Partial protection against chlamydial reproductive tract infection by a recombinant major outer membrane protein/CpG/cholera toxin intranasal vaccine in the guinea pig Chlamydia cavaie model

Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There currently is no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly involved using the murine model, however infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals. MOMP-specific IgG and IgA were present in the vaginal mucosae, and high levels of MOMP-specific IgG were detected in the serum of immunised animals. Antibodies from the vaginal mucosae were also shown to be capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with a live C. caviae infection of 102 inclusion forming units. We observed a decrease in duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP immunised animals, compared to animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract (URT) pathology in r-MOMP immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, not only by reducing chlamydial burden but also URT pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.

Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF

Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form of immunization to protect mice against genital tract and respiratory tract chlamydial infection. Protection was associated with local antibody responses in the vagina, uterus and lung as well as strong Th1 responses in the lymph nodes draining the reproductive tract and lungs respectively. In this study we show that topical application of GM-CSF to skin enhances the numbers and activation status of epidermal dendritic cells. Topical application of GM-CSF also increased the immune responses elicited by TCI. GM-CSF supplementation greatly increased cytokine (IFNgamma and IL-4) gene expression in lymph node and splenic cells compared to cells from animals immunized without GM-CSF. IgG responses in serum, uterine lavage and bronchoalveolar lavage and IgA responses in vaginal lavage were also increased by topical application of GM-CSF. The studies show that TCI induces protection against genital and respiratory tract chlamydial infections and that topical application of cytokines such as GM-CSF can enhance TCI-induced antibody and cell-mediated immunity.

The threat to scientific integrity in environmental and occupational medicine

Over the last century, environmental and occupational medicine has played a significant role in the protection and improvement of public health. However, scientific integrity in this field has been increasingly threatened by pressure from some industries and governments. For example, it has been reported that the tobacco industry manipulated eminent scientists to legitimise their industrial positions, irresponsibly distorted risk and deliberately subverted scientific processes, and influenced many organisations in receipt of tobacco funding. Many environmental whistleblowers were sued and encountered numerous personal attacks. In some countries, scientific findings have been suppressed and distorted, and scientific advisory committees manipulated for political purposes by government agencies. How to respond to these threats is an important challenge for environmental and occupational medicine professionals and their societies. The authors recommend that professional organisations adopt a code of ethics that requires openness from public health professionals; that they not undertake research or use data where they do not have freedom to publish their results if these data have public health implications; that they disclose all possible conflicts; that the veracity of their research results should not be compromised; and that their research independence be protected through professional and legal support. The authors furthermore recommend that research funding for public health not be directly from the industry to the researcher. An independent, intermediate funding scheme should be established to ensure that there is no pressure to analyse data and publish results in bad faith. Such a funding system should also provide equal competition for funds and selection of the best proposals according to standard scientific criteria.

Transport of IgG across the blood-luminal barrier of the male reproductive tract of the rat and the effect of estradiol administration on reabsorption of fluid and IgG by the epididymal ducts

In rats immunized systemically with tetanus toxoid the concentration of specific anti-tetanus-toxoid-specific IgG in fluid from the rete testis and cauda epididymidis were respectively 0.6% and 1.4% the concentration in blood serum. The extratesticular duct system reabsorbed 97% of the IgG and 99% of the fluid leaving the rete, but estradiol administration affected the site of reabsorption. In untreated rats, the ductuli efferentes reabsorbed 94% of the IgG and 96% of the fluid leaving the rete, whereas estradiol-treated rats reabsorbed 83% of the IgG and 86% of the fluid, and the ductus epididymidis fully compensated for these different effects of estradiol on the ductuli efferentes. The concentrations of IgG in secretions of the seminal vesicles and prostate gland were lower (0.1% and 0.3% respectively of the titers in blood serum) than in fluids from the extratesticular ducts, and were not affected by the administration of estradiol. RT-PCR showed that Fcgrt (neonatal Fc receptor, also known as FcRn) is expressed in the reproductive ducts, where IgG is probably transported across epithelium, being particularly strong in the ductuli efferentes (where most IgG was reabsorbed) and distal caput epididymidis. It is concluded that IgG enters the rete testis and is concentrated only 2.5-fold along the extratesticular duct system, unlike spermatozoa, which are concentrated 95-fold. Further, the ductus epididymidis can recognize and compensate for changes in function of the ductuli efferentes.

Emergency medicine in China

With the world’s largest population of 1.3 billion, China is a rapidly developing country. In line with this development, China’s enormous health system is experiencing an unprecedented series of reforms. According to a recent official government report, China has 300, 000 health organizations, which include 60, 000 hospitals and a total number of 3.07 million beds (China NBoSoP 2006). To provide health services for the national population, as well as the substantial number of visitors, China has 1.93 million doctors and 1.34 million registered nurses (China NBoSoP 2006). From 1984 to 2004, the number of inpatients grew from about 25 to 50 million, with outpatient figures increasing from 1.1 to 1.3 billion (China MoH 2006). The scale of the health system is likely bigger than in any other countries in the world, but the quality of medical services is still among the levels of developing countries. In 2005, approximately 3.8% of inpatients (about 1.5 million)(China NBoSoP 2006) were admitted because of injury and poisoning, which created significant load for the acute health system. These increased figures are at least partly because of the development of the health system and technological health-care advances but, even with such advances, this rapid change in emergency health-care demand has created a very significant burden on existing systems...

Significant Dot: The 1769 transit of Venus - a tale of astronomy, medicine and empire

This article places the 6 June 2012 transit of Venus in the context of James Cook’s voyage from England to the South Pacific to observe the 1769 transit of Venus. A description is given on how to use a computer program called Stellarium to ‘observe’ the 1769 transit of Venus exactly as Cook saw it from the island of Tahiti in the South Pacific.

Queensland Emergency Medicine Research Foundation: Special report

The development of any new profession is dependent on the development of a special body of knowledge which is the domain of the profession and key to this is the conduct of research. In 2007, as part of the settlement of an Enterprise Bargaining Agreement and following sustained lobbying by Emergency Physicians, the Queensland Government agreed to establish an Emergency Medicine Research Fund to foster the development of research activities in Emergency Medicine in Queensland. That fund is now managed by the Queensland Emergency Medicine Research Foundation. The aims of this article are to describe the strategic approaches taken by the Foundation and its first three years of experience, to describe the application of research funds and to foreshadow an evaluative framework for determining the strategic value of this community investment. The Foundation has developed a range of personnel and project support funding programs and competition for funding has increased. Ongoing evaluation will seek to determine the effectiveness of this funding strategy on improving the effectiveness of research performance and the clinical and organisational outcomes that may derive from that initiative.

Anticipating the use of life extension technologies : possible pointers from the adoption of assisted reproductive technologies

The first effective life extension technologies might well become available within the next few years. Experts from the University of Queensland, Australia, explore the possible public reaction to these therapies and the ethical and social concerns they raise, drawing on the experience of assisted reproduction technologies

Contraceptive changes after reproductive events among Australian women born in 1973 to 1978: A longitudinal study from 1996 to 2009

Background Women change contraception as they try to conceive, space births, and limit family size. This longitudinal analysis examines contraception changes after reproductive events such as birth, miscarriage or termination among Australian women born from 1973 to 1978 to identify potential opportunities to increase the effectiveness of contraceptive information and service provision. Methods Between 1996 and 2009, 5,631 Australian women randomly sampled from the Australian universal health insurance (Medicare) database completed five self-report postal surveys. Three longitudinal logistic regression models were used to assess the associations between reproductive events (birth only, birth and miscarriage, miscarriage only, termination only, other multiple events, and no new event) and subsequent changes in contraceptive use (start using, stop using, switch method) compared with women who continued to use the same method. Results After women experienced only a birth, or a birth and a miscarriage, they were more likely to start using contraception. Women who experienced miscarriages were more likely to stop using contraception. Women who experienced terminations were more likely to switch methods. There was a significant interaction between reproductive events and time indicating more changes in contraceptive use as women reach their mid-30s. Conclusion Contraceptive use increases after the birth of a child, but decreases after miscarriage indicating the intention for family formation and spacing between children. Switching contraceptive methods after termination suggests these pregnancies were unintended and possibly due to contraceptive failure. Women’s contact with health professionals around the time of reproductive events provides an opportunity to provide contraceptive services.

Data mining traditional Chinese medicine (TCM) lessons learnt from mining in law and allopathic medicine

Key decisions at the collection, pre-processing, transformation, mining and interpretation phase of any knowledge discovery from database (KDD) process depend heavily on assumptions and theorectical perspectives relating to the type of task to be performed and characteristics of data sourced. In this article, we compare and contrast theoretical perspectives and assumptions taken in data mining exercises in the legal domain with those adopted in data mining in TCM and allopathic medicine. The juxtaposition results in insights for the application of KDD for Traditional Chinese Medicine.

Fertility and infertility : studies in reproductive epidemiology in Australia

Worldwide, there are few large-scale epidemiological studies on infertility. In Australia, population-based research on infertility is limited to a few small-scale studies. Therefore, the prevalence of infertility and unmet need for specialist medical advice and treatment cannot be estimated reliably. Women who have used assisted reproductive technologies (ART) are recorded in treatment registries. However, there are many infertile women who are excluded from these clinical populations because they neither seek advice nor use treatment. The thesis was based on a biopsychosocial model of health and used the methods of reproductive epidemiology to address the lack of national data on the prevalence of infertility in Australia. Firstly, numbers of births and pregnancy losses were investigated in two generations of women participating in the Australian Longitudinal Study on Women’s Health (ALSWH). The ALSWH is a broad-ranging, longitudinal examination of biological, psychological and social factors that impact on women’s health and wellbeing. Women from three age cohorts were randomly sampled from the population using the universal public health insurance (i.e., Medicare) database and ALSWH participants were representative of the female population. However, the studies in the thesis only involved data from two cohorts. The younger cohort were born in 1973-78 and completed up to four mailed surveys between 1996 (when they were aged 18-23 years, n=14247) and 2006 (28-33 years, n=9145). The mid-aged cohort were born in 1946-51 and completed four mailed surveys between 1996 (when they were aged 45-50 years n=13715) and 2004 (53-58 years, n=10905). Compared to other studies that focus on outcomes of single pregnancies, these studies included all pregnancy outcomes by developing comprehensive reproductive histories for each woman. Pregnancy outcomes included birth, miscarriage, stillbirth, termination and ectopic pregnancy. Women in the youngest cohort (born in 1973-78) were only just reaching their peak childbearing years and many (44%) had yet to report their first pregnancy outcome. Women from the mid-aged cohort (born 1946-51) had completed their reproductive lives and 92% were able to report on their lifetime pregnancy outcomes. Pregnancy losses, especially miscarriage, were common for both generations of women. Secondly, the prevalence of infertility, seeking medical advice and using treatment was identified for these two generations of women. For the older generation, the lifetime prevalence of infertility and demand for treatment was investigated in the context of the specialist medical services which became available circa 1980. By this time, however, most of these older women had already been pregnant and completed their families. For women who experienced infertility (11%), their options for advice and treatment were limited and less than half (42%) had used any treatment. More recently for the younger generation of women, who were aged 28-33 years in 2006, specialist advice and treatment were extensively available. Among women who had tried to conceive or had been pregnant (n=5936), 17% had experienced infertility and the majority (72%) were able to access medical advice. However, after seeking advice only half of these infertile women had used treatment with fertility hormones or in vitro fertilisation (IVF). Overall for infertile women aged up to 33 years, only one-third had used these treatments. Thirdly, the barriers to accessing medical advice and using treatment for infertility were identified for women aged less than 34 years. Among a community sample of infertile women aged 28-33 years (ALSWH participants), self-reported depression was found to be a barrier to accessing medical advice. The characteristics of these infertile women in the community who had (n=121) or had not (n=110) used treatment were compared to infertile women aged 27-33 years (n=59) attending four fertility clinics. Compared to infertile women in the community, living in major cities and having private health insurance were associated with early use of treatment for infertility at specialist clinics by women aged <34 years. In contrast to most clinical studies of IVF, the final study reported in the thesis took into account repeated IVF cycles and the impact of women’s individual histories on IVF outcomes. Among 121 infertile women (aged 27-46 years) who had 286 IVF cycles, older age and prolonged use of the oral contraceptive pill were associated with fewer eggs collected. Further, women in particular occupations had lower proportions of eggs fertilised normally than women in other occupational groups. These studies form the first large-scale epidemiological examination of infertility in Australia. The finding that two-thirds of women with infertility had not used treatment indicates that there is an unmet need for specialist treatment in women aged less than 34 years. However, barriers to accessing treatment prevent women using ART at a younger age when there is a higher chance of pregnancy.