Cytomegalovirus: should we screen pregnant women for primary infection?

Congenital cytomegalovirus (CMV) is a leading cause of neonatal morbidity, affecting ~0.5 to 1% of infants born each year. Primary maternal infection during early pregnancy is the greatest risk factor for severe neonatal morbidity/mortality. The current recommendation from national organizations advises against routine screening of pregnant women for primary infection. Recent advancements in diagnosis and treatment raise the issue of implementation of a national screening program. Prior to development of a major screening program for a highly prevalent and costly disease, the screening test must be safe, reliable, and valid with an effective and feasible intervention. This article reviews recent literature regarding available screening tests and potential interventions and whether criteria for a screening program are met in the current state of science. Although screening women using CMV immunoglobulin (Ig) G, IgM, and IgG avidity testing is reliable, effective intervention with hygiene modification or treatment with CMV-specific hyperimmune globulin is not as well established. More evidence from randomized controlled trials is needed prior to moving forward with a screening program for congenital CMV.

Society of Maternal-Fetal Medicine annual meeting and a continuing medical education course: results of pre- and postcourse survey.

OBJECTIVE: To assess the influence of a continuing medical education (CME) course on knowledge acquired and potential to change clinical management or opinion. STUDY DESIGN: During the annual Society of Maternal-Fetal Medicine meeting, a survey consisting of 11 knowledge-based, 10 management plan, and 8 opinion questions was administered at the start and completion of the CME course. Chi-square and Fisher exact test were used, and p < 0.05 was considered significant. RESULTS: The survey was administered electronically to 394 attendees. Questions assessing knowledge showed significant improvement with 91% (10/11) of queries. Purported management changed significantly with 60% (6/10) scenarios and opinions in 62% (5/8) of clinical situations. CONCLUSION: A survey done at the completion of a course indicates that CME improves knowledge and can change management and opinions. The prolonged benefits of CME need to be investigated.

HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication.

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) persists despite a vigorous virus-specific host immune response, and causes adult T-cell leukemia and lymphoma in approximately 2% of infected individuals. Here we report that HTLV-1 has evolved a genetic function to restrict its own replication by a novel post-transcriptional mechanism. The HTLV-1-encoded p30(II) is a nuclear-resident protein that binds to, and retains in the nucleus, the doubly spliced mRNA encoding the Tax and Rex proteins. Because Tex and Rex are positive regulators of viral gene expression, their inhibition by p30(II) reduces virion production. p30(II) inhibits virus expression by reducing Tax and Rex protein expression.

A comparison of 3 criteria of oligohydramnios in identifying peripartum complications: a secondary analysis.

OBJECTIVE: The objective of the study was to ascertain the diagnostic accuracy of 3 criteria of oligohydramnios in identifying 4 peripartum complications. STUDY DESIGN: The 3 definitions of oligohydramnios were amniotic fluid index (AFI) 5.0 cm or less and AFI <5% for gestational age (GA) using nomograms by Moore and Cayle or Magann et al. Likelihood ratio (LR) and guidelines by the Evidence-Based Medicine Working Group were used in the secondary analysis of previously published reports. AFI obtained during antepartum and intrapartum periods were analyzed separately. RESULTS: The 95% confidence intervals for the prevalence of oligohydramnios using the 3 criteria are significantly different in the antepartum or intrapartum analysis. The LR was <6 for ante- and intrapartum AFI to identify cesarean delivery for nonreassuring fetal heart rate tracing, Apgar score 3 or less at 5 minutes, umbilical arterial pH <7.00, and newborns' weight 5% or less for GA. CONCLUSION: The 3 criteria for determining the adequacy of amniotic fluid are not fungible, and they are not useful diagnostic tests for identifying peripartum complications because LR is <10.

Seizing of T cells by human T-cell leukemia/lymphoma virus type 1.

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) causes neoplastic transformation of human T-cells in a small number of infected individuals several years from infection. Several viral proteins act in concert to increase the responsiveness of T-cells to extracellular stimulation, modulate proapoptotic and antiapoptotic gene signals, enhance T-cell survival, and avoid immune recognition of the infected T-cells. The virus promotes T-cell proliferation by usurping several signaling pathways central to immune T-cell function. Viral proteins modulate the downstream effects of antigen stimulation and receptor-ligand interaction, suggesting that extracellular signals are important for HTLV-1 oncogenesis. Environmental factors such as chronic antigen stimulation are therefore important, as also suggested by epidemiological data. The ability of a given individual to respond to specific antigens is determined genetically. Thus, genetic and environmental factors, together with the virus, contribute to disease development. As in the case of other virus-associated cancers, HTLV-1-induced leukemia/lymphoma can be prevented by avoiding viral infection or by intervention during the asymptomatic phase with approaches able to interrupt the vicious cycle of virus-induced proliferation of a subset of T-cells. This review focuses on current knowledge of the mechanisms regulating HTLV-1 replication and the T-cell pathways that are usurped by viral proteins to induce and maintain clonal proliferation of infected T-cells in vitro. The relevance of these laboratory findings will be related to clonal T-cell proliferation and adult T-cell leukemia/lymphoma development in vivo.

Antimicrobial resistance of selected Salmonella isolates from food animals and food in Alberta.

Salmonella isolates (n = 209) obtained from food animals and foods in Alberta during 1996 through 1999 were tested for sensitivity to 17 antimicrobials. Of the 3553 antimicrobial susceptibility tests on Salmonella isolates, 11.8% were positive for resistance. These isolates were commonly resistant to tetracycline (35.4%), streptomycin (32.5%), sulfamethoxazole (28.7%), ticarcillin (27.3%), and ampicillin (26.8%). Resistance to at least 1 antimicrobial was observed in 112 isolates (53.6%). Salmonella Typhimurium, S. Typhimurium var. Copenhagen, and S. Heidelberg were the most common serovars among isolates resistant to individual antimicrobials and multiple antimicrobials. The most common profile of multiple-antimicrobial resistance was that which included resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline, and ticarcillin. The proportions of isolates that were resistant to antimicrobials were greater among bovine isolates of Salmonella than among poultry isolates, and this difference was greater among isolates from veterinary diagnostic sources than among those from monitoring sources.

Retroviral proteins that target the major histocompatibility complex class I.

The human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) retroviruses are two evolutionary distinct human pathogens. HTLV-1 is the etiologic agent of two diverse diseases: adult T-cell leukemia/lymphoma, as well as the neurologic disorder tropical spastic paraparesis/HTLV-1-associated myelopathy. HTLV-1 is the only retrovirus known to be the etiologic agent of human cancer. HTLV-2, the other known oncovirus, is not apparently associated with human cancer. While HTLV-1 transforms T-cells in vitro, HIV kills CD4+ T-cells and is the etiological agent of human acquired immunodeficiency syndrome, characterized by a progressive loss of CD4+ cells, weakening of the immune system, and susceptibility to opportunistic infections and cancer. HTLV-1 and HIV-1 both cause lifelong infections, which suggests that they have evolved mechanism(s) to evade detection by the host's immune response; particularly to evade cytotoxic T-lymphocytes, which play a major role in cellular immunity against viruses and will be the focus of this review.

The role of experience in the perception of phonetic detail in children's speech: a comparison between speech-language pathologists and clinically untrained listeners.

PURPOSE: This study examined whether experienced speech-language pathologists (SLPs) differ from inexperienced people in their perception of phonetic detail in children's speech. METHOD: Twenty-one experienced SLPs and 21 inexperienced listeners participated in a series of tasks in which they used a visual-analog scale (VAS) to rate children's natural productions of target /s/-/θ/, /t/-/k/, and /d/-// in word-initial position. Listeners rated the perceived distance between individual productions and ideal productions. RESULTS: The experienced listeners' ratings differed from the inexperienced listeners' ratings in four ways: They had higher intrarater reliability, showed less bias toward a more frequent sound, and were more closely related to the acoustic characteristics of the children's speech. In addition, the experienced listeners' responses were related to a different set of predictor variables. CONCLUSION: Results suggest that experience working as an SLP leads to better perception of phonetic detail in children's speech. Limitations and future research are discussed.

Caregiver-assisted coping skills training for patients with COPD: background, design, and methodological issues for the INSPIRE-II study.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a progressive illness characterized by airflow obstruction and dyspnea that afflicts over 12 million people and represents a leading cause of death in the United States. Not surprisingly, COPD is often associated with emotional distress and reduced psychosocial adjustment, which can negatively impact physical functioning and impair quality of life. However, the psychosocial consequences of COPD remain largely untreated. A previous randomized trial from our research team demonstrated that coping skills training (CST) can improve pulmonary-specific quality of life among pulmonary patients awaiting lung transplant (the INSPIRE study). To date, however, no studies have examined the effects of a caregiver-assisted CST intervention in patients with COPD with less severe disease. PURPOSE: INSPIRE II is a randomized clinical trial (RCT) funded by the NHLBI to evaluate the effects of telephone-based enhanced CST for patients with COPD and their caregivers compared to standardized medical care (SMC) including COPD education and symptom monitoring on medical outcomes, physical functioning, and quality of life. METHODS: Six hundred COPD patients and their respective caregivers recruited from Duke University and Ohio State University will be evaluated and randomized (in a 1:1 ratio) to enhanced CST (including sessions promoting physical activity, relaxation, cognitive restructuring, communication skills, and problem solving) or to SMC. The primary outcomes include all-cause mortality, COPD-related hospitalizations/ physician visits, and quality of life. These endpoints will be measured through self-report questionnaires, behavioral measures of functional capacity (i.e., accelerometer and six minute walk test) and pulmonary function tests (e.g., FEV(1)). RESULTS: This article reviews prior studies in the area and describes the design of INSPIRE-II. Several key methodological issues are discussed including the delivery of CST over the telephone, encouraging physical activity, and inclusion of caregivers as patient coaches to enhance the effectiveness of the intervention. LIMITATIONS: We recognize that SMC does not adequately control for attention, support, and non-specific factors, and that, in theory, non-specific effects of the intervention could account for some, or all, of the observed benefits. However, our fundamental question is whether the telephone intervention produces benefits over-and-above the usual care that patients typically receive. The SMC condition will provide education and additional weekly telephone contact, albeit less than the attention received by the CST group. We recognize that this attention control condition may not provide equivalent patient contact, but it will minimize group differences due to attention. We considered several alternative designs including adding a third usual care only arm as well as an education only control arm. However, these alternatives would require more patients, reduce the power to detect significant effects of our primary medical endpoints, and add a significant additional expense to the cost of the study that would make such an undertaking neither scientifically or financially viable. CONCLUSIONS: We believe that this novel approach to patient care in which caregivers are used to assist in the delivery of coping skills training to patients with COPD has the potential to change the way in which COPD patients are routinely managed in order to reduce distress, enhance quality of life, and potentially improve medical outcomes.

A novel chimeric Rev, Tat, and Nef (Retanef) antigen as a component of an SIV/HIV vaccine.

The human immunodeficiency virus type 1 (HIV-1) regulatory proteins Rev, Tat, and Nef are expressed at early time post-infection and represent attractive targets to be included in a vaccine candidate for AIDS. However, the putative immunosuppressive activities of some of these proteins may limit their immunogenicity. To circumvent these issues, a novel chimeric polyprotein vaccine candidate (Retanef), comprising genetically modified and re-assorted rev, tat, and nef open reading frames of simian immunodeficiency virus (SIV), was constructed and optimized for its expression in mammalian cells. Retanef encodes a protein of approximately 55 kDa localized primarily in the cytoplasm of transfected cells. The Retanef gene expressed in context of an eucaryotic expression vector (DNA-SIV-Retanef) or cloned into a highly attenuated poxvirus-based NYVAC vector (NYVAC-SIV-Retanef) was used to immunize either naive rhesus macaques or macaques chronically infected with SIVmac251 undergoing anti-retroviral therapy (ART). Three immunizations of naive macaques with DNA-SIV-Retanef followed by a single NYVAC-SIV-Retanef boost induced a response to the Mamu-A(*)01-restricted Tat epitope (Tat_SL8, TTPESANL) demonstrated by staining with a specific tetramer and by direct cytolytic activity assays, as well as responses to Rev, Tat and Nef proteins demonstrated by ELISPOT assays using overlapping peptide pools encompassing the entire proteins. Immunization of infected macaques with either DNA-SIV-Retanef or NYVAC-SIV-Retanef expanded the frequency of Tat-specific tetramer-staining cells by two- to seven-fold. No adverse effects were observed in either naive or SIV-infected rhesus macaques. Thus, an analogous HIV-1-based chimeric vaccine may represent useful component of an HIV-1 vaccine.