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Biomedical subjects

S S Cohen

Publications and source records attributed to S S Cohen.

At least 19 recordsLinked to original sources

Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants.

Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1(Ba-L) infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08-4.77%). HIV-1-infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1-1 microg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1(Ba-L) (an R5 HIV-1 strain) more efficiently infected LC-T cell cocultures when compared with HIV-1(IIIB) (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1.

Anti-HIV Agents↗

Variant genotypes of FcgammaRIIIA influence the development of Kaposi's sarcoma in HIV-infected men.

Disturbances in inflammatory cytokine production and immune regulation coupled with human herpesvirus-8 (HHV-8) infection underlie the current understanding of the pathogenesis of Kaposi's sarcoma (KS), the most common HIV-associated malignancy. The low affinity Fc gamma receptors (FcgammaR) for IgG link humoral and cellular immunity by mediating interaction between antibodies and effector cells, such as phagocytes and natural killer cells. We examined the frequency of polymorphic forms of the low affinity FcgammaRs, FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB in 2 cohorts of HIV-infected men with KS and found that the FcgammaRIIIA genotype exerts a significant influence on susceptibility to or protection from KS. The FF genotype was underrepresented in patients with KS, whereas the VF genotype was associated with development of KS. A similar association was observed between FcgammaRIIIA genotypes and HHV-8 seropositivity. These observations suggest a possible role for FcgammaRIIIA in the development of KS during HIV infection.

Acquired Immunodeficiency Syndrome↗

Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge.

HIV infection is accompanied by an early immune dysfunction limiting host control of virus and likely contributing to difficulties in achieving a successful vaccine against HIV. We report here that the HIV Tat protein is strongly immunosuppressive, both immediately after immunization of mice with soluble protein (sTat), and in seroconverting humans, and propose that Tat-induced suppression cripples immune surveillance to HIV infection. We show that macrophages are sensitive to sTat stimulation at concentrations 1,000-fold lower (500 pM) than T cells, and this stimulation is accompanied by the immunosuppressive induction of Fas ligand on the macrophage. T cell proliferative defects induced by sTat in vitro can be completely (at lower concentrations of sTat) or partially (at higher concentrations) reversed by antagonists to Fas/Fas ligand interaction. We further report a method to preserve immunogenicity while inactivating Tat immunosuppression through oxidation, which advances the use of oxidized Tat as a component of an anti-HIV vaccine. These observations define additional methods to study the immunosuppressive functions of sTat that now may be rapidly applied to primary isolates from individuals with differing clinical courses. Our findings have immediate relevance for vaccine development, by describing and supporting a strategy that includes inactivated sTat in a multicomponent, anti-HIV vaccine.

AIDS Vaccines↗

Normal immune function of monocyte-derived dendritic cells from HIV-infected individuals: implications for immunotherapy.

Dendritic cells (DC) are the most potent cells involved in the generation of primary and secondary immune responses. To assess the feasibility of using autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, as well as DC obtained from HIV-uninfected (HIV-) individuals infected in vitro with HIV. After stimulation with recombinant CD40 ligand (CD40LT), cytokine and beta-chemokine production were similar by DC from HIV- donors infected in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uninfected DC from the same donors. Production of beta-chemokines, but not of cytokines, was increased by a CXCR4-using IIIB strain-infected DC (n = 7). Stimulation of HIV-infected DC with CD40LT decreased infection in Ba-L-infected DC, but had no effect on IIIB-infected DC. Consistent with this finding, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Monocyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced similar amounts of IL-12, IL-10, and beta-chemokines, following stimulation. By contrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and increased IL-10 production. In summary, phenotype, cytokine secretion, and beta-chemokine production by DC from HIV+ individuals were normal. These cells may prove useful in boosting cellular immune responses in HIV+ individuals.

Adoptive Transfer↗

Locus of control for general health and STD acquisition among adolescent girls.

PURPOSE: To examine adolescent girls' perception of control over general health and sexually transmitted disease (STD) acquisition. METHODS: Adolescents participating in a longitudinal study were asked questions regarding their perception of their locus of control. These questions, adopted from a previous measure, focused on six loci: internal control, control by parents, partners, peers, and health care providers, and chance. RESULTS: There were 128 girls (mean age, 17 years; range, 14.5 to 18.8); 82% were black and 18% white. Statistically significant associations were found between control of general health and STD acquisition for each locus of control subscale, with the exception of partner control. However, the girls reported significantly less control over STD acquisition than over general health for health care providers, parents, and by chance, and significantly more partner and internal control over STD acquisition than general health. The correlations between parental control over general health and over STD acquisition were inversely correlated with age. Partner control was positively related to current condom use, but internal control was not. CONCLUSIONS: The degree of the locus of control was specific for STD acquisition. Girls who believe they should be able to control STD acquisition may not be using condoms. The view of partners as having control over STD acquisition may represent joint communication or coercion. However, in general these findings support the development of female-controlled methods for STD prevention, such as topical microbicides.

Adolescent↗

No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris, or pemphigus foliaceus.

Paraneoplastic pemphigus has been associated with both malignancies and multicentric Castleman's disease; the latter is a rare angiolymphoproliferative disorder that has also been linked with human herpesvirus 8 (HHV8) infection. Other diseases definitively associated with HHV8 include Kaposi's sarcoma and primary effusion lymphoma. In a search for additional HHV8-associated diseases, patients with paraneoplastic pemphigus, as well as patients with pemphigus vulgaris and pemphigus foliaceus, were studied. Using an immunofluorescence assay able to specifically detect antibodies directed against lytically induced HHV8 antigens, HHV8 antibodies were not detected in sera from 24 patients with paraneoplastic pemphigus (including 10 with concomitant Castleman's disease) nor from 19 patients with pemphigus vulgaris. Sera from patients with Kaposi's sarcoma and from healthy U.S. blood donors were positive (25 of 26) and negative (none of 20), respectively. In addition, HHV8 DNA was not found in frozen lesional skin of five patients with pemphigus vulgaris and five patients with pemphigus foliaceus by nested polymerase chain reaction (lower limit of detection = 10 copies viral DNA per microg total cellular DNA). Finally, tissue sections of lesional skin from 10 patients with pemphigus vulgaris were negative for HHV8 by in situ hybridization, using probes able to detect both latently and lytically expressed HHV8 genes in Kaposi's sarcoma tissue. In summary, no evidence of HHV8 infection was found in all types of pemphigus using a variety of methods. These findings do not support a general role for HHV8 in skin diseases associated with immunosuppression.

Castleman Disease↗

Topical microbicides. Current status and research considerations for adolescent girls.

BACKGROUND AND OBJECTIVES: For sexually active adolescent girls, sexually transmitted diseases (STDs) represent a significant health problem. Although condom use may be an effective intervention against STDs in this high-risk population, actual use depends on the cooperation of the male partner. Therefore, the development of female-controlled methods such as topical microbicides have been endorsed as an important option for STD prevention. GOALS: This article reviews the current status of intravaginal microbicide development and discusses aspects of adolescent development that should be considered in topical microbicide research. RESULTS: Biological development, cognitive capacities, psychosexual maturation, and the sociocultural context are key features that affect the likelihood that adolescents will adopt microbicides as a specific methods of STD protection. CONCLUSION: Adoption of topical microbicides by adolescents will require an "adolescent friendly" perspective for topical microbicides to have a significant impact on the STD epidemic.

Administration, Topical↗

Focus groups reveal perils and promises of managed care for nurse practitioners.

Decades of practice and research suggest that nurse practitioners (NPs) provide cost-effective and high-quality care. Managed care's emphasis on prevention and cost savings led some policy makers to view NPs as a way to meet the need for primary care providers. However, access to and utilization of NPs has increasingly been controlled by managed care organizations (MCOs) through their selection of providers for primary care panels. This study employed qualitative methodology to examine NPs' experiences with MCOs. Three focus groups, comprising 27 NPs in New York and Connecticut, revealed NPs' mixed reactions to managed care and a range of sentiments regarding NPs' efforts to be listed as primary care providers. The results reflected NPs' concerns about their perceived "invisibility," as well as their sense of "invincibility" in the ways in which NPs are responding to the barriers posed by MCOs. They identified barriers to, as well as ways to facilitate, being listed by MCOs, and described the importance of NPs working individually and collectively in negotiating with MCOs.

Connecticut↗

Family involvement in the gynecologic care of adolescents.

The purpose of this paper is to address the issues of family involvement in gynecologic care for adolescent girls. This is accomplished by reviewing pertinent literature and its implication for health-care delivery. Specific aspects of adolescent development including changes in cognitive development and relationships are reviewed. In addition, the implications of communication between parent and adolescent, degree of parental monitoring, and the type of parenting style are discussed. Using this information as a background, recommendations for family involvement in gynecologic care are given. Methods for handling appointments are addressed; including the structure and content of the appointment and also the follow-up appointment, especially for high-risk families. Issues of confidentiality for both adolescent and parent are discussed. This information should aid clinicians in supporting those features of families that promote positive growth in adolescent girls.

Adolescent↗

Mild traumatic brain injuries in low-risk trauma patients.

BACKGROUND: Moderate or severe traumatic brain injury (TBI) resulting from cranial trauma is usually easily recognizable. Mild TBI (MTBI), however, may escape detection at presentation because of delayed symptoms and the absence of radiographic abnormalities. Despite its subtle or delayed presentation, the spectrum of symptoms often experienced after MTBI, collectively referred to as "postconcussive syndrome," may cause serious psychosocial dysfunction. METHODS/RESULTS: To assess the sensitivity of emergency department screening for MTBI, a prospective follow-up study was conducted on a group of patients (N = 129) who had been evaluated at a regional trauma center after blunt trauma. None had symptoms or signs of TBI at presentation, nor any history of direct cranial trauma. All were discharged to home from the emergency department without a diagnosis of TBI. At 1 month after injury, 41 of 129 (32%) patients described an increase in symptoms consistent with MTBI. The most common symptoms were insomnia (62%), headaches (58%), irritability (56%) and fatigue (56%). At 2 months, most symptoms had decreased significantly, and none had increased in severity. Despite improvement in their symptoms over that time period, 11% of those with persistent symptoms remained unable to resume their premorbid daily activities. CONCLUSIONS: These data, obtained from a population of patients considered to be at extremely low risk for TBI, indicate that MTBI occurs more often among blunt trauma patients than is commonly appreciated, even in busy trauma centers. Because early recognition of MTBI may expedite referral of these patients for appropriate outpatient follow-up care, thereby avoiding potentially serious social and financial repercussions, emergency department personnel should have a high index of suspicion for MTBI in any patient sustaining blunt systemic trauma. Current measures that screen for MTBI appear to be inadequate; follow-up protocols may prove to be more sensitive screening tools.

Adolescent↗

Developmental sophistication among adolescents of negotiation strategies for condom use.

Condoms are an important method of reducing the risk of sexually transmitted disease among sexually active adolescents. This study used a developmental approach to examine the negotiation of condom use. The Interpersonal Negotiation Strategy Interview was administered to adolescents using two vignettes that were focused on the negotiation of "safer sex" behaviors. The sample consisted of 196 girls and 92 boys recruited from their primary care clinic or Job Corps. The mean scores for each problem-solving step were at the subjective, unilateral stage, which indicates that problems are resolved through one-way methods. Current educational strategies and the lack of mutuality in adolescents' sexual relationships influence the level of negotiation skills. Interventions need to be at the appropriate developmental level but also need to encourage progress toward collaborative relationships.

Adolescent↗

Issues related to the sexual decision-making of inner-city adolescent girls.

To be effective in reducing the risks of sexual activity in adolescent girls, the context of adolescent sexuality needs to be understood. Two focus groups of high-risk inner-city African-American and Caucasian adolescent girls (15 to 16 years of age) were organized to explore issues related to sexual decision-making. The transcripts of the groups were reviewed for recurrent themes the girls discussed in regard to sexual decision-making, and their views of relationships and images of males. Verbatim examples are presented to exemplify each category. These adolescents experienced multiple pressures to engage in intercourse at young ages, but utilizing the presence of others was described as a helpful means to avoid engaging in sexual activities. The lack of mutual trusting relationships also was an important aspect for the these girls. Interventions which reduce the pressures to engage in sexual behaviours, develop methods for coping with these pressures, and facilitate the ability to establish mutual relationships will aid the healthy psychosexual development of adolescent girls.

Adolescent↗

Parents, peers, and the acquisition of an STD. Developmental changes in girls.

PURPOSE: The purpose of this study was to examine the relationship between age and number of sexually transmitted diseases (STD) episodes in sexually active girls with their perceptions of the interpersonal implications of STD acquisition. METHODS: The sample consisted of 248 girls (mean age = 16.9 years); 74% had an STD history. Adolescents responded to statements using a five-point Likert scale regarding their interpersonal expectations, and rated the perceived prevalence of STD among their friends and among all adolescents. RESULTS: The results of logistic regression analyses indicated that older girls were less likely to tell their parents but did not perceive parental support differently than younger girls. Older girls were more likely to tell their partners and to be more embarrassed by the acquisition. Those with a greater number of STD episodes perceived the acquisition as a less negative event. Girls with a greater number of STD episodes perceived the prevalence of STD to be significantly greater among their friends and among all adolescents than those girls with fewer episodes. Overall, the perceived prevalence among friends (40%) was significantly lower than the perceived prevalence among teens in general (74%). CONCLUSIONS: Future research and practice in aiding adolescent girls to manage STD acquisition must incorporate developmental theory, and, when appropriate, methods to involve families while preserving privacy.

Adolescent↗

Strategies for coping with sexually transmitted diseases by adolescent females.

Coping strategies of adolescent girls in response to the acquisition of a sexually transmitted disease (STD) were evaluated. Perceptions of control over acquisition of an STD and emotional impact were assessed. The sample consisted of 177 adolescent girls recruited from their source of primary care (mean age = 16.8). There were no differences in the use of coping strategies by age group or STD history. Subjects used a wide variety of coping strategies; those who viewed the future acquisition of an STD more negatively used more strategies. Wishful thinking was used by most of the subjects, but was not felt to be helpful; despite this, adolescents with a previous STD were no less likely to use wishful thinking. It was concluded that adolescent health care providers must understand girls' responses to STD and help them develop effective coping skills to reduce the incidence of STD.

Adaptation, Psychological↗

The OR suite as a unique trauma resuscitation bay.

Trauma is the fourth leading cause of death in the United States, and trauma injuries affect more than 50 million Americans annually. Inadequate care of trauma patients can cause unnecessary patient deaths. To decrease death and disability caused by trauma, one Denver hospital developed a trauma OR based on the "Golden Hour" principle (ie, the sooner a patient receives treatment, the more likely the patient will survive). Since 1977, this hospital has performed 1,838 trauma resuscitations in the trauma OR suite. This article discusses the importance of triage and recants the history of trauma patient transportation. The authors detail the trauma procedures at their hospital, including the specific roles of trauma team members and the necessary equipment, and provide demographic information on the trauma resuscitations performed at the hospital since 1988. The article also discusses the extensive and continuous orientation necessary for trauma team members and explains the quality improvement strategies implemented by this hospital.

Adolescent↗