There is increasing evidence that cAMP promotes the relaxation of the myometrium, and other types of smooth muscle via the activation of cAMP-dependent protein kinase and other intracellular signalling pathways. The data from the first part of this study show that cAMP reduces the expression of most of the labour-associated gene, such as oxytocin receptor (OTR) (via PKA) and FP receptor. Interestingly, cAMP induces COX-2 expression via MAPK pathway. Therefore, with the exception of the COX-2 data, these findings suggest that cAMP agonists have the potential to be effective tocolytic agents. Most researchers also believe that progesterone plays an important role in maintaining uterine quiescence throughout pregnancy by inhibiting the expression of contraction-associated proteins in the myometrium. However, the exact mechanism responsible for the progesterone-induced inhibition of labour-associated genes expression remains unclear. Clinically, progesterone treatment has been shown to reduce the risk of preterm labour (PTL) in high-risk populations. Surprisingly, progesterone had no effect on the occurrence of preterm labor in multiple pregnancies. So the second part of this project focused on the hypothesis that cAMP could enhance the myometrial response to progesterone. The combined effects of cAMP and progesterone on the activation of different pathways in primary cultures of human myometrial cells was studied. It was found that forskolin enhanced the progesterone-induced expression of genes such as FKBP5 and 11βHSD1. The forskolin effects included the up-regulation of progesterone receptor (PR)-B levels and enhanced progesterone-driven activity of a progesterone response element (PRE) as well as increased PR-B binding to the PRE. The data also show that forskolin attenuate the association between PR and NCoR. Knockdown of NCoR blocks the ability of forskolin to enhance progesterone driven PRE activity. Furthermore, the ability of progesterone to repress IL-1β-induced COX-2 expression was enhanced by forskolin, which was associated with a delay in IL-1β-induced nuclear phospho-p65 entry, as well as an increase in IκB synthesis and a reduction in NF-κB binding to the COX-2 promoter. Overall, these data identify important interactions between cAMP and progesterone pathways that control myometrial expression of labour-associated genes and point towards a novel role for cAMP agonists to supplement progesterone-based clinical protocols in the treatment of PTL.

No description available.

This thesis explores the occupational structure and culture of urban midwifery practice in early modern Germany between 1650 and 1810. Following the Thirty Years War many larger cities began to reform midwifery provision. They were motivated partly by depopulation anxieties and partly by burgeoning civic confidence and prosperity. In the late seventeenth and early eighteenth century the Leipzig Council began to appoint midwife apprentices, introduced a municipal obstetrician (Stadtaccoucheur) to supervise its licensed midwives and carry out difficult operative deliveries, and began to provide its midwives with formal anatomical and obstetric instruction through the new Stadtaccoucheur. Drawing on municipal council records in the city of Leipzig, this thesis traces the varieties and forms of midwifery practice that existed within the urban setting and examines the impact of these reforms on the traditional culture of urban midwifery. It explores the structure of formal and informal midwifery, the socioeconomic and life cycle of midwives, client networks and the way in which midwives demarcated their occupational territory amongst themselves and with other practitioners. This thesis argues that these reforms were not driven by the state but were rather motivated by the Leipzig Council, the citizenry and midwives themselves. Moreover, these reforms served to reinforce rather than change the existing occupational structure and culture of urban midwifery in Leipzig, which was grounded in the moral economy of livelihood.

This thesis examines the diffusion of obstetric ultrasound technology in Scotland, from the early 1960s through to the end of the 1980s. Although the origins of obstetric ultrasound can be traced to 1955, and the pioneering work undertaken by Professor Ian Donald and his colleagues in Glasgow on the gynaecological applications of ultrasound, it was not until the early 1960s that the pathologies associated with pregnancy were directly investigated. Over the next thirty years, the technology underwent a number of significant transformations - in technical design, application and use, and organisation. The main focus of this thesis is on the uptake and implementation of obstetric ultrasound in new locations across Scotland, and on the dynamics of change associated with its use in clinical practice. U sing a case-study approach which centres on four individual Scottish hospitals, this thesis traces the complexity and heterogeneity evident in the diffusion of this technology. The definition of 'technology' employed in this thesis is three-dimensional - comprising of technical, cognitive and interactive/performative dimensions. Here it is argued that all three of these dimensions compose a technology, and that all three are open to adaptation and change, thus essentially changing the nature of the technology itself. This is highlighted through a comparative account, focussing on site-specific differences in the development, organisation and use of the technology. The evidence presented here has been drawn from a variety of historical sources. The recollections of a number of actors involved in the introduction, use and development of obstetric ultrasound in Scotland, as well as of women who experienced ultrasound during their pregnancies, have been collected using semi-structured interviews. To this oral history has been added information from a variety of archival sources held at the British Medical Ultrasound Society's Historical Collection (housed at The Queen Mother's Hospital, Glasgow). These include specialist professional journals, correspondence relating to ultrasound, manufacturers' literature, draft versions of key published papers, transcripts of interviews with prominent actors in the field and material donated by ultrasound workers across Scotland. Furthermore, the Collection also boasts a wide array of visual information (including pictures of various types of ultrasound equipment and images generated from them) and artifacts (ultrasound machines dating from the 1950s through to the 1980s). These, less conventional, historical sources are also employed in this thesisIn this comparative study of the diffusion of ultrasound, three related arguments are presented. Firstly, it is argued that innovation and diffusion are not mutually exclusive terms or periodising concepts, but are interwoven processes and forms of activity. The diffusion of obstetric ultrasound did not signal the 'end' of innovation, but merely the point at which new actors in new locations undertook it. Innovation is a crucial component in adapting a technology to new circumstances, users or contexts and thus it is argued that innovation and diffusion are inter-related, mutually dependent forms of interested human action. Secondly, obstetric ultrasound is characterised in this thesis as an emergent phenomenon, shaped by both technical and social factors. When the development of this technology is examined in a variety of historical and spatial contexts, it is evident that the form it takes is determined by the interplay of social factors (professional relationships and interests, actors interpretations of technology, etc.) and more technical or material factors (the way a machine responds to new demands or itself requires certain types of human or social response). Thus a complete account of the diffusion of obstetric ultrasound necessitates an approach that considers both social and material influences on technological change. Finally, this thesis explores the significance of site-specific local arrangements for the shaping of obstetric ultrasound. Interactions with technology take place within specific historical and locational settings. The specific character of each setting can affect the nature of inter-professional relationships, the organisation and administration of the technology, the characteristics of the patient population, and so on. Thus, the diffusion of obstetric ultrasound and the form that it takes in each new location are partly shaped by the way in which the technology interacts with new environments

published_or_final_version / Medicine / Master / Doctor of Medicine

There is a large decrease in endogenous estrogen production with menopause associated with increases in severity of risk factors for coronary heart disease (CHD), including lower high density lipoprotein cholesterol (HDL-C) concentrations. Exogenous estrogen is administered to decrease the risk of CHD. This project was designed to examine the influence of hormone replacement therapy (HRT), ethnicity, and body composition on cholesterol ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) activities, two enzymes involved in HDL metabolism. 205 women participated, 32% of Hispanic origin and 52% not presently undergoing HRT (58% Anglo, 39% Hispanic). CETP and LCAT activities were quantified by a mass transfer method and body composition variables were measured by dual energy x-ray absorptiometry and anthropometry. There were no significant differences in plasma lipids and lipoproteins among HRT groups (non-users, unopposed estrogen, combined therapy). Hispanic women had lower HDL-C concentrations and total plasma cholesterol to HDL-C ratio, and higher triglyceride concentrations and greater susceptibility of low density lipoprotein particles to oxidation. CETP activity was elevated in Hispanic women when compared to Anglo women. The ethnic difference in CETP activity was eliminated once IAAT or measures of trunk fat, but not total body fatness, were controlled. No differences in CETP or LCAT activities were found among HRT groups. Women not undergoing HRT tended to have greater abdominal fat compared to women undergoing either hormone therapy, however differences were not significant. Hispanic women had significantly greater amounts of abdominal fat than did Anglo women, even after adjusting for total body fat. CETP and LCAT activities were positively related to plasma lipids, lipoproteins (exception: negative association with HDL-C), and body composition. Correlations were higher with regional fat measures than with total body fat measures. In conclusion, HRT did not affect CETP or LCAT activities. Results suggest that associations between HRT use and decreased risk of CHD involve other mechanisms. Hispanic women had higher CETP activities and greater distribution of abdominal body fat suggesting that they are at greater risk for CHD compared to Anglo women.

No description available.

We estimated the effect of caffeine intake from tea, coffee, and colas on the risk of mild and severe intrauterine growth retardation (IUGR) through a case-control study in 500 live singleton infants born at Sainte-Justine Hospital, in Montreal, between May 1998 and July 2000. Cases of IUGR as well as one sex, race and gestational age-matched control per case were identified at birth. Data were abstracted from medical charts and post-delivery questionnaires, and were analysed using conditional logistic regression. Average caffeine intake in pregnancy was not a significant predictor of mild or severe IUGR (for mild IUGR, OR for >300 mg/day of caffeine vs. none:1.21, 95%CI [0.33, 4.40]; trend: p = 0.28). Moderate first-trimester caffeine use significantly increased the risk of mild (OR 2.41, 95%CI [1.01, 5.75]), but not severe, IUGR. Reduction of caffeine use at the onset of pregnancy was protective for mild and severe IUGR (OR 0.34, 95%CI [0.13, 0.92], and 0.55, 95%CI [0.32, 0.94], respectively).

Using a rat model, it has been demonstrated that C-section birth and birth hypoxia have long-term effects on several CNS parameters. While previous studies have used decapitated dams to perform C-sections, the purpose of experiment 1 was to develop a more clinically relevant model using controlled amounts of anesthetic. The findings show that the level of maternal anesthesia used is an important factor influencing neonatal systemic and CNS oxygenation during C-section birth. In experiment 2 indicators of systemic and CNS hypoxia were measured in rat born by C-section with varying concentrations of anesthetic and periods of added global anoxia. Anesthesia was shown to reduce the rate of recovery from global anoxia. Experiment 3 was designed to determine if different rat strains were differentially vulnerable to the long-term effects of C-section birth on amphetamine-induced locomotor activity. The findings from this study indicate that genetic factors and C-section birth interact in producing long-term CNS effects. The findings presented show how variations in birth procedure and genetic factors might interact to cause long-term alterations in CNS function.

Early embryo losses are characterized by a large infiltration of cnacrophages and NK-cells in the decidua surrounding resorbing embryos. This infiltration is combined with a high expression of interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and inducible nitric oxide mRNA in the maternal tissue. After receiving proper priming (IFNgamma) and triggering signal (lipopolysaccharide (LPS) or TNFalpha), decidual macrophages can secrete TNFalpha, nitric oxide (NO) and other cytotoxic molecules that could potentially damage placental cells and consequently compromise embryo survival. The objective of this study was to evaluate the cytotoxic effects of activated decidual macrophages on the fetoplacental unit. High and low loss murine mating models have been used to perform cytotoxicity assays. Our results show that: (1) decidual cells from the high loss model have a greater capacity to kill YAC-1 targets than those from the low loss model; (2) when decidual macrophages and NK cells are separated, both cells demonstrate cytotoxic activity by inducing lysis of the YAC-1 targets; (3) decidual macrophage-mediated killing of YAC-1 cells is not related to NO and TNFalpha production but is inhibited by the oxyradical scavenger N-acetyl-l-cysteine in a dose-dependent manner: (4) murine trophoblast cells are resistant to decidual cell-mediated lysis in vitro and inhibit decidual cell-mediated lysis of YAC-1 targets. Taken together, these results confirm that decidual macrophages and NK cells could be cytotoxic effectors at the maternal/fetal interface, demonstrate that trophoblasts are properly adapted to resist decidual cell-mediated lysis, and suggest that certain reactive oxygen intermediate, might damage cells other than trophoblasts around the fetoplacental unit.