Heat-shock protein 70 acts as an effective adjuvant in neonatal mice and confers protection against challenge with herpes simplex virus

Immunization of the neonate is a highly desirable goal for vaccine developers, since the neonate is profoundly susceptible to a number of viral and bacterial pathogens. The neonatal immune system tends to generate Th2 recall responses, known as neonatal tolerance, which may not protect against viral challenge later in life. In this study we demonstrate that a potent immune proinflammatory stimulator, heat-shock protein 70 (hsp70), can act as an effective and safe adjuvant in neonates. Priming of neonates with hsp70 coupled to a viral MHC Class I-restricted epitope (gB498-505) and injection with recombinant gB generated strong cytotoxic T lymphocyte (CTL) responses and a Th1 primary T helper cell response during the neonatal period. In addition, enhanced CTL and predominant Th1 recall responses to viral antigens were observed following secondary challenge as adults. These responses were sufficient to allow protection against a lethal challenge with Herpes Simplex Virus Type-1 (HSV-1). Therefore, hsp70 in conjunction with viral epitopes and recombinant viral protein can perhaps prime protective immune responses to herpes viruses early in life when infection, which can be life-threatening, and the establishment of latency frequently occur.     

The association of parity with mortality outcomes among triplets

OBJECTIVE: The purpose of this study was to evaluate the association of parity with stillbirth and neonatal and infant death among triplets. STUDY DESIGN: This was a retrospective cohort study of 15,930 triplets who were delivered in the United States between 1995 and 1997. Infants of nulliparous mothers were compared with infants of multiparous mothers. Adjusted relative risks for death by parity were computed with the use of the generalized estimating equations framework. RESULTS: The likelihood for stillbirth (odds ratio, 3.40; 95% CI, 2.20-5.26) was significantly greater among nulliparous mothers. Neonatal (odds ratio, 1.17; 95% CI, 0.95-1.43) and infant mortality rates (odds ratio, 1.10; 95% CI, 0.92-1.32) were comparable, however. With an increase in parity, there was a consistent declining trend in the risk for stillbirth (P<.0001). CONCLUSION: Nulliparity more than triples the risk for intrauterine fetal death among triplets. This parity-related disparity underscores the need for care providers to be particularly concerned about triplet gestations among nulliparous mothers.     

Towards a cognitive model and measure of dissociation

Dissociation comprises a range of psychological processes, which have largely been the subject of psychodynamic discussion. Dissociative phenomena are for the most part unaddressed by cognitive theorists. Current measures are atheoretical and our understanding of dissociation has been hampered by the absence of clear psychological models. This paper describes a new cognitive model of dissociation and the development and validation of a theoretically based measure-the Wessex Dissociation Scale (WDS). The WDS has adequate internal consistency, shows convergent validity with the Dissociative Experiences Scale (DES-II), and is equivalent to the DES-II in its associations with severe psychopathology. However, the WDS has some advantages over the DES-II, in that it is sensitive to milder manifestations of dissociation, demonstrating links to less severe pathologies. The findings described here provide preliminary support for the usefulness of the cognitive model, and the varied consequences of dissociative processes. The clinical and research utility of the model and the scale are discussed.     

What we have learned about conducting randomized controlled trials in the NICHD MFMU network

The National Institute of Child Health and Human Development (NICHD) created the NICHD Maternal Fetal Medicine Units Network in 1986 to conduct randomized trials and observational studies in perinatal medicine to improve adverse pregnancy and infant outcomes. From 1986 to 2002, the Network has started 16 randomized trials. Five of the trials are described, with particular attention given to difficult issues that arose, such as feasibility, sample size estimation, randomization in very high risk pregnancies, changing clinical practice, importance of the study question to the investigators, and lack of recruitment. Changes that the Network group made to their organization and methodology as a result of these issues are described, together with their application to some of the other trials proposed and conducted by the group.     

Data monitoring and safety committees and their operations

The scientific burden of proof for new therapies and technologies in obstetrics and gynecology has risen steadily over the past 15 to 20 years, and the randomized clinical trial has become integral to this higher standard. Data monitoring and safety committees are now critical components of clinical trials, yet their history, rationale, methods of operation, and overall role have not been well-characterized in the obstetrics and gynecology literature. In this review, an overview of the important and evolving role of data monitoring and safety committees is provided. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe what a data monitoring and safety committee is, plan who should comprise the DMSC, and outline the functions of a DMSC.