21610567
Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor.
CONTEXT
Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear.


OBJECTIVES
Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P.


DESIGN AND SETTING
A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital.


PATIENTS
Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained.


MAIN OUTCOME MEASURES
CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed.


RESULTS
CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07).


CONCLUSIONS
The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.
40275488
The nonsuppressibility of plasma cortisol persists after pregnancy.
To determine if normal balance is restored to the hypothalamic-pituitary-adrenal axis after pregnancy, we compared the dexamethasone suppressibility of plasma cortisol in women four days after delivery of their infant, with that of nonpregnant women. Plasma concentrations of cortisol before dexamethasone administration were similar in the post-partum women and in women taking oestrogen contraceptives, but both were higher than in normally cycling women. After dexamethasone, plasma cortisol in the post-partum women was significantly higher than in both oestrogen-taking and normally cycling nonpregnant women. The reduced dexamethasone-suppressibility of plasma cortisol, which is characteristic of pregnancy, extends into the post-partum period.
11517691
Pathological interactions with the timing of birth and uterine activation.
The physiological processes that regulate the onset of parturition and birth are slowly being elucidated, and the points at which pathology can intervene are becoming more apparent. The data support the view that multiple pathways lead to myometrial activation. The clinical corollary is that combinations of tocolytics that operate via different mechanisms may be more effective than single agents. It may also be necessary to divide preterm labour into groups based on underlying mechanisms and to tailor therapy accordingly.
37781778
[Free radicals and ailing proteins--the culprits behind Parkinson disease?].
Parkinson's disease is one of the most common neurodegenerative diseases, and affects approximately 1% of the population over 65 years of age. Many different insults appear to be involved in the etiology of the disease, among them environmental toxins and mitochondrial dysfunction. During the past five years, mutations in five different genes have been linked to rare, familial forms of Parkinson's disease. One of the mutated proteins, alpha-synuclein is normally implicated in synaptic plasticity and vesicle function. Dysfunction of this protein might lead to increased cytoplasmic dopamine levels. Since cytoplasmic dopamine is readily prone to autooxidation and enzymatic degradation--processes which generate reactive oxygen species--failure to properly store dopamine into vesicles might lead to oxidative stress. Indeed, nigral tissue from idiopathic Parkinson's disease patients shows signs of oxidative damage. In this article we propose that dopamine-induced oxidative stress might be a common final pathway in the pathogenesis of the disease.
13856154
Macroeconomic impact of pandemic influenza and associated policies in Thailand, South Africa and Uganda
BACKGROUND
Research has shown the value of conducting a macroeconomic analysis of the impact of influenza pandemics. However, previous modelling applications focus on high-income countries, and there is a lack of evidence concerning the potential impact of an influenza pandemic on lower- and middle-income countries.


OBJECTIVES
To estimate the macroeconomic impact of pandemic influenza in Thailand, South Africa and Uganda with particular reference to pandemic (H1N1) 2009.


METHODS
A single-country whole-economy Computable General Equilibrium (CGE) model was set up for each of the three countries in question and used to estimate the economic impact of declines in labour attributable to morbidity, mortality and school closure.


RESULTS
Overall GDP impacts were less than 1% of GDP for all countries and scenarios. Uganda's losses were proportionally larger than those of Thailand and South Africa. Labour-intensive sectors suffer the largest losses.


CONCLUSION
The economic cost of unavoidable absence in the event of an influenza pandemic could be proportionally larger for low-income countries. The cost of mild pandemics, such as pandemic (H1N1) 2009, appears to be small, but could increase for more severe pandemics and/or pandemics with greater behavioural change and avoidable absence.
24512083
Effects of Perinatal HIV Infection and Associated Risk Factors on Cognitive Development Among Young Children
OBJECTIVE. We examined the effect of HIV, in combination with other important health and social factors, on the development of cognitive abilities of children perinatally exposed to HIV. METHODS. Serial cognitive assessments were performed for 117 children who were infected vertically and 422 children who were exposed to but not infected with HIV, in a multicenter, natural history, longitudinal study. Repeated-measures analyses were used to evaluate the neurocognitive development of children between the ages of 3 and 7 years, as measured by the McCarthy Scales of Children’s Abilities (MSCA). RESULTS. Children with HIV infection and class C status scored significantly lower in all domains of cognitive development, across all time points, than did those who were HIV infected without an AIDS-defining illness and those who were HIV exposed but not infected. There were no significant differences between the 2 latter groups in General Cognitive Index or specific domain scores. Rates of change in cognitive development were comparable (parallel) among all 3 groups over a period of 4 years. Factors that were associated consistently and significantly with lower mean scores were HIV status, number of times an examination had been completed previously, primary language, maternal education, and gender. No factors were related to rate of change of any mean domain score. CONCLUSIONS. An early AIDS-defining illness increased the risk of chronic static encephalopathy during the preschool and early school age years. Children with HIV infection but no class C event performed as well as noninfected children in measures of general cognitive ability. No significantly different profiles of strengths and weaknesses for verbal, perceptual-performance, quantitative, or memory functioning were observed among children with or without HIV infection. A number of factors were found to have significant effects on the mean scores of children in all 3 groups; however, they were not related to the rate at which learning occurred.
17501143
The economy-wide impact of pandemic influenza on the UK: a computable general equilibrium modelling experiment
Objectives To estimate the potential economic impact of pandemic influenza, associated behavioural responses, school closures, and vaccination on the United Kingdom. Design A computable general equilibrium model of the UK economy was specified for various combinations of mortality and morbidity from pandemic influenza, vaccine efficacy, school closures, and prophylactic absenteeism using published data. Setting The 2004 UK economy (the most up to date available with suitable economic data). Main outcome measures The economic impact of various scenarios with different pandemic severity, vaccination, school closure, and prophylactic absenteeism specified in terms of gross domestic product, output from different economic sectors, and equivalent variation. Results The costs related to illness alone ranged between 0.5% and 1.0% of gross domestic product (£8.4bn to £16.8bn) for low fatality scenarios, 3.3% and 4.3% (£55.5bn to £72.3bn) for high fatality scenarios, and larger still for an extreme pandemic. School closure increases the economic impact, particularly for mild pandemics. If widespread behavioural change takes place and there is large scale prophylactic absence from work, the economic impact would be notably increased with few health benefits. Vaccination with a pre-pandemic vaccine could save 0.13% to 2.3% of gross domestic product (£2.2bn to £38.6bn); a single dose of a matched vaccine could save 0.3% to 4.3% (£5.0bn to £72.3bn); and two doses of a matched vaccine could limit the overall economic impact to about 1% of gross domestic product for all disease scenarios. Conclusion Balancing school closure against “business as usual” and obtaining sufficient stocks of effective vaccine are more important factors in determining the economic impact of an influenza pandemic than is the disease itself. Prophylactic absence from work in response to fear of infection can add considerably to the economic impact.
1484363
Public health evaluation in the twenty-first century: time to see the wood as well as the trees.
This paper argues that concepts, methodologies and practices within public health need further development if they are to be sufficient to allow us to develop, undertake and evaluate interventions in the twenty-first century. The public health profession, and the disciplines that contribute to it, maintains the historical focus upon detailed micro analysis (individual and health sector) and not broader macro analysis (societal and system). This brief paper suggests why this is and outlines three challenges it poses: specifying and evaluating outcomes; specifying and understanding complex causal pathways in social interventions and the development of multisector evaluation, to meet information demands from multiple stakeholders. While there is general agreement that public health evaluation needs development, this paper argues that the focus needs to be more upon a broader evaluative space than is currently practiced. There is a need to move beyond primary and secondary health-related effects upon individuals, and focus more on evaluation of the wider range and distribution of direct and indirect effects upon individuals, communities and populations. That is, those involved in public health evaluation need to step back and first consider the wood before focusing in on specific trees.