of the bla(KPC) element Tn4401. All isolates could be genetically traced to the index patient. Molecular epidemiological investigation of the outbreak was aided by the adaptation of nested arbitrary PCR (ARB-PCR) for rapid plasmid identification. This detailed molecular genetic analysis, combined with traditional epidemiological investigation, provides insights into the highly fluid dynamics of drug resistance transmission during the outbreak. IMPORTANCE The ease of horizontal transmission of carbapenemase resistance plasmids across strains, species, and genera of bacteria observed in this study has several important public health and epidemiological implications. First, it has the potential to promote dissemination of carbapenem resistance to new populations of Enterobacteriaceae, including organisms of low virulence, leading to the establishment of reservoirs of carbapenem resistance genes in patients and/or the environment and of high virulence, raising the specter of untreatable community-associated infections. Second, recognition of plasmid-mediated outbreaks, such as those described here, is problematic because analysis of resistance plasmids from clinical isolates is laborious and technically challenging. Adaptation of nested arbitrary PCR (ARB-PCR) to investigate the plasmid outbreak facilitated our investigation, and the method may be broadly applicable to other outbreaks due to other conserved mobile genetic elements. Whether infection control measures that focus on preventing transmission of drug-resistant clones are effective in controlling dissemination of these elements is unknown.
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Principles of antimicrobial therapy.
Handb Clin Neurol
PUBLISHED: 01-19-2010
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We have discussed important factors involved in choosing appropriate antimicrobial regimens for the treatment of bacterial meningitis and brain abscess to illustrate common themes relevant to the treatment of these diseases. We have limited this review to these conditions for two main reasons: (1) the principles involved in optimal antimicrobial therapy for these diseases likely apply to others CNS infections, such as viral and fungal diseases; and (2) little pharmacological information is currently available for other types of CNS infections. Many of the studies addressing the relevant pharmacological and microbiological aspects of antimicrobial therapy for CNS infections have been performed in experimental animal models and, as a result, the information derived from these studies may be different when examined in appropriate human studies. Our current understanding of appropriate antimicrobial therapy for CNS infections may be summarized as follows: 1. Choose bactericidal antimicrobials that effectively cross the BBB to achieve CSF concentrations well above the MBC (? 10-fold) for the suspected bacterial pathogen(s). 2. Take into consideration the relevant PD parameters the bactericidal activity of the antimicrobials used to treat bacterial meningitis, such as t > MBC or AUC/MBC. 3. Tailor the antimicrobial regimen based on microbiological information, once available. However, with respect to brain abscess therapy, keep in mind that anaerobes are commonly involved, but difficult to culture, and consider including antianaerobic therapy even if the bacterial cultures do not grow anaerobes. 4. Treat bacterial meningitis caused by nonmeningococcal pathogens for 7-10 days, but monitor clinical progress to determine whether the patient should continue on a more prolonged antimicrobial course. Meningococcal meningitis may be treated with 3-4 days of effective antimicrobial therapy, again with the caveat that the patients clinical course should dictate duration of therapy. 5. Treat brain abscess, preferably after aspiration/drainage, for at least 6 weeks with intravenous antimicrobials for brain abscess on the clinical response (e.g., improved symptoms, lack of new neurological findings) and radiographic changes (e.g., reduction in cavity size).
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Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda.
Hum Resour Health
PUBLISHED: 08-23-2009
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To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted.
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Antimicrobial agents for complicated skin and skin-structure infections: justification of noninferiority margins in the absence of placebo-controlled trials.
Clin. Infect. Dis.
PUBLISHED: 06-27-2009
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The United States Food and Drug Administration requires clinical trial noninferiority margins to preserve a fraction (eg, 50%) of the established comparator drugs efficacy versus placebo. Lack of placebo-controlled trials for many infections complicates noninferiority margin justification for and, hence, regulatory review of new antimicrobial agents. Noninferiority margin clarification is critical to enable new antimicrobial development. In the absence of placebo-controlled trials, we sought to define the magnitude of efficacy of antimicrobial agents and resulting noninferiority margins for studies of complicated skin and skin-structure infection (SSSI).
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Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population.
PLoS ONE
PUBLISHED: 05-05-2009
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Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality.
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Treatment of severe sepsis with artemether-lumefantrine is associated with decreased mortality in Ugandan patients without malaria.
Am. J. Trop. Med. Hyg.
PUBLISHED: 05-02-2009
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We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank chi(2) = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores
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The expansion of the microbiological spectrum of brain abscesses with use of multiple 16S ribosomal DNA sequencing.
Clin. Infect. Dis.
PUBLISHED: 04-02-2009
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Background. Brain abscess is commonly treated using empirically prescribed antibiotics. Thus, a comprehensive study of bacterial organisms associated with brain abscess is essential to define the best empirical treatment for this life-threatening condition. Methods. We prospectively compared cultures to single and multiple sequenced 16S ribosomal DNA polymerase chain reaction amplifications (by cloning and/or pyrosequencing) of cerebral abscesses in 20 patients from 2 hospitals in Marseilles, France, during the period January 2005 through December 2007. Results. The obtained cultures identified significantly fewer types of bacteria (22 strains) than did molecular testing (72 strains; P = .017, by analysis of variance test). We found that a patient could exhibit as many as 16 different bacterial species in a single abscess. The obtained cultures identified 14 different species already known to cause cerebral abscess. Single sequencing performed poorly, whereas multiple sequencing identified 49 species, of which 27 had not been previously reported in brain abscess investigations and 15 were completely unknown. Interestingly, we observed 2 patients who harbored Mycoplasma hominis (an emerging pathogen in this situation) and 3 patients who harbored Mycoplasma faucium, which, to our knowledge, has never been reported in literature. Conclusions. Molecular techniques dramatically increased the number of identified agents in cerebral abscesses. Mycoplasma species are common and should be detected in this situation. These findings led us to question the accuracy of the current empirical treatment of brain abscess.
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Disseminated strongyloidiasis complicating glioblastoma therapy: a case report.
J. Neurooncol.
PUBLISHED: 03-19-2009
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Strongyloides stercoralis is an intestinal parasite that can cause fatal opportunistic infections in immunocompromised patients. Here we report an immunocompromised patient with glioblastoma who developed disseminated strongyloidiasis 6 weeks after completion of standard radiotherapy and concurrent temozolomide chemotherapy. She was effectively treated with albendazole and ivermectin. Strongyloidiasis should be considered in patients being treated for glioma who have lived or traveled to high risk areas and developed gram negative sepsis, along with gastrointestinal or respiratory symptoms, skin rash or SIADH.
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Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America.
Clin. Infect. Dis.
PUBLISHED: 01-03-2009
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The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
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Enrichment of HIV-1 subtype AD recombinants in a Ugandan cohort of severely septic patients.
PLoS ONE
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Several population-wide HIV-1 subtype distribution studies in Uganda have evaluated relatively healthy clinic patients. Given the differences in HIV-1 disease progression based on subtype, we examined HIV-1 subtype distribution and disease outcomes among hospitalized patients with severe sepsis.
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The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study*.
Crit. Care Med.
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In sub-Saharan Africa, sepsis is an important cause of mortality. Optimal sepsis management including fluid resuscitation, early antibiotic administration, and patient monitoring is limited by lack of supplies and skilled health workers.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.