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.

Classical Sexually Transmitted Diseases Drive the Spread of HIV-1: Back to the Future

Abstract: The transmission of human immunodeficiency virus type 1 (HIV-1) depends on the infectiousness of the index case (ie, vector) and the susceptibility of the host [1]. The probability of the transmission event has been extensively studied [1–3], and the risk is often described as about 1 in 1000 coital events [4]. However, large numbers of exposures like these are often derived from studies of stable, heterosexual, discordant couples [4, 5]. By definition, the HIV-1–negative partners in these couples can be defined as “exposed and uninfected” at the time of enrollment. The transmission of HIV-1 is almost certainly often more efficient than reflected in studies of couples and is likely enhanced by amplifying factors [6]. Perhaps no other HIV transmission cofactor has attracted as much attention as sexually transmitted diseases (STDs). More than 20 years ago, Wasserheit and colleagues described the transparent and omnipresent relationship between classical STDs and HIV-1, coining this unfortunate marriage of pathogens “epidemiologic synergy” [7].We subsequently showed that infection with Neisseria gonorrhoeae greatly increased shedding of HIV-1from the male genital tract in seminal plasma, offering a biological view of such synergy [8]. In recent years, however, interest in the relationship between STDs and HIV-1 has waned, primarily because it has proven nearly impossible to reduce the spread of HIV-1 through directed or empirical treatment of STDs [9]. In this issue of The Journal of Infectious Diseases, Mlisana et al [10] contribute to this consideration. Because of the limited laboratory infrastructure in lowand middle-income countries, treatment of STDs in women often depends on the recognition of signs and symptoms of vaginal discharge, leading to empirical treatment with antibiotics [11, 12]. Syndromic management is important but often suboptimal since a substantial number of people using this method are overor undertreated [11, 12]. Mlisana and colleagues [10] have further expanded our concerns about syndromic management. Two-hundred forty-two women at risk for HIV-1 infection were enrolled in a prospective cohort. Four things were measured: the presence or absence of a vaginal discharge, detection of ≥1 STD pathogens, vaginal cytokine concentrations, and HIV-1 acquisition. The results offered a stark reality for HIV-1 prevention and demonstrate yet again that STDs represent a “hidden epidemic,” the title of a compelling Institute of Medicine report published more than a decade ago [13]. Only 12.3% of women infected with a pathogen that might cause a vaginal discharge had signs or symptoms of infection. Women with STDs were >3-fold more likely to acquire HIV-1 than those who harbored no pathogens. Women with gonococcal infections, among the most inflammatory of the classical STD agents [14], had had an eye-opening 7fold increased risk of HIV-1 acquisition, bringing us full circle to earlier reports [8]. Surprisingly, inflammatory cytokines were not significantly different in women with symptomatic STDs, compared with asymptomatic infections, although they were greater than in women with no STDs or with bacterial vaginosis. Passmore et al [15] have reported that some unique inflammatory cytokine profiles predict risk for HIV acquisition. How can we fit these observations into sensible HIV-1 prevention strategies? Padian et al [9] have provided an exhaustive summary of interventions designed to prevent HIV-1 transmission, emphasizing the general lack of prevention benefit with treatment of classical STDs. The failure of this approach, in my opinion, is not because STDs are not critically important. Rather, we are simply unable to treat the right infections with the right drugs at the right times, and so the results of the interventions prove disappointing. Sadly, except for hepatitis B virus vaccine and HPV vaccine, STD vaccines are not available. Received 10 February 2012; accepted 13 February 2012; electronically published 19 April 2012. Correspondence: Myron S. Cohen, MD, 130 Mason Farm Rd, CB 7030, University of North Carolina, Chapel Hill, NC 27599-7030 (mscohen@med.unc.edu). The Journal of Infectious Diseases 2012;206:1–2 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/infdis/jis303

Differences in HIV-Specific T Cell Responses between HIV-Exposed and -Unexposed HIV-Seronegative Individuals†

Abstract: HIV-1-specific T lymphocyte responses in individuals exposed to HIV-1 but who remain persistently seronegative (HESNs) have been reported in some but not all previous studies. This study was designed to resolve unequivocally the question of whether HESNs make HIV-1-specific T cell responses. We performed a blind investigation to measure HIV-1-specific T cell responses in both HIV-1-serodiscordant couples and HIV-1-unexposed seronegative controls (HUSNs). We found low-frequency HIV-1-specific T cells in both HESNs and HUSNs but show that the response rates were higher over time in the former (P = 0.01). Furthermore, the magnitudes of the HIV-1-specific T cell responses were significantly higher among responding HESNs than among HUSNs over time (P = 0.002). In both groups, responses were mediated by CD4 T cells. The responses were mapped to single peptides, which often corresponded to epitopes restricted by multiple HLA-DR types that have previously been detected in HIV-1-infected patients. HIV-1-specific T cell responses in HUSNs and some HESNs likely represent cross-reactivity to self or foreign non-HIV-1 antigens. The significantly greater T cell responses in HESNs, including in two who were homozygous for CCR5Δ32, demonstrates that HIV-1-specific T cell responses can be induced or augmented by exposure to HIV-1 without infection.

Phagocytes, O2 Reduction, and Hydroxyl Radical

Abstract: The formation of O2 reduction products by human neutrophils is critical to their elimination of potential pathogens. Hydroxyl radical is a potent oxidizing agent that may be formed by neutrophils through the iron-catalyzed reaction of superoxide and its dismutation product, hydrogen peroxide. Although indirect evidence has implicated hydroxyl radical in a variety of neutrophil-mediated processes, recent studies have not demonstrated hydroxyl radical formation by neutrophils unless an exogenous iron source and chelator were available, and even then neutrophils appear to limit formation of hydroxyl radical. By consuming hydrogen peroxide, the release of myeloperoxidase limits the magnitude of hydroxyl radical production. Lactoferrin released during neutrophil stimulation binds iron in a form incapable of catalyzing hydroxyl radical generation, thereby limiting both the magnitude and the duration of hydroxyl radical formation. Hydroxyl radical resulting from neutrophil superoxide production is likely to occur either in vitro or in vivo only when the target cell (or microenvironment) provides iron in an oxidation state and form capable of catalyzing the formation of hydroxyl radical and when neutrophil prevention systems are overwhelmed.

Azithromycin Treatment Failure Among Primary and Secondary Syphilis Patients in Shanghai

Abstract: Background: Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy. Methods: Patients who did not respond to azithromycin therapy were referred to Shanghai Skin Disease and sexually transmitted disease hospital. Treatment failure was defined as follows: (1) persistent ulcers or cutaneous or mucosal lesions 1 month after therapy; or (2) detection of spirochetes in dark-field microscopy examination of a lesion at least 1 week after treatment; or (3) failure of rapid plasma reagin titers to decrease 4-fold at 3 months after treatment. Results: A total of 132 patients with primary and secondary syphilis who failed azithromycin therapy were referred to our hospital between January 2001 and October 2008. Of 132 patients, 42 (31.8%) had primary syphilis and 90 (68.2%) had secondary syphilis. Twenty-six patients with primary syphilis developed multiple lesions or secondary syphilis, or persistent ulcers despite using azithromycin. The skin or mucosal lesions did not resolve in 37 patients with secondary syphilis after azithromycin treatment. Ten patients had a positive dark-field examination for Treponema pallidum (T. pallidum) after treatment. The serum rapid plasma reagin titers studied in all cases had failed to decrease 4-fold at 3 months after therapy. The doses of azithromycin used for treatment ranged from 4 to 30 g. Conclusions: The failure of azithromycin to cure a substantial number of patients with primary and secondary syphilis in Shanghai suggests that azithromycin has limited therapeutic value in this setting. the second in the nation. 14,266 cases were reported and 9073 cases were diagnosed as primary and secondary syphilis. 1 Prompt detection of infection and effective treatment are key elements to the control of syphilis. Penicillin has remained the recommended treatment for syphilis since its discovery more than 60 years ago. But penicillin requires special storage conditions and intramuscular or intravenous delivery, and can cause severe allergic reactions. Accordingly, a safe and simple alternative therapy has been sought, especially in resources constrained countries. Azithromycin is an azalide (macrolide) antimicrobial agent with a long half-life (68 hours), good tissue penetration, and excellent activity against Gram-negative organisms. 2-3 It has been successfully used as a single-dose, oral treatment for early syphilis. 4 - 9 However, a Treponema pallidum (T. pallidum) genotype consistent with macrolide resistance has been described in some patients with treatment failure, especially in patients with concomitant HIV infection. 10-16 In this report, we describe a large number of patients with syphilis who failed azithromycin therapy.

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.