Myron S. Cohen

Bio: Myron S. Cohen is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Population & Acquired immunodeficiency syndrome (AIDS). The author has an hindex of 103, co-authored 549 publications receiving 46021 citations. Previous affiliations of Myron S. Cohen include University of Massachusetts Medical School & Scripps Health.

Differential extracellular and intracellular concentrations of zidovudine and lamivudine in semen and plasma of HIV-1-infected men.

Abstract: Unprotected sexual intercourse is the predominant risk factor for acquiring HIV, with most transmission occur- ring from infected men to male and female partners.1 The efficiency of HIV transmission depends on a variety of factors, including the type of sex act, the viral burden of the infected partner, and the susceptibility of the uninfected partner to HIV infection.2–7 Although behavioral interventions, such as condom use, have been successful in reducing transmission,8–10 approximately 4 million adults and children are infected globally on a yearly basis.1 New and novel prevention methods are urgently needed to slow the spread of the epidemic. One potential mechanism to slow HIV transmission is the use of antiretroviral drugs (ARVs) to reduce HIV RNA concentrations in infectious secretions. ARV therapy has been shown reliably to decrease HIV RNA concentrations in the genital tract (GT),11–14 and lower semen HIV RNA concentrations are expected to decrease the efficiency of sexual transmission. Chakraborty and colleagues4 predict that a semen HIV RNA concentration of 100,000 copies/mL would result in transmission in 1 per 100 episodes of heterosexual intercourse, whereas a seminal viral load of 1000 copies/mL would decrease the probability of transmission to 3 per 10,000 acts. The relation between HIV RNA concentrations in blood plasma (BP) and semen is imperfect,15–18 and careful examination of viral sequences demonstrates that BP and GT can be viewed as separate viral compartments.19–21 Persistent GT HIV RNA shedding in subjects receiving ARVs has been reported,22 and long-lived resistant variants in the GT represent a particular problem for rebound viremia23 and transmitted resistance.19 It seems likely that poor penetration or altered metabolism of ARVs in the GT contribute to this problem.24 Nucleoside reverse transcriptase inhibitors (NRTIs) such as lamivudine (3TC) and zidovudine (ZDV) form the backbone of a typical ARV regimen, and this combination is currently recommended as an alternative option for initial treatment of HIV infection by the US Department of Health and Human Services.25 Random BP and seminal plasma (SP) concentrations of these drugs have been measured previously,14,26,27 and investigators have noted ZDV and 3TC concentrations to be 2 to 9 times higher in SP than in BP. As with all NRTIs, however, the active moiety is the triphosphate (TP) metabolite formed by intracellular enzymatic processes.28 Higher intracellular 3TC-TP and ZDV-TP concentrations in peripheral blood mononuclear cells (PBMCs) have been correlated with a faster decline in HIV RNA concentrations and an increase in CD4 T-cell counts.29 TP concentrations have not been previously characterized in GT mononuclear cells but are likely critical for NRTI efficacy locally. Here, we report on a comprehensive evaluation of extracellular and intracellular ZDV and 3TC concentrations in the male GT over a 12-hour dosing interval under steady-state conditions.

HIV Treatment As Prevention: How Scientific Discovery Occurred And Translated Rapidly Into Policy For The Global Response

Abstract: In 2011 interim results of HIV Prevention Trials Network study 052, a National Institutes of Health study designed to test the effectiveness of antiretroviral treatment against the spread of HIV, were reported. These results showed that in a stable relationship in which one member of the couple was infected with HIV, treatment of the infected partner with antiretroviral drugs, combined with couples counseling and condom use, resulted in a 96 percent reduction in sexual transmission of HIV-1. This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention. Independent advisory committees of the President’s Emergency Plan for AIDS Relief (PEPFAR) and the World Health Organization (WHO) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention. This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospective new trials to test how best to maximize the benefits of early treatment for pr...

A Neisseria gonorrhoeae immunoglobulin A1 protease mutant is infectious in the human challenge model of urethral infection.

Abstract: Many mucosal pathogens, including Neisseria gonorrhoeae, produce proteases that cleave immunoglobulin A (IgA), the predominant immunoglobulin class produced at mucosal surfaces. While considerable circumstantial evidence suggests that IgA1 protease contributes to gonococcal virulence, there is no direct evidence that N. gonorrhoeae requires IgA1 protease activity to infect a human host. We constructed a N. gonorrhoeae iga mutant without introducing new antibiotic resistance markers into the final mutant strain and used human experimental infection to test the ability of the mutant to colonize the male urethra and to cause gonococcal urethritis. Four of the five male volunteers inoculated with the Iga− mutant became infected. In every respect—clinical signs and symptoms, incubation period between inoculation and infection, and the proportion of volunteers infected—the outcome of human experimental infection with FA1090iga was indistinguishable from that previously reported for a variant of parent strain FA1090 matching the mutant in expression of Opa proteins, lipooligosaccharide, and pilin. These results indicate that N. gonorrhoeae does not require IgA1 protease production to cause experimental urethritis in males.

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Abstract: Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

Role of free radicals and catalytic metal ions in human disease: an overview.

Abstract: Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

Abstract: 1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Sexually transmitted diseases treatment guidelines.

Abstract: The MMWR series of publications is published by the Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30333.