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.
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.
37019249
Acute hemorrhagic stress in conscious sheep elevates immunoreactive beta-endorphin in plasma but not in cerebrospinal fluid.
The effects of acute hemorrhagic stress on the concentrations of immunoreactive beta-endorphin (IR beta EP) in cerebrospinal fluid (CSF) and blood plasma were investigated in conscious sheep in which the cisterna magna, a carotid artery, and a jugular vein were chronically cannulated. Serial samples of CSF and jugular venous blood were collected before and after acute arterial hemorrhage and in control experiments. Basal concentrations of IR beta EP were higher in plasma than in CSF. Plasma concentrations of cortisol and IR beta EP increased within 45 min of the commencement of hemorrhage and returned to near baseline levels within 2.25 h. The concentrations of cortisol and IR beta EP in plasma observed after hemorrhage were significantly different from those observed in controls (analysis of variance). Neither the molar nor the relative changes from initial concentrations of IR beta EP in CSF were significantly different between hemorrhage-stressed and controls by analysis of variance. These results show that hemorrhagic stress in conscious sheep elevates concentrations of IR beta EP in plasma but not in CSF, indicating that pituitary beta EP secreted into blood does not enter CSF in significant amounts.
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.
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.
29843044
Hormone trajectories leading to human birth
The mechanisms regulating human parturition and labor remain unknown. This ignorance is expensive as preterm birth is responsible for 70% of neonatal mortality and 50% of cerebral palsy. Methods for the prediction of preterm birth and treatments for women in preterm labor have poor efficacy reflecting our limited knowledge of the mechanisms involved. Recent research has supported the view that parturition is a cascade of events that commences early in pregnancy and involves the mother, fetus, placenta, membranes, cervix and myometrium. Although a number of the key hormones and proteins involved have been identified, the relationships between these factors in time and tissues remain unclear. Placental production of Corticotropin-releasing hormone (CRH) is proposed as an early event regulating the cascade of events. Central to the onset of parturition will be a mechanism for progesterone withdrawal and estrogen activation in human. Two forms of progesterone receptor with opposing actions exist in the human myometrium. Progesterone receptor A (PR-A) is a dominant negative repressor of progesterone receptor B (PR-B). Preliminary studies strongly support the hypothesis that the onset of human parturition is initiated by rising concentrations of PR-A in the myometrium.
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.
27343241
Novel algorithms and the benefits of comparative validation
Contact: 2robsmith@gmail.com, jtprince@chem.byu.edu Bioinformatic research has produced a large volume of proposed algorithmic solutions to a host of problems. Whether presented as a processing step in a clinical experiment or treated in a stand-alone publication, novel bioinformatic algorithms are often not subjected to the thorough comparative evaluation endured by their counterparts in other closely related fields—such as computer science—where an algorithm unevaluated against extant methods is considered unpublishable. Two audiences are interested in algorithmic publications: the practitioner, who may use the algorithm, and the researcher, who will work to develop solutions superior to those extant. We argue that failure during the review/publication process to require comparative evaluation for novel algorithms is detrimental to both parties. To demonstrate the dilemma, we conducted a case study of novel LC-MS alignment algorithms. Of the 48 publications from 2001 to 2012 that present alignment algorithms of which we are aware, 60% include no comparison to other methods. Another 20%
19926226
Sensitivity to scale in contingent valuation: the importance of the budget constraint.
The possible insensitivity of willingness-to-pay (WTP) values to changes in scale continues to cause concern within the contingent valuation (CV) literature. Although several reasons for this phenomenon have been suggested, empirical evidence both supports and refutes insensitivity. This paper presents data that suggest that insensitivity may be significantly determined by the individual's budget constraint: the higher the proportion of income the expressed WTP represents, the greater the insensitivity of that WTP to changes in the scale of the good, irrespective of changes in underlying marginal utility. The methodological implication for CV studies in health care is outlined.
41950645
Beijing cough: a case report
Case PresentationUpon arrival in Beijing, China from London, England in 2008 a previously healthy 56-year old man developed a regular spasmodic cough for the duration of his stay in the city.
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.