The Australian longitudinal study of health and relationships

Background  

Ensuring the sexual and reproductive health of the population is essential for the wellbeing of a nation. At least three aspects of sexual and reproductive health are among the key policy issues for present Australian governments: maintaining and increasing the birth rate; reducing the abortion rate; and preventing and controlling Chlamydia infections.     

Child and Parent Response to the 1993 World Trade Center Bombing

This study evaluated children's symptoms 3 and 9 months after the 1993 bombing of the World Trade Center, and the relationship between parent and child reactions when only the children had been in the building. Nine children who had been trapped in an elevator, 13 who had been on the observation deck, and 27 controls completed the Posttraumatic Stress Reaction Index and a Fear Inventory. Parents completed these measures about the children and comparable measures about themselves. Exposed children reported posttraumatic stress disorder (PTSD) symptoms and disaster-related fears; their parents reported experiencing PTSD symptoms. Only parents rated children's symptoms as decreasing significantly over time. Association between child symptoms and parent symptoms increased over time. Children's initial distress predicted parents' distress 9 months postdisaster.     

Umbilical cord blood transplantation: current practice and future innovations

As a source of hematopoietic stem cells (HSCs), umbilical cord blood (UCB) has the advantages of speed of availability, tolerance of 1-2 antigen HLA mismatch, and a low incidence of severe GVHD. Thus, UCB represents a highly convenient HSC source that may significantly extend the HSC donor pool. UCB transplantation (UCBT) has become a standard practice in the treatment of pediatric malignancies. Now, UCBT is being investigated in adults using both conventional and non-myeloablative preparative regimens. As graft cell dose is the major factor determining hematopoietic recovery and survival in URD UCBT, methods to increase cell dose such as multiple-unit transplant and ex vivo expansion are being pursued. This review outlines the current status of UCBT with emphasis on current and future innovations.     

Family therapy and dialectical behavior therapy with adolescents: Part I: Proposing a clinical synthesis

Although the practice of family therapy in dialectical behavior therapy (DBT) with multiproblem suicidal adolescents is common and generally indicated, a particular model has yet to be delineated with this age group. The purpose of this article is to propose a coherent clinical synthesis of the more individually oriented DBT strategies with a broader family-systems orientation that maintains the integrity of both theoretical approaches while addressing the treatment needs of adolescents and their families. First, the authors briefly review the literature. Second, they describe the core dialectic of DBT, balancing acceptance and change, and its relevance to family therapy. Finally, the authors propose several specific acceptance and change strategies useful when implementing DBT family therapy with multi-problem adolescents.     

Endogenous gonadal hormones modulate behavioral and neurochemical responses to acute and chronic cocaine administration

Recent evidence demonstrates that there are sex differences in behavioral responses to cocaine. Further, reproductive gonadal hormones (estrogen, progesterone and testosterone) have been further implicated in mediating some of the cocaine-induced alterations. To better understand sex differences and the role of gonadal hormones in cocaine-induced locomotor and stereotypic behavior, intact and gonadectomized male and female Fischer rats were randomly assigned to either chronic cocaine (15 mg/kg) or saline treatments for 14 days followed by a challenge administration (7 days after the last cocaine/saline administration). Locomotor (ambulatory and rearing) and stereotypic activities were measured on days 1, 7 and 14 as well as after withdrawal/challenge with cocaine. Overall, intact female rats consistently showed a rapid (acquired by day 7) and longer lasting (persistent through the challenge dose) sensitization for all locomotor behaviors than any of the other groups. In contrast, intact males developed sensitization of these locomotor activities only in response to chronic cocaine administration, and after withdrawal and drug challenge the sensitization to cocaine-induced locomotor activity was no longer present. In female rats, gonadectomy affected ambulatory activity but not total and rearing responses after acute, sub-acute, chronic and challenge response to cocaine. On the other hand, castrated male rats were affected in cocaine-induced ambulatory activity but not rearing activity. In intact male rats, cocaine-induced stereotypic activity was rapidly and persistently sensitized after 7 days of cocaine administration, where gonadectomized male rats developed sensitization to cocaine-induced stereotypic activity only after a challenge cocaine administration. Although cocaine induced stereotypic activity, no statistically significant differences were observed between intact and ovariectomized female rats or throughout the different lengths of cocaine administration. After a challenge of cocaine, corticosterone levels were induced in all experimental groups. Moreover, no differences in levels of benzoylecgonine, a cocaine metabolite, were observed. Similar to our previous observations after acute cocaine administration, after challenge of cocaine, an increase in progesterone and a decrease in testosterone levels were observed in intact females and males, respectively. In summary, endogenous hormones seem to be involved in the behavioral activation and development of sensitization to cocaine.     

Complete mapping of a novel HLA A*6801-restricted HIV-1 Tat epitope directly with a rapid modified enzyme-linked immunospot assay

We identified a novel HLA A*6801-restricted HIV-1 Tat-derived cytotoxic T lymphocyte (CTL) epitope using an adapted enzyme-linked immunospot assay that allows the rapid ex vivo identification of CTL epitopes together with their associated HLA Class I restriction elements. The optimal 11 amino acid residue Tat epitope efficiently stabilized the refolding of monomeric peptide-HLA A6801 complexes in vitro and fluorochrome-labelled, tetrameric peptide-HLA A6801 complexes stained CD8 T cells specific for this epitope directly ex vivo.     

Combination therapy for postmenopausal osteoporosis

A number of agents have been shown to reduce the risk of fractures in patients with postmenopausal osteoporosis. However, the additional benefits of combination therapy as opposed to monotherapy are uncertain. We performed a MEDLINE search and reviewed the published randomized trials of agents used in combination. Combination therapy results in greater gains in bone mineral density than monotherapy and possibly greater effects on bone turnover. However, none of these studies are large enough or of sufficient duration to determine whether a greater reduction in fracture is achieved. Combination therapy has important cost implications and is likely to be associated with an increased prevalence of adverse events, reduced tolerability and a reduction in adherence. Furthermore, over-suppression of bone turnover as a result of combination antiresorptive therapy might have adverse effects on bone strength, particularly with long-term treatment. Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence.     

Understandings of risk among HIV seroconverters in Sydney

This paper examines the risk discourses of Sydney gay men who had recently become HIV positive. 92 in depth interviews were conducted eliciting narratives about the incident in which they believed they became infected. The veracity of this narrative was negotiated between the interviewer and participant. Qualitative analysis was performed in order to distinguish different styles of thinking and acting in relation to risk. Two overarching discourses were distinguished that broadly related to the fields of public health, HIV prevention education, social theory and health policy. These we characterise as ‘quantifiable/objectivist’ and ‘social/subjectivist’. The first approach sees risk as objectively knowable through the application of scientific method or reasoned thinking. The second regards actors as culturally embedded in relation to risk, itself a cultural category. The fact that all men in this study became infected demonstrates the potential fallibility of both approaches. HIV prevention strategies need to take account of both the cultural aspects of risk, understanding the embedded quality of everyday cultural practices such as hygiene, and understand these assumptions are often inadequate for preventing HIV infection. Objectivist approaches also entail problems as many men using them felt HIV infection to be inevitable or unavoidable in some circumstances.     

Solid-phase immunoassays in mechanism-based drug discovery: their application in the development of inhibitors of the molecular chaperone heat-shock protein 90

High-throughput screening of chemical libraries and the subsequent rapid progress of hit compounds through an iterative developmental test cascade are essential parts of modern molecular mechanism-based drug discovery. These processes depend on the use of efficient assay technologies and equipment. Enzyme-linked immunosorbent assays have historically been carried out in 96-well microtitre plates. Improvements in reagents and assay technologies mean that solid-phase immunoassays can be adapted for higher throughput to play an important role in modern drug discovery. The molecular chaperone heat-shock protein (Hsp) 90 is an important anticancer drug target because it maintains the conformation, stability, and function of many important oncogenic client proteins, including those involved with signal transduction, cell proliferation, survival, differentiation, motility angiogenesis, and metastasis. Using the standard inhibitors of the adenosine triphosphatase (ATPase) activity of Hsp90, geldanamycin (GA) and 17-allylamino-17- demethoxygeldanamycin (17AAG), novel solid-phase immunoassays have been validated using a time-resolved fluorescence (TRF) end point. Their utility for confirming the mechanism of action of Hsp90 inhibition in secondary cell-based assays has been shown and applied to the novel Hsp90 inhibitor CCT018159. Adaptation of these assays for later studies using human tumour xenografts and samples obtained from a Phase 1 trial of 17AAG is also described. Finally, comparison is made between the use and applicability of this type of immunoassay and other techniques such as western blotting, immunohistochemistry, and flow cytometry analysis.