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.
3424059
Alterations in the hypothalamic pituitary adrenal axis during pregnancy and the placental clock that determines the length of parturition.
Although corticotrophin releasing hormone (CRH) was initially identified as a hypothalamic peptide it is also synthesised in the placenta and secreted into both the maternal and fetal circulation. The presence of large molecular weight forms in the placenta suggest that secretion may be constitutive rather that regulated. Placental CRH is bioactive but causes only modest increases in ACTH and cortisol in the pregnant woman because of agonist induced desensitisation of pituitary CRH receptors. CRH concentrations increase exponentially in maternal plasma as gestation advances. Elevated concentrations, compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve describing the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates indicating that CRH is linked to a placental clock which determines the length of gestation. Maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may prevent preterm labour. As significant CRH production by the placenta is restricted to primates future research must take into account the species specificity of the mechanisms regulating parturition.
19567920
The effect of repetitive haemorrhage on plasma cortisol, beta-endorphin and N-terminal pro-opiomelanocortin in conscious sheep.
We measured the effect of repeated haemorrhagic stress, performed on four consecutive days in conscious adult sheep, on the plasma concentrations of cortisol and ACTH-related peptides to determine whether the pituitary-adrenal response was altered by stress repetition. Peptides from the C-terminus of the ACTH pro-hormone was measured by beta-endorphin RIA. Glycopeptides derived from the N-terminus of the ACTH pro-hormone were measured by tau 3-MSH RIA. The immunoreactive tau 3-MSH in sheep plasma was found to have an apparent molecular weight of approximately 10,000 by gel chromatography through Sephadex G-75, which is similar to the size of the major circulating form of pro-tau-MSH found in human and rat plasma. Daily haemorrhage consistently elevated plasma concentrations of cortisol and pro-tau-MSH. There was no significant difference in the daily responses of either cortisol or pro-tau-MSH when considered individually. However, there was a significant change over the four days in the relationship between the cortisol and pro-tau-MSH responses, as judged by analysis of variance of the difference in daily z-scores of cortisol and pro-tau-MSH. This trend indicated a relative increase in the secretion of pro-tau-MSH from the pituitary compared to the cortisol response, and suggested that repeated exposure to stressful stimuli may alter the pituitary-adrenal-axis.
25322518
Corticotropin-releasing hormone in chimpanzee and gorilla pregnancies.
In humans, the length of gestation and the onset of parturition have been linked to the exponential production of placental CRH and a late gestational decline in maternal plasma CRH-binding protein (CRH-BP). CRH has been shown to have direct effects on the myometrium and on the fetal adrenal, where it stimulates production of the estrogen precursor dihydroepiandrosterone sulfate. In vitro placental CRH production is stimulated by cortisol and inhibited by progesterone. To determine whether this mechanism might operate in other apes, we sampled eight chimpanzees and two gorillas through their pregnancies for CRH, CRH-BP, cortisol, estradiol, progesterone, and alpha-fetoprotein. We show that both chimpanzee and gorilla maternal plasma CRH concentrations rise exponentially as observed in the human. The gorillas exhibited a human-like antepartum fall in CRH-BP, whereas CRH-BP in the chimpanzee remained stable. Pregnancy-associated changes in cortisol, estradiol, progesterone, and alpha-fetoprotein were qualitatively similar to those observed in humans. Maternal plasma cortisol correlated with plasma CRH in both gorillas (r = 0.60; P < 0.05) and chimpanzees (r = 0.36; P < 0.02). Further, there was a strong correlation between plasma estradiol and the log of plasma CRH in the gorilla (r = 0.93; P < 0.0001) and in the chimpanzee (r = 0.72; P < 0.001), which is consistent with the hypothesis that placental CRH determines the placental production of estradiol by stimulating the production of fetal adrenal dehydroepiandrosterone sulfate. Plasma CRH and progesterone were positively correlated providing no in vivo support for progesterone inhibition of CRH release.
36391510
Effect of histamine infusion on circulating methionine-enkephalin and catecholamine concentrations
In 5 normal adult men, histamine was infused i.v. for 5 min at 20 micrograms/kg/h and at 80 micrograms/kg/h on two occasions one week apart. Diastolic blood pressure fell and heart rate, plasma adrenaline and noradrenaline all rose in a dose-dependent manner, but plasma methionine-enkephalin (Met-Enk) concentrations were unchanged. These results indicate that while Met-Enk may be co-stored with catecholamines (CAs) in the adrenal medulla in at least this paradigm, circulating concentrations of CAs may be altered without similar changes in plasma Met-Enk immunoreactivity.
44367961
Recent advances in understanding the endocrinology of human birth
The timing of human birth has a crucial impact upon the survival of the fetus. New knowledge on the regulation of human birth includes the role of endogenous retroviruses in the formation of the syncytiotrophoblast cells and consequently the secretion of corticotrophin releasing hormone, a hormone linked to gestational length determination. miRNAs have been identified that mediate progesterone withdrawal at labor by suppressing progesterone-induced transcription factors. Progress has also been made in understanding how the contractile machinery of the uterine myocytes is activated at labor and the role of small heat-shock proteins in this process. From this work, new therapeutic targets have been identified that may be used to regulate the onset of labor and improve neonatal mortality.
39979651
Measuring the globalization of health services: a possible index of openness of country health sectors to trade.
Globalization is a key challenge facing health policy-makers. A significant aspect of this is trade in health services. However, little is currently known about how trade in health services will affect the health of populations and national economies. A key determinant of the impact of trade in health services will be the general economic and trade context of the country concerned. One specific aspect of this is the 'openness' of a country's health sector to trade; yet there is little, if anything, currently known about the most appropriate methods to assess openness of the health sector.
39397016
The relationship between reliability and size of willingness-to-pay values: a qualitative insight.
In a previous paper, the reliability of willingness-to-pay (WTP) values was found to be an increasing function of the size of WTP expressed. Here, the results of a qualitative exercise conducted alongside this quantitative study are presented. The results of this exercise suggest that higher WTP values may require more thought from the respondent which, in turn, gives them greater stability. At low levels of WTP, values appear to be taken from a 'discretionary account', where expenditure is more volatile. Caveats to this result, and suggestions for future research, are considered in the discussion.
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.
45170668
The relative sensitivity of willingness-to-pay and time-trade-off to changes in health status: an empirical investigation.
This paper directly compares the relative sensitivity of time-trade-off (TTO) and willingness-to-pay (WTP) values obtained for various levels of change in health status. This was achieved by administering a TTO and WTP survey to a population of 50 subjects, assessing their valuation of various degrees of change in health status. It was found that, overall, WTP is more sensitive than TTO in distinguishing between different dimensions of health at the same nominal level of health status (only four WTP values not significantly different, compared with eight TTO values). In addition, WTP was also more sensitive to differences in quality of life between different levels of health within each dimension (all values significantly different from each other, with TTO yielding three insignificant relationships). These results tentatively suggest, therefore, that WTP seems to be a more sensitive measure of change in health status than TTO.
41256785
It's not just what you do, it's the way that you do it: the effect of different payment card formats and survey administration on willingness to pay for health gain.
A general population sample of 314 Australian respondents were randomly allocated to complete a contingent valuation survey administered by face-to-face or telephone ('phone-mail-phone') interview. Although the telephone interview was quicker to complete, no significant difference was found in values obtained through either method. Within each sub-sample, respondents were also randomly allocated to the three different versions of the payment card (PC) questionnaire format: values listed from high-to-low, values listed from low-to-high and values randomly shuffled. The high-to-low version resulted in significantly higher values than the other versions. Further analyses indicate that the randomly shuffled PC version may produce the most 'valid' values.