Kaposi's sarcoma with a non-Hodgkin's lymphoma. Its association in a male homosexual with human T-cell lymphotropic virus type III infection

Combined tumor syndromes, specifically reticuloendothelial malignancies and Kaposi’s sarcoma, have long been recognized. With the recognition of the acquired immunodeficiency syndrome (AIDS), several patients with concurrent non-Hodgkin’s lymphoma and Kaposi’s sarcoma have been reported at high risk for developing AIDS. The present Centers for Disease Control definition of AIDS excludes these patients on the assumption that one tumor is affecting the cellular immunity, allowing for the development of the second malignancy. In evaluating such a patient who had serologic evidence of human T-cell lymphotropic virus type III infection, the probable cause of AIDS, we have reviewed reports of patients with similar concurrent malignancies before and since the onset of the AIDS epidemic. We conclude that patients in high-risk groups for AIDS who develop similar combined tumor syndromes should be classified as having AIDS

Studies in homosexual patients with and without lymphadenopathy - Relationships to the acquired immune deficiency syndrome

We studied the immunologic function of 19 sexually active homosexual men, ten of whom had persistent lymphadenopathy. Analysis of mononuclear cell populations distinguished homosexuals from heterosexual controls since, as a group, homosexuals had increased percentages of natural killer cells (Leu 7+), decreased helper-inducer T lymphocytes (OKT-4+), increased suppressor/cytotoxic (OKT-8+) T lymphocytes, low OKT-4:OKT-8 ratios, and depressed mitogenic responses. Homosexuals without lymphadenopathy were distinguishable from controls by increased percentages of la+ cells, decreased OKT-4+ cells, and decreased OKT-4:OKT-8 ratios. Four had positive findings simultaneously for hepatitis B surface antigen (HBsAg) and surface antibody, and five had positive findings for HBsAg alone. Homosexuals with lymphadenopathy were distinguishable from controls by increased percentages of Leu 7+ cells, increased total lymphocyte numbers per cubic millimeter, decreased percentages of both OKT-4+ and OKT-8+ cells, abnormal OKT-4:OKT-8 ratios, and depressed mitogenic responses. Only histories of larger numbers of sexually acquired diseases, higher numbers of OKT-8+ cells per cubic millimeter, and lower mitogenic responses in homosexuals with lymphadenopathy distinguished this group from homosexuals without lymphadenopathy. Furthermore, none of the nine patients tested in this group was HBsAg positive. We conclude that homosexuals without lymphadenopathy are distinguishable from those with lymphadenopathy by both immunologic and serologic abnormalities

Analytical protocols for separation and electron microscopy of nanoparticles interacting with bacterial cells

An important step toward understanding interactions between nanoparticles (NPs) and bacteria is the ability to directly observe NPs interacting with bacterial cells. NPbacteria mixtures typical in nanomedicine, however, are not yet amendable for direct imaging in solution. Instead, evidence of NPcell interactions must be preserved in derivative (usually dried) samples to be subsequently revealed in high-resolution images, e.g., via scanning electron microscopy (SEM). Here, this concept is realized for a mixed suspension of model NPs and Staphylococcus aureus bacteria. First, protocols for analyzing the relative colloidal stabilities of NPs and bacteria are developed and validated based on systematic centrifugation and comparison of colony forming unit (CFU) counting and optical density (OD) measurements. Rate-dependence of centrifugation efficiency for each component suggests differential sedimentation at a specific predicted rate as an effective method for removing free NPs after co-incubation; the remaining fraction comprises bacteria with any associated NPs and can be examined, e.g., by SEM, for evidence of NPbacteria interactions. These analytical protocols, validated by systematic control experiments and high-resolution SEM imaging, should be generally applicable for investigating NPbacteria interactions.financial support from the following sources: grant SFRH/BPD/47693/2008 from the Portuguese Foundation for Science and Technology (FCT); FCT Strategic Project PEst-OE/EQB/LA0023/2013; project “BioHealth Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027, cofunded by the Programa Operacional Regional do Norte (ON.2−O Novo Norte), QREN, FEDER; project “Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB”, ref. FCOMP-01-0124-FEDER- 027462

Daptomycin antimicrobial activity tested against methicillin-resistant staphylococci and vancomycin-resistant enterococci isolated in European medical centers (2005)

BACKGROUND: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005. METHODS: A total of 4,640 strains from 23 medical centers located in 10 European countries, Turkey and Israel (SENTRY Program platform) were tested for susceptibility by reference broth microdilution methods according to Clinical and Laboratory Standards Institute guidelines and interpretative criteria. Mueller-Hinton broth was supplemented to 50 mg/L Ca(++ )for testing daptomycin. Results for oxacillin (methicillin)-resistant staphylococci and vancomycin-resistant enterococci were analyzed separately. RESULTS: Oxacillin resistance rates among Staphylococcus aureus varied from 2.1% in Sweden to 42.5% in the United Kingdom (UK) and 54.7% in Ireland (29.1% overall), while vancomycin resistance rates varied from 0.0% in France, Sweden and Switzerland to 66.7% in the UK and 71.4% in Ireland among Enterococcus faecium (17.9% overall). All S. aureus strains were inhibited at daptomycin MIC of 1 mg/L (MIC(50/90), 0.25/0.5 mg/L; 100.0% susceptible) and only one coagulase-negative staphylococci strain (0.1%) showed an elevated (>1 mg/L) daptomycin MIC value (4 mg/L). Among E. faecalis (MIC(50/90), 0.5/1 mg/L; 100% susceptible) the highest daptomycin MIC value was 2 mg/L; while among E. faecium (MIC(50/90), 2/4 mg/L; 100% susceptible) the highest MIC result was 4 mg/L. CONCLUSION: Daptomycin showed excellent in vitro activity against staphylococci and enterococci collected in European medical centers in 2005 and resistance to oxacillin, vancomycin or quinupristin/dalfopristin did not compromise its activity overall against these pathogens. Based on these results and those of previous publications, daptomycin appears to be an excellent therapeutic option for serious infections caused by oxacillin-resistant staphylococci and vancomycin-resistant enterococci in Europe

Drug Resistance in Eukaryotic Microorganisms

Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies