RESUMEN
OBJECTIVE: To compare the experience and attitude of obstetricians in Europe towards late termination of pregnancy and the factors affecting their responses. DESIGN: Cluster sampling cross-sectional survey. All neonatal intensive care unit (NICU)-associated maternity units were recruited (census sampling) in Luxembourg, the Netherlands and Sweden. In France, Germany, Italy, Spain and the UK, units were selected at random. In every recruited unit, all obstetricians with at least 6 months' experience were invited to participate. SETTING: NICU-associated maternity units in eight European countries. POPULATION: Obstetricians with at least 6 months' clinical experience. METHODS: An anonymous, self-administered questionnaire was used. Multinomial logistic analysis was used to identify factors predicting the obstetricians' views about modifying the law governing late termination in their country. MAIN OUTCOME MEASURE: Obstetricians' experience of late termination of pregnancy and views about national policies. RESULTS: One hundred and five units and 1530 obstetricians participated (response rates 70 and 77% respectively). The most common indications for late termination were congenital anomalies and women's physical health. Feticide was not common except in France, Luxembourg and the UK. Active euthanasia of a liveborn was practiced in France and the Netherlands. Obstetricians in Germany were more likely to feel that late termination should be more severely restricted, the opposite was true in Spain and the Netherlands. In Italy, there was dissatisfaction with current status, but opinion was divided, reflecting views on both sides of the debate. CONCLUSIONS: This research outlines current practice in a difficult and sensitive area and suggests the need for more discussion and support for all those who were involved.
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Actitud del Personal de Salud , Actitud Frente a la Salud , Trabajo de Parto Inducido/legislación & jurisprudencia , Obstetricia , Aborto Terapéutico/legislación & jurisprudencia , Aborto Terapéutico/psicología , Adulto , Análisis por Conglomerados , Consejo , Estudios Transversales , Europa (Continente) , Femenino , Política de Salud , Humanos , Trabajo de Parto Inducido/psicología , Persona de Mediana Edad , Embarazo , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To explore the attitudes of obstetricians to perform a caesarean section on maternal request in the absence of medical indication. DESIGN: Cluster sampling cross-sectional survey. SETTING: Neonatal Intensive Care Unit (NICU) associated maternity units in eight European countries. POPULATION: Obstetricians with at least 6 months clinical experience. METHODS: NICU-associated maternity units were chosen by census in Luxembourg, Netherlands and Sweden and by geographically stratified random sampling in France, Germany, Italy, Spain and UK. An anonymous, self-administered questionnaire was used for data collection. MAIN OUTCOME MEASURES: Obstetricians' willingness to perform a caesarean section on maternal request. RESULTS: One hundred and five units and 1,530 obstetricians participated in the study (response rates of 70 and 77%, respectively). Compliance with a hypothetical woman's request for elective caesarean section simply because it was 'her choice' was lowest in Spain (15%), France (19%) and Netherlands (22%); highest in Germany (75%) and UK (79%) and intermediate in the remaining countries. Using weighted multivariate logistic regression, country of practice (P<0.001), fear of litigation (P= 0.004) and working in a university-affiliated hospital (P= 0.001) were associated with physicians' likelihood to agree to patient's request. The subset of female doctors with children was less likely to agree (OR 0.29, 95% CI 0.20-0.42). CONCLUSIONS: The differences in obstetricians' attitudes are not founded on concrete medical evidence. Cultural factors, legal liability and variables linked to the specific perinatal care organisation of the various countries play a role. Greater emphasis should be placed on understanding the motivation, values and fears underlying a woman's request for elective caesarean delivery.
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Actitud del Personal de Salud , Actitud Frente a la Salud , Cesárea/psicología , Procedimientos Quirúrgicos Electivos/psicología , Obstetricia , Adulto , Estudios Transversales , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Defensa del Paciente , EmbarazoRESUMEN
OBJECTIVE: Soluble vascular cell adhesion molecule-1 (VCAM-1) is known to be elevated in serum of patients with preeclampsia, but there are no data available on the significance of urinary VCAM-1 excretion in preeclampsia. The aim of our study was to uncover possible circadian rhythms of VCAM-1 plasma levels and urinary VCAM-1 excretion in uncomplicated and hypertensive pregnancies and to ascertain their relation to blood pressure. STUDY DESIGN: A total of 10 normotensive and 10 preeclamptic pregnant women were included in this study. Venous blood was collected hourly, and urine samples were taken every 2 h over a period of 24 h. VCAM-1 levels were determined by ELISA. We compared these results with the circadian blood pressure rhythm. RESULTS: The median VCAM-1 plasma levels were significantly (P < 0.01) increased in preeclamptic patients (851.5 ng/mL) in comparison to normotensive pregnant women (659.3 ng/mL) without any circadian rhythm being apparent; however, the urinary excretion of VCAM-1 showed a typical circadian rhythm, with a higher excretion rate during daytime. CONCLUSION: For the first time we have demonstrated that urinary VCAM-1 excretion in pregnancy shows a circadian rhythm without correlation to plasma levels or the circadian blood pressure rhythm. In contrast, VCAM-1 serum levels did not show a diurnal rhythm. We assume that VCAM-1 serum levels do not correlate with systemic blood pressure or urinary excretion.
Asunto(s)
Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Preeclampsia/fisiopatología , Molécula 1 de Adhesión Celular Vascular/sangre , Molécula 1 de Adhesión Celular Vascular/orina , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Preeclampsia/sangre , Preeclampsia/orina , Embarazo , Valores de Referencia , SolubilidadRESUMEN
Impaired invasion of uteroplacental arteries by extravillous trophoblast cells is a key pathogenic mechanism of preeclampsia. We previously demonstrated that reduced trophoblast invasion into uteroplacental spiral arteries was associated with an excess of macrophages in and around these arteries. To explore the significance of these observations, we correlated the extent of extravillous trophoblast apoptosis in placental bed biopsy specimens with macrophage distribution and studied the effect of macrophages upon trophoblast apoptosis in vitro. Extravillous trophoblast hybrid cells were cocultured with activated macrophages exposed to exogenous tumor necrosis factor alpha (TNFalpha), anti-tumor necrosis factor receptor I (TNF-RI), and tryptophan depletion, and the rates of trophoblast apoptosis were measured. Extravillous trophoblast hybrid cells showed increased rates of apoptosis following exposure to exogenous TNFalpha, with tryptophan depletion, and when cocultured with activated macrophages. The proapoptotic effects of macrophages in vitro were completely inhibited only by simultaneous addition of tryptophan and anti-TNF-RI. Our data indicate that macrophages, residing in excess in the placental bed of preeclamptic women, are able to limit extravillous trophoblast invasion of spiral arterial segments through apoptosis mediated by the combination of TNFalpha secretion and tryptophan depletion. The mechanisms by which macrophages are activated and recruited to the placental bed are presently unknown but are likely central to the pathogenesis of preeclampsia.
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Apoptosis , Macrófagos/fisiología , Preeclampsia/etiología , Preeclampsia/patología , Trofoblastos/patología , Útero/patología , Adulto , Antígenos CD , Arterias/patología , Biopsia , Endotelio Vascular/patología , Femenino , Humanos , Células Híbridas , Inmunohistoquímica , Modelos Biológicos , Placenta/irrigación sanguínea , Embarazo , Receptores del Factor de Necrosis Tumoral/antagonistas & inhibidores , Receptores Tipo I de Factores de Necrosis Tumoral , Trofoblastos/metabolismo , Triptófano/metabolismo , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
INTRODUCTION: The antiphospholipid antibody syndrome (APA) is a potentially life-threatening disease in pregnancy, associated with spontaneous abortion, intrauterine growth retardation (IUGR), preeclampsia and foetal death in utero. One of the sequelae of the antiphospholipid-antibodies is an impaired uteroplacental circulation. We present a case where we diagnosed an antiphospholipid antibody syndrome (APA) on the basis of a highly pathological Doppler flow in both uterine arteries. CASE REPORT: A 35-year-old G2P0 with a history of intrauterine foetal death in the 24th week was seen at 15 weeks in her second pregnancy for an ultrasound scan. The Doppler study of both uterine arteries showed highly pathological resistance indices and bilateral notching. Laboratory studies revealed elevated levels of antibodies against Cardiolipin and phospholipids. Therapy trials with low-dose aspirin, heparin, corticosteroids, hemodilution therapy and immunoglobulin remained unsuccessful. The foetus developed severe IUGR, anhydramnios and foetal distress. In the 26th week the parents insisted on a caesarean section because of a pathological heart rate pattern. The birth weight was 365 grams and the infant died immediately. DISCUSSION: There are several mechanisms which impair the uteroplacental circulation in an APA syndrome. Therefore it is essential to perform laboratory tests when detecting a pathological blood flow in both uterine arteries. In this case all therapies failed, and the preterm infant died due to severe IUGR and distress. The diagnosis, however, facilitated the introduction of early anticoagulation therapy for the mother, the exclusion of systemic lupus erythematodes and the counselling of the parents with regard to further pregnancies.
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Síndrome Antifosfolípido/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico por imagen , Isquemia/diagnóstico por imagen , Placenta/irrigación sanguínea , Complicaciones del Embarazo/diagnóstico por imagen , Ultrasonografía Prenatal , Útero/irrigación sanguínea , Femenino , Muerte Fetal , Humanos , Recién Nacido , Embarazo , Ultrasonografía Doppler , Resistencia Vascular/fisiologíaRESUMEN
In developed western countries endometrial cancer is the most common malignant tumor of the female genital tract. 75% of cases are diagnosed in stage I where cure rates of 75-90% are achieved. In stage II, 5-year survival rates amount only to 50%, in stage III up to 30%, and in stage IV to less than 10%. Despite the preponderance of early stage endometrial cancer, about 20-30% of affected patients will die from this disease. As surgical treatment and/or irradiation are not able to control advanced disease, many investigators have been searching for systemic treatment modalities. Cytotoxic chemotherapy achieves high initial response rates of about 40-60%. Recurrence, however, occurs after a median duration of only a few months. As endometrial cancer develops from hormone dependent cells, endocrine treatment has been the traditional palliative therapy of advanced tumor stages. Several studies to date have failed to demonstrate an efficacy of adjuvant hormonal therapy in cases of high-risk endometrial cancer. For the conservative treatment of precancerous, non-invasive hyperplastic lesions of the endometrium, endocrine therapies have been shown to be efficacious.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Femenino , Humanos , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Cuidados PaliativosRESUMEN
PURPOSE: Lethal osteochondrodysplasias show an abnormal maturation and a disturbed growth of cartilage and bones. They represent a heterogeneous group of rare genetic diseases. Their incidence is 1 to 3 in 10,000 births. MATERIAL AND METHODS: We report altogether 5 cases: two of thanatophoric dysplasia, one of achondrogenesis type II and two cases of the rare fibrochondrogenesis. The differential diagnosis in respect to ultrasonographic, morphologic, radiographic and histopathologic criteria of the most common of these diseases are discussed together with a review of the literature. RESULTS: On the basis of the ultrasound finding of the short-rib-syndrome, it is possible to differentiate between viable and lethal osteochondrodysplasias at 19 to 22 weeks of gestation. The short-rin-syndrome leads to pulmonary hypoplasia. CONCLUSIONS: It is essential to obtain an exact diagnosis postnatally by radiographic and histopathological examinations to counsel the parents concerning the risk of recurrency. The risk in this heterogeneous group of genetic diseases ranges between less than 1% up to 50% depending on the final diagnosis. Our two cases of fibrochondrogenesis in a consanguineous couple strongly suggest an autosomal recessive inheritance in this disease.
Asunto(s)
Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/embriología , Ultrasonografía Prenatal , Adulto , Femenino , Muerte Fetal , Edad Gestacional , Humanos , Recién Nacido , Masculino , Osteocondrodisplasias/clasificación , Osteocondrodisplasias/patología , EmbarazoRESUMEN
OBJECTIVE: We evaluated the role of clinical non-overt stage III diabetic nephropathy concerning the development of more frequent hypertensive complications during pregnancies of women requiring insulin. METHODS: 122 unselected pregnant women treated with insulin were enrolled in the study, of whom 56 were type-1 diabetic patients and 66 patients had gestational diabetes. In 24-h urine samples, excretion rates of albumin (UAE) and beta(2)-microglobulin were determined by nephelometric analysis and a radioimmunoassay, respectively. These parameters were also measured in the serum as well as HbA(1c), fructosamine and daily blood glucose profiles. RESULTS: Sixteen (15.7%) women had an elevated UAE (>30 mg/24 h), of whom three had macroalbuminuria (UAE>300 mg/24 h). Thirteen (12.7%) insulin-treated women showed microalbuminuria during pregnancy, eight with type-1 diabetes and five with gestational diabetes requiring insulin. In the entire group hypertension was observed in seven (6.9%) women of whom six had microalbuminuria. The sensitivity and specificity were 85.7% and 92.6%, respectively. The positive predictive value reached 46.2%, whereas the negative predictive value was 98.9%. CONCLUSION: Measurement of UAE in diabetic pregnancies seems to be an useful additional parameter for risk evaluation of hypertensive disorders.
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Albuminuria/orina , Nefropatías Diabéticas/complicaciones , Hipertensión/etiología , Insulina/uso terapéutico , Complicaciones Cardiovasculares del Embarazo/etiología , Embarazo en Diabéticas/complicaciones , Adolescente , Adulto , Glucemia/análisis , Nefropatías Diabéticas/orina , Femenino , Fructosamina/sangre , Hemoglobina Glucada/análisis , Humanos , Embarazo , Embarazo en Diabéticas/tratamiento farmacológico , Factores de RiesgoAsunto(s)
Muerte Fetal/epidemiología , Síndrome HELLP/mortalidad , Síndrome HELLP/terapia , Complicaciones Hematológicas del Embarazo/mortalidad , Complicaciones Hematológicas del Embarazo/terapia , Resultado del Embarazo , Estudios de Evaluación como Asunto , Femenino , Edad Gestacional , Síndrome HELLP/diagnóstico , Humanos , Cooperación Internacional , Mortalidad Materna/tendencias , Embarazo , Complicaciones Hematológicas del Embarazo/diagnóstico , PronósticoRESUMEN
Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.
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Neoplasias Endometriales/metabolismo , Estrógenos/metabolismo , Neoplasias Hormono-Dependientes/metabolismo , Anticonceptivos Hormonales Orales/metabolismo , Neoplasias Endometriales/etiología , Antagonistas de Estrógenos/metabolismo , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Factores de Riesgo , Tamoxifeno/metabolismoRESUMEN
OBJECTIVE: To examine whether prostate-specific antigen (PSA) is present in amniotic fluid, whether the amniotic fluid PSA concentration changes with gestational age, and whether there is an association between amniotic fluid PSA and fetal sex. METHODS: The PSA concentration was measured in the amniotic fluid of 48 pregnant women. Thirty-four samples were obtained during routine amniotic fluid analyses performed during gestational weeks 16-18, whereas 14 samples were obtained during cesarean section performed after gestational week 36. RESULTS: PSA was detected in all amniotic fluid samples. The median amniotic fluid PSA was 0.193 ng/ml during gestational weeks 16-18 and 0.39 ng/ml after gestational week 36 (p = 0.1). Furthermore, no significant association was seen between amniotic fluid PSA and fetal sex. The median amniotic fluid PSA level was 0.233 ng/ml for the 21 boys and 0.222 ng/ml for the 27 girls investigated (p = 0.72). CONCLUSIONS: These results confirm recent literature reports that PSA may serve as a growth regulator during normal fetal development. However, further studies are necessary to elucidate the exact role of PSA during fetal development.
Asunto(s)
Líquido Amniótico/química , Antígeno Prostático Específico/análisis , Cesárea , Desarrollo Embrionario y Fetal , Femenino , Edad Gestacional , Humanos , Técnicas para Inmunoenzimas , Masculino , Embarazo , Antígeno Prostático Específico/fisiología , Factores SexualesRESUMEN
We report on a patient with an eight-year history on maintenance hemodialysis treatment without residual renal function in whom pregnancy was successfully managed through to the 29th week. During this time, under carefully modified dialysis treatment, the nephrologic course, as well as materno-fetal flow relationships were unremarkable. Fetal development was appropriate for gestational age. However, pregnancy was complicated by polyhydramnios, which necessitated i.v. tocolysis. In the 28 + 6th week of gestation, cesarean section was performed because of an antibiotic-resistant fever of unclear origin which ceased within two days of delivery. Although the postnatal course of the adequately developed baby was complicated by the respiratory distress syndrome, normal development continued. We emphasize that the intensive interdisciplinary cooperation of nephrologists and obstetricians is imperative for the successful management of pregnancy under these conditions. In these pregnancies, the main fetal problems consist of premature labor because of polyhydramnios, preterm delivery, intrauterine growth retardation and stillbirth. The mother is threatened by the development of superimposed pre-eclampsia, left ventricular failure because of volume overload and progressive anemia. In order to maintain a well-balanced homeostasis, intensification of dialysis therapy by an increase in frequency and duration is the most important therapeutic approach. Accurate fetal monitoring including frequent examination of the feto-maternal circulation by Doppler sonography as well as attentive surveillance of the mother is required to recognize the above mentioned complications.
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Fallo Renal Crónico/terapia , Polihidramnios/etiología , Diálisis Renal , Adulto , Cesárea , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Fallo Renal Crónico/complicaciones , Masculino , Polihidramnios/diagnóstico , Polihidramnios/cirugía , Embarazo , Resultado del Embarazo , Tercer Trimestre del EmbarazoRESUMEN
OBJECTIVE: The purpose of the present study was to evaluate the clinical significance of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) for endothelial cell activation in pre-eclampsia. Therefore, we determined and compared the correlations between these cytokines and circulating adhesion molecules in the sera of pre-eclamptic pregnant women, normotensive pregnant women and nonpregnant women. METHODS: The soluble adhesion molecules VCAM-1, ICAM-1, E-selectin, and P-selectin were determined in the serum of 38 pre-eclamptic pregnant women and 40 normotensive pregnant and nonpregnant controls using ELISA-techniques. We correlated these serum concentrations with the serum levels of TNF-alpha and IL-1beta, respectively, also determined by ELISA. RESULTS: Elevated serum levels of VCAM-1 and E-selectin could be detected in pre-eclamptic patients, with and without HELLP-syndrome. In contrast, no increased serum concentration of ICAM-1, P-selectin, TNF-alpha and IL-1beta were found in these patients. While significant correlation between VCAM-1 and E-selectin could be determined (r=0.604; p<0.001) no unambiguous correlations, however, were found between TNF-alpha or between IL-1beta and the examined adhesion molecules or the selectins. CONCLUSIONS: In contrast to in vitro investigations on cultured umbilical vein endothelium, our experimental results indicate that the cytokines TNF-alpha and IL-1beta can not explain endothelial cell activation, and that their measurement in serum is not useful for the detection of pre-eclampsia.
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Moléculas de Adhesión Celular/sangre , Endotelio Vascular/fisiopatología , Interleucina-1/fisiología , Preeclampsia/sangre , Factor de Necrosis Tumoral alfa/fisiología , Adulto , Selectina E/sangre , Femenino , Síndrome HELLP/sangre , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-1/análisis , Selectina-P/sangre , Embarazo , Factor de Necrosis Tumoral alfa/análisis , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
BACKGROUND: Prostate-specific antigen (PSA) is found in 30-40% of female breast tumors, as recently described. Diamandis and co-workers could demonstrate that PSA correlate significantly to a relapse-free survival and lower tumor stages in patients with breast cancer using a time-resolved immunofluorometric analysis. The presence of PSA in these tumors seems to reflect a favourable prognostic marker for that disease. The aim of our study was to evaluate the role of PSA as a prognostic factor in breast cancer using an immunohistochemical technique. MATERIALS AND METHODS: The PSA immunoreactivity of tissues from one-hundred women with malignant breast tumors was correlated to tumor staging, histomorphological tumor type, and biochemical estrogen and progesterone receptor content. Additionally, survival analysis was performed according to Kaplan and Meier. RESULTS: 49% of the tumors revealed positive staining for PSA. No significant correlation between PSA and the other parameters, or the mean survival time (PSA pos.: 5.3 years, PSA neg.: 5.4 years) could be demonstrated. CONCLUSIONS: As there were no significant correlations between PSA and other prognostic markers, PSA detected by immunohistochemistry seems not to be helpful in prognostic evaluation of breast cancer.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Antígeno Prostático Específico/análisis , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Análisis de Supervivencia , Tasa de Supervivencia , Factores de TiempoRESUMEN
Placental bed biopsies taken during caesarean section from 10 patients with pre-eclampsia and six healthy pregnancies were studied. We applied antibodies against cytokeratin and different macrophage markers to analyse the distribution of invasive extravillous trophoblast cells as compared to that of macrophages in myometrial segments of uteroplacental arteries. The data were evaluated quantitatively. We found a clear inverse relationship between local infiltration with macrophages and trophoblast invasion. In pre-eclampsia, vessel cross-sections prevailed which were characterized by large numbers of macrophages but a low degree of trophoblast invasion. In contrast, in normal third trimester pregnancies the respective arterial segments had a high degree of trophoblast invasion but were largely void of macrophages. These data suggest causal links between macrophages and inhibition of intra-arterial trophoblast invasion in pre-eclampsia.
Asunto(s)
Arterias/patología , Macrófagos/patología , Placenta/irrigación sanguínea , Preeclampsia/patología , Adulto , Biopsia , Recuento de Células , Femenino , Humanos , Queratinas/análisis , Embarazo , Trofoblastos/química , Trofoblastos/patologíaRESUMEN
OBJECTIVE: Adhesion molecules, such as vascular cell adhesion molecule 1, are known to be increased in the serum of patients with preeclampsia, indicating that these molecules are possible markers of endothelial cell activation. We investigated the influence of serum from women with preeclampsia on the expression of adhesion molecules by cultured endothelial cells. STUDY DESIGN: Human umbilical vein endothelial cells were cultured in Ham/Iscove modified Dulbecco's medium containing 20% pooled human serum, l -glutamine (200 mmol/L), penicillin, and streptomycin. We stimulated these cells for 24 hours with sera from patients with preeclampsia and then determined the levels of vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, E-selectin, and P-selectin in the supernatant and in the maternal serum by means of enzyme-linked immunosorbent assay. These results were compared with those of sera obtained from normotensive pregnant and nonpregnant women. In addition, the expressions of these adhesion molecules on the endothelial surface were determined by immunofluo-rescence microscopy. RESULTS: Only for vascular cell adhesion molecule 1 and E-selectin were elevated plasma levels found in hypertensive patients, whereas intercellular cell adhesion molecule 1 and P-selectin showed similar plasma levels in all the patients. No differences in the levels of the adhesion molecules were found between the supernatants of endothelial cell cultures after stimulation with sera from patients with preeclampsia and those after stimulation with normotensive control sera. In contrast, with immunofluorescence microscopy we could detect higher amounts of vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, and E-selectin on the endothelial surface after stimulation with sera from women with preeclampsia. CONCLUSION: Although vascular cell adhesion molecule 1 and E-selectin were elevated in maternal serum samples from women with preeclampsia and on the endothelial surface after stimulation with such sera, there were no detectable increases in the levels of both of these adhesion molecules in the supernatant of cultured endothelial cells. We therefore assume that sera from women with preeclampsia may cause endothelial cell activation. Because we could not detect elevated concentrations of any of the investigated adhesion molecules in the supernatant of endothelial cells, we believe that factors other than sera from women with preeclampsia seem to play a major role in the release of soluble forms of adhesion molecules from the endothelial membrane.
Asunto(s)
Moléculas de Adhesión Celular/fisiología , Endotelio Vascular/fisiopatología , Preeclampsia/fisiopatología , Adulto , Fenómenos Fisiológicos Sanguíneos , Moléculas de Adhesión Celular/metabolismo , Membrana Celular/metabolismo , Células Cultivadas , Selectina E/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Preeclampsia/sangre , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , Solubilidad , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
There is considerable evidence that endothelial damage, followed by the release of vasoactive substances contributes to the pathophysiology of preeclampsia. Because of controversial experiences in literature we wanted to evaluate the potential cytotoxic effect of preeclamptic sera on cultured endothelial cells. Therefore cultured human umbilical vein endothelial cells (HUVEC) were stimulated with sera obtained from preeclamptic patients, while sera from normotensive pregnant and nonpregnant women served as controls. To prove the viability of these cells we performed ethidiumbromide/acridinorange immunostaining and determined t-PA/PAI-1 release into the supernatant. These experiments could not show any cytotoxic effect on endothelial cells. In ongoing studies we measured the concentrations of adhesion molecules, markers of endothelial activation, in maternal sera, in the supernatant of cultured endothelial cells, and on cell surface after stimulation with the above mentioned sera. In the supernatant we couldn't determine any different concentrations of adhesion molecules after stimulation with the different sera, but using immunofluorescence-microscopy an increased concentration of those molecules could be detected on the endothelial surface after stimulation with preeclamptic sera than compared to sera from normotensive controls. In conclusion, our experiments support the hypothesis that sera from preeclamptic women may cause endothelial activation.
Asunto(s)
Endotelio Vascular/fisiopatología , Preeclampsia/fisiopatología , Moléculas de Adhesión Celular/fisiología , Supervivencia Celular/fisiología , Células Cultivadas , Femenino , Humanos , Recién Nacido , Embarazo , Valores de ReferenciaRESUMEN
It is generally accepted that insufficient invasion of trophoblast cells into the myometrial portions of the spiral arteries is thought to play a crucial role in the development of preeclampsia. As a consequence, uteroplacental vessels fail to undergo adaptive changes which are imperative to provide a sufficient blood supply to the placenta. Consecutive placental hypoxia is supposed to cause secretion/shedding of still unidentified placental metabolites resulting in different forms of pregnancy-induced hypertension. This review presents published data concerning the causes of insufficient trophoblast invasion in preeclampsia. Expression of HLA-G by extravillous trophoblast cells seems to be altered, resulting in activation of the maternal immune system. The pattern of integrin expression as well as the secretion of proteases is reported to be disturbed, which could lead to a reduced invasive potential of the trophoblast cells. Recent data indicate a pathophysiological role of NK-cells and macrophages in the altered trophoblast invasion. Also angiotensinogen Thr235 polymorphism seems to alter early physiologic changes in spiral arteries. In summary, preeclampsia seems to be induced by a multifactorial disturbance of trophoblast invasiveness which is characterized by reduced invasiveness of the trophoblast cells themselves and by an activated maternal immune response blocking the invasion by the semiallogenic trophoblast.
Asunto(s)
Placentación/fisiología , Preeclampsia/fisiopatología , Trofoblastos/fisiología , Femenino , Humanos , Hipertensión/fisiopatología , Recién Nacido , Placenta/irrigación sanguínea , Embarazo , Flujo Sanguíneo Regional/fisiologíaRESUMEN
In the present study the flow profile of the umbilical vein between the 14th and 24th weeks of pregnancy was examined for the first time in connection with pathological pregnancies and chromosomal/fetal anomalies, and compared with the flow pattern of normal pregnancies. The aim of our study was to clarify whether at this early stage in gestation the diagnosis of the fetal condition should be extended to include the monitoring of the umbilical vein and to assess the possibility of making predictions about the further course of pregnancy. 50 pregnant patients without complications, 21 patients later developing pregnancy-induced hypertension/intrauterine growth retardation, 16 pregnancies with fetal anomalies, and 4 pregnancies with chromosomal aberrations were scanned with color Doppler sonography to determine the flow spectra of the umbilical vein in a free loop. Admission criteria were single-child pregnancies and precise knowledge of the duration of gestation. Pulsations of the venous blood flow, which are physiological during the first three months of pregnancy, cease in normal pregnancies from the beginning of the second trimester. In cases where pregnancy-induced hypertension/intrauterine growth retardation developed, 2 out of 21 patients showed pulsations. In the pregnancies in which fetal and/or chromosomal anomalies occurred, pulsations in the flow pattern of the umbilical vein were detected in 14 out of 20 cases. The pulsations of the venous blood flow, which are attributable to a late diastolic reflux component in the venous circulation, are common finding in fetal/chromosomal anomalies. In our opinion, the flow spectrum of the umbilical vein should therefore be incorporated in sonographic screenings, and if pulsations are detected, we advise careful sonographic abnormality diagnostics and an investigation of the karyotype.
Asunto(s)
Aberraciones Cromosómicas , Anomalías Congénitas/fisiopatología , Enfermedades Fetales/fisiopatología , Edad Gestacional , Flujo Pulsátil , Venas Umbilicales , Adolescente , Adulto , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Humanos , Hipertensión/fisiopatología , Embarazo , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Segundo Trimestre del EmbarazoRESUMEN
We report on Doppler sonographic findings of a dialysis patient with renal anemia during otherwise uncomplicated pregnancy. Uteroplacental and fetoplacental flow relationships before, as well as after the dialysis treatments during the course of the pregnancy were in the normal range. The favorable flow condition in the utero- and fetoplacental circulation was associated with a low hematocrit. This in accordance with previous reports indicates a more favorable maternal and fetal outcome in association with a low hematocrit/hemoglobin concentration.