Variation in composition of the intervillous space lining in term placentas of mothers with pre-eclampsia.

OBJECTIVE(S): To define composition of chorionic plate and test effects of pre-eclampsia on basal plate composition. STUDY DESIGN: Retrospective cohort study where distinct area fractions were measured in: healthy term chorionic plate (CP: n = 11), healthy placental basal plate (n = 11), mild pre-eclamptic basal plate (n = 10) and severe pre-eclamptic basal plate (n = 11). RESULTS: CP lining is partly endothelial. Mean anchoring villus (AV)/acellular (NS) basal plate area ratio decreased in pre-eclampsia (p = 0.048). There was a decreasing trend with increasing disease severity. Basal plate endothelial cell proportion was not significantly lower in severe pre-eclampsia than in healthy or mild pre-eclamptics. CONCLUSION(S): An inverse relationship between the proportions of fibrin and anchoring villi indicates that increased basal plate fibrin deposition and reduced basal plate materno-fetal anchoring area are part of pre-eclamptic disease progression. Endothelium lining intervillous surfaces may originate from circulating maternal endothelial progenitor cells.

Immunofluorescence confocal laser scanning microscopy and immuno-electron microscopic identification of keratins in human materno-foetal interaction zone.

We show here that at least 5 keratin proteins are present in villous trophoblast and the same 5 in extravillous trophoblast. A further 14 tested were undetectable in these tissues. In contrast, 10 of the 19 keratins tested were present in amniotic epithelium. The marking of amniotic epithelium on the one hand, as distinct from villous and extravillous trophoblast on the other, can be achieved using 5 keratins (K4, 6, 13, 14 and 17) with a mixture of positive and negative discrimination that is expected, in combination, to be highly sensitive. All the specific keratins identified in trophoblast were apparently up-regulated on the pathway to extravillous trophoblast. Co-ordinated differentiation at the molecular expression level is indicated by this finding. The relevant keratins are K5, 7, 8, 18 and 19. Specific keratins have been identified that are down-regulated in villous trophoblast in pre-eclamptic pregnancy. This difference between healthy and pre-eclamptic chorionic villous trophoblast keratin expression was statistically significant in 4 out of the 5 keratins. This was not the case for the extravillous trophoblast at the immunofluorescence confocal level but significant differences were obtained using immunogold electron microscopy. We suggest that the villous trophoblast in pre-eclamptic placentae is cytoskeletally weaker with respect to the filaments made from these specific proteins and that this is one reason why, in pre-eclampsia, trophoblast is deported in greater quantity than in healthy placentae.

Referral and attendance at a specialist antenatal clinic: qualitative study of women's views.

OBJECTIVE: To explore women's views on being referred to and attending a specialist antenatal hypertension clinic. DESIGN: Qualitative interview study. SETTING: A pregnancy hypertension clinic in a large teaching hospital in the East Midlands. POPULATION: Twenty-one women (aged 18 years and above) attending the pregnancy hypertension clinic for the first time during their current pregnancy. METHODS: Women who had been referred to and attended a specialist antenatal clinic participated in semi-structured interviews. Data analysis was based on the constant comparative method. MAIN OUTCOME MEASURES: Women's experiences and perceptions of being referred to and attending a specialist antenatal clinic. RESULTS: Being referred to the clinic conferred an 'at risk' status on women. Some women welcomed the referral but others experienced it as unsettling. Many were unclear about why they had been identified as being at risk or had difficulties in accepting the legitimacy of the reason for referral. Women were often inadequately informed about why they were referred to the clinic, what they could expect and the benefits of attending the clinic over management in the community. Although attendance at the clinic was cited as a source of reassurance, the reassurance was often made necessary by concern raised by the initial referral. CONCLUSIONS: Women's accounts suggest that the interface between community and secondary antenatal services needs improvement to minimise possible adverse effects from identifying women as being 'at risk' during pregnancy.

Activity patterns and time allocation during pregnancy: a longitudinal study of British women.

OBJECTIVE: Few studies provide data regarding the integrated everyday activities of Western pregnant women. The study aimed to quantify changes in the daily activity of women during pregnancy and to examine whether pregnancy has a differential impact on different activity domains. DESIGN: A prospective, longitudinal study of maternal time allocation and activity was carried out. METHODS: The time allocation patterns of 57 healthy nulliparous pregnant women were assessed at 16, 25, 34 and 38 weeks gestation by semi-structured interview. Mean total daily activity levels (DALs) were estimated according to the intensity and duration of each activity reported. Self-reported activity was sub-divided into occupational, recreational, domestic and nocturnal activity ratios. RESULTS: From 16 to 34 weeks gestation mean self-reported DAL declined significantly from 1.54 to 1.40 METS (Metabolic Equivalent TEE Score, where TEE is total energy expenditure) (p < 0.001). In the different activity domains, mean occupational activity ratio decreased (p < 0.002) whilst nocturnal activity ratio increased (p < 0.002) from 16 to 34 weeks. Mean recreational activity ratio decreased significantly between 25 and 38 weeks (p < 0.001) but no significant changes were observed in mean domestic activity ratio. CONCLUSIONS: Low-risk pregnancy has a differential impact on occupational, recreational and domestic domains. Economies in energy expenditure appear to be made in occupational and recreational activity while domestic activities are largely maintained during pregnancy. Changes in physical activity may be influenced more by the type of activity rather than the intensity of activity.

Confocal laser scanning microscope study of cytokeratin immunofluorescence differences between villous and extravillous trophoblast: cytokeratin downregulation in pre-eclampsia.

Pre-eclampsia is a disease characterized by failures in interstitial implantation. One product of the implantation process is the basal plate; a structure whose complexity makes it hard to fully appreciate the pathological changes in significant diseases of pregnancy. This article describes our use of CLSM immunofluorescence to examine the cytokeratin composition of the cells of trophoblastic origin in the term placental basal plate. Large differences in the content of the structural polymeric protein were compared using analysis of digital images. We show that greater pancytokeratin immunofluorescence is observed in extravillous cytotrophoblast cells as compared with villous trophoblast. There is a >30-fold difference in the mean area percent of the most intensely immunofluorescent pixels in the tissue containing these cells. This is a very high, statistically significant difference as defined by the Wilcoxon Signed Ranks Test Asym. Sig. (two-tailed): P < 0.001. The most invasive population of cells of the trophoblast lineage (the extravillous trophoblast) exhibits a significant reduction in cytokeratin immunofluorescence when comparisons of healthy and pre-eclamptic pregnancies are made. This ratio was 2.4:1. It was tested using the Mann-Whitney U-test. From healthy to pre-eclamptic the reduction was from mean rank 83.42((healthy)) to 51.13((pre-eclamptic)). The difference was very highly statistically significant (n = 53 + 75 = 128; U = 984.500; Z = -4.852; P < 0.001). There was also less cytokeratin-related immunofluorescence in villous trophoblast when healthy villi were compared with pre-eclamptic villi. The observed alterations in trophoblastic cytoskeletal components are expected to damage the anchorage and motility of cells. The extravillous trophoblast is known to be necessary for implantation. This leads to a cellular hypothesis of the failure of implantation resulting in reduced depth of uterine invasion and failure to adapt the spiral arterioles for low-pressure perfusion of the intervillus space, two well-known features of pre-eclampsia. The reduction in cytokeratin-related immunofluorescence in the villus trophoblast seen on comparing healthy term placentae with those from pre-eclamptics implies that the trophoblast is a weaker epithelial layer in the hypertensive pregnancy. This could account for the rise in deported trophoblast associated with pre-eclampsia. Deported trophoblast has been invoked as the systemic messenger that leads to generalized maternal hypertension seen in this condition.

Healthy and pre-eclamptic placental basal plate lining cells: quantitative comparisons based on confocal laser scanning microscopy.

Immunocytochemical confocal laser scanning microscope images of the monolayer of cells lining the intervillus space at the basal plate of term placentae were analysed using stereology. Immunoreactively-distinct regions of this mosaic layer were measured. In basal plate from healthy pregnancies, trophoblast epithelium occupied 18.91% of the surface area and endothelium 60.81%. In pre-eclampsia the equivalent areas were 15.57% and 67.63%. Acellular fibrinoid covers the remaining area and this component decreases in area in pre-eclampsia. The statistically significant increase in the cellular endothelial compartment may be relevant to the hypertensive pathology of pre-eclampsia as endothelial signalling plays a major role in regulation of blood pressure.

Home monitoring of blood pressure in pregnancy at high risk of pre-eclampsia.

The early detection of pre-eclampsia is a major challenge in obstetric care. We report a case where pre-eclampsia was detected by home blood pressure monitoring between routine antenatal visits. This novel management approach allows early diagnosis and optimises antenatal care in fulminating disease.

Plasma P-selectin is elevated in the first trimester in women who subsequently develop pre-eclampsia.

OBJECTIVE: To report plasma concentrations of the adhesion cell molecule P-selectin during pregnancy to determine the effect of subsequent development of hypertension and pre-eclampsia. DESIGN: A longitudinal study. METHODS: A longitudinal study involving 70 women followed up from early pregnancy; 20 who subsequently developed pre-eclampsia were compared with 24 who developed gestational hypertension and 26 normotensive women with normal obstetric outcome. The determination of citrate plasma soluble P-selectin levels throughout pregnancy was performed using a commercial quantitative sandwich immunoassay kit. The temporal course of plasma P-selectin in the three groups of subjects was analysed. RESULTS: There was no significant difference in mean plasma P-selectin concentration between normotensive and gestational hypertensive subjects at any stage of pregnancy. Using a cutoff level of 60 ng/mL, P-selectin concentration at 10-14 weeks had a negative predictive value for pre-eclampsia of almost 99%. Mean plasma P-selectin concentrations were significantly elevated by 10-14 weeks in women who later developed pre-eclampsia (P < 0.001). CONCLUSIONS: Our data support an inflammatory model for pre-eclampsia whereby endothelial cell activation may be secondary to a primary inflammatory response. Plasma P-selectin has significant potential as a first trimester clinical marker of pre-eclampsia.

Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance.

OBJECTIVE: The aim of this study was to measure maternal plasma vascular endothelial growth factor concentrations during normal and hypertensive pregnancies and examine their relationship with maternal total peripheral resistance values. STUDY DESIGN: Plasma concentrations of total immunoreactive vascular endothelial growth factor and total peripheral resistances were measured serially throughout pregnancy in 20 women with preeclampsia, 24 women with gestational hypertension, and 26 normotensive control women. One-way analysis of variance and a regression model were used to analyze the vascular endothelial growth factor levels in the groups and the relationship between vascular endothelial growth factor concentration and total peripheral resistance. RESULTS: At 10 to 14 weeks' gestation plasma vascular endothelial growth factor concentrations in all subjects were 4 to 5 times greater than the levels measured post partum (P <.0001). Mean vascular endothelial growth factor concentrations were similar in the control and gestational hypertension groups; in both groups levels remained stable until 34 to 36 weeks' gestation, when levels increased a further 1.3-fold (P <.01). In comparison, vascular endothelial growth factor concentrations in subjects in the preeclampsia group were greater at 28 to 32 weeks' gestation (P =.002) and at 34 to 36 weeks' gestation (P <.001). Vascular endothelial growth factor concentrations were also increased during the 4 weeks that preceded the diagnosis of preeclampsia (P <.05). Vascular endothelial growth factor concentrations were associated with the elevated total peripheral resistance observed during the clinical disorder in the preeclampsia group but not in the other groups. CONCLUSION: Maternal plasma vascular endothelial growth factor concentrations increased before the clinical onset of preeclampsia and were further elevated during the vasoconstricted state observed in this disorder. We speculate that the hyperdynamic circulation that characterizes the latent phase of preeclampsia causes vascular shear stress, which in turn increases the levels of circulating vascular endothelial growth factor. Because vascular endothelial growth factor normally acts as a vasodilator, its increase may represent an unsuccessful vascular rescue response.

Inpatient monitoring on an outpatient basis: managing hypertensive pregnancies in the community using automated technologies.

Automated measurement of blood pressure and urinalysis is reviewed, and the strengths and weaknesses of these devices are compared with conventional techniques. The few early reports of such management strategies are reviewed with emphasis on the advantages of automated monitoring. The article concludes with a review of published pilot data in this field and places those findings in the context of recent recommendations for the development of obstetric care in the United Kingdom.

[Photography methods in general and esthetic surgery: clinical significance and impact on surgical performance]. / Fotografia estemporanea in chirurgia generale ed estetica. Significato clinico ed impatto sulla performance chirurgica.

The authors outline and emphasize the use of Polaroid technique in the surgical practice, either in emergency room (pre-, intra- and postoperative photography) or in plastic-reconstructive surgery, where informed consent is needed on the basis of surgical plan. Polaroid photos are suitable to be enclosed in the patient record as well as in the legal documentation. The Polaroid Macro-5SLR camera is specifically useful in the medical practice to improve the doctor-patient relationship.

Maternal central hemodynamics in hypertensive disorders of pregnancy.

OBJECTIVE: To document maternal central hemodynamics during the preclinical and clinical phases of nonproteinuric gestational hypertension and preeclampsia. METHODS: We conducted a longitudinal study of 400 primigravidas who were monitored throughout pregnancy using Doppler echocardiography. Multinomial logistic regression was used to identify variables associated with risk of hypertension. RESULTS: Gestational hypertension developed in 24 women and preeclampsia developed in 20. Compared with normotensive controls, women who had preeclampsia had significantly elevated cardiac outputs before clinical diagnosis, but total peripheral resistance was not significantly different during this latent phase. During the clinical phase of preeclampsia, there was a marked reduction in cardiac output and increase in peripheral resistance. All women who had gestational hypertension had significantly elevated cardiac outputs before and during the clinical course of the condition. CONCLUSION: Our data support the concept of a hyperdynamic disease model for preeclampsia, with a subsequent hemodynamic crossover to low cardiac output and high resistance circulation coinciding with the onset of the clinical syndrome. Women with gestational hypertension had no such hemodynamic crossover and maintained hyperdynamic circulation throughout pregnancy.

[Ultrasonic imaging of coronary atherosclerosis]. / Imagerie ultrasonore de l'athérosclérose coronaire.

Intra-coronary ultrasonography (ICV) is a technique for in vivo study of the different layers of the arterial wall, the site of atherosclerosis. A qualitative analysis of the composition of the plaque can predict its potential evolutivity (chronic with slow progression or at risk of rupture and causing acute thrombosis) and its response to different types of angioplasty, which could eventually become and essential factor in the choice of appropriate therapeutic strategy. Analysis of the results of B mode ultrasonic scanning has provided correlations with the histological composition of the arterial wall, validating the method and opening up the field of tissue characterisation which hitherto had been limited by the absence of sufficiently reliable, accurate and reproducible quantitative parameters. Magnetic resonance imaging (MRI) is a complementary, non-invasive tool for tissue analysis because its sensitivity to the biophysical and biochemical properties of tissues which makes it a promising method of morphological and functional imaging. Other methods of imaging atheromatous plaques include angioscopy and optic coherence tomography which have also contributed to the improvement in our knowledge of atherosclerosis. These methods of imaging which are slowly overcoming their limitations provide documents which ressemble more and more the histological appearances. Intracoronary ultrasonography is the most promising method and raises hopes that one day we shall be able to predict the outcome and anticipate the risk of rupture of atherosclerotic plaques.