[Thrombophilic risk factors and complications during pregnancy - Expectations and reality].
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Biomedical subjects
Publications and source records attributed to W Rath.
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AIM: Ongoing technical progress has increased the accuracy of imaging in ultrasound mammography. Using a 10-MHz-transducer, eight different criteria of dignity were evaluated for validity, also with regard to the size of a tumor. MATERIALS AND METHODS: Over a period of three years, 446 breast tumors were ultrasonographically examined by two experienced medical doctors. The study comprised only suspicious lesions detected by mammography and/or manual palpation. Diagnostic validity was quantified by means of sensitivity, specificity, positive and negative predictive value, as well as the ODDS-ratio. RESULTS: Ultrasound mammography demonstrated a sensitivity of 94.0 %, specificity of 91.4 %, positive predictive value of 95.9 %, and a negative predictive value of 99.1 %. Eight different sonographic criteria were validated separately. The most important signs of malignancy were (in descending order): a highly echogenic halo, spikes, jagged contour, posterior acoustic shadowing, and discontinuity of tissue structure. Features of benign disease were: smooth edge, posterior acoustic enhancement, displacement margin, bilateral acoustic shadowing and continuity of tissue structure. Furthermore, it appeared that the size of a tumor only had consequences on posterior shadowing (p = 0.017). All other features did not show significant variation in relation to tumor size. CONCLUSION: We were able to prove that ultrasound mammography is an excellent medium for the differentiation of benign and malignant breast lesions, when precise indication criteria were adhered to, even in cases of small tumor size.
Various strategems of complexity analysis of microvascular blood flow were carried out in several fields of medicine in the past, as such as angiology, ophthalmology and neurology. The introduction of colour-angio-mode, a special form of colour coded Doppler sonography, now makes possible to perform complexity analysis of the placental blood displacement even in the absence of information about hydrodynamic details such as directionality, velocity profile and number of displaced blood cells. Algorithms were developed which allows to extract information concerning the time averaged power of phonon-erythrocytes collision events (from the square of the frequencies of back scattered ultrasound recorded during 166 ms) in 20,000 to 40,000 regions of interest. The obtained values are being displayed as false coloured pixels on a video-screen, we succeeded to obtain quantitative data about displacement rates.In cross-sectional and longitudinal studies we generated typical diagrams displaying the "occurrence rate" of various powers of displacement over time. By this mode of display contour plots can be generated, showing a large amount of low intensity pixels and a small amount of high intensity pixels representing the parenchymatous blood flow inside the placenta. As was to be expected, interdependencies between the placental blood flow and the maternal and fetal heart rates as well as the maternal breathing can be found. While there was only limited influence of maternal and fetal heart rate on the placental blood flow, maternal breathing showed striking influence. Surprisingly, during expiration the power of placental blood movement was decreased, and there was a marked increase during inspiration. In cases of severe intrauterine growth retardation, colour pixel intensities were seen to transiently vanish during end-expiration. The power of placental blood displacement was marked increased subsequent to reducing maternal hematocrit during hemodilution therapy by infusion of artificial colloids. These interdependencies could be confirmed by ex vivo examinations perfusing and percolating the placenta after birth in a hemodynamic model. Additionally, we found interdependencies between fetal and maternal blood displacement inside the placenta. By modelling the decrease of fetal inotropic power in the ex vivo examinations, increase in the power of maternal blood displacement in the intervillous space. The two types of placental blood flow are known to be determined by many factors. While it is currently impossible to measure all these parameters determining an parenchymatous blood flow, it is possible to obtain useful informations about the physiologic and pathophysiologic changes of placental blood flow using colour-angio-mode as a tool of complexity analysis based on the distribution of local blood displacement. This new knowledge can help to understand clinically relevant changes in the individual patient as well their underlying causes.
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OBJECTIVE: The aim of the study was to investigate the role of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) in the diagnosis of recurrent ovarian cancer. METHODS: One hundred six FDG PET scans performed in 54 patients in the follow-up after cytoreductive surgery and chemotherapy of ovarian cancer were reevaluated. Fifty-eight scans were performed in patients with suspected recurrence and 48 scans in patients who were clinically disease free. Thirty-seven PET scans were validated by histology and 66 studies by a median follow-up of 22 months in disease-free patients or 12 months in patients with recurrent disease. Three scans were validated by concordant positive findings of tumor marker CA125, computed tomography, and FDG PET. RESULTS: FDG PET correctly identified recurrent disease in 73/88 cases. PET ruled out recurrent disease in 15/18 cases. The sensitivity and specificity for PET were 83 and 83%, respectively. In patients with suspected disease, sensitivity was 94% compared to 65% in patients judged clinically disease free. The sensitivity of PET was 96% if suspicion of recurrence was based on a rise of CA125 alone. PET preceded the conventional diagnosis by a median of 6 months in patients judged clinically free of disease. The median relapse-free interval after a negative PET scan was 20 months. CONCLUSION: FDG PET provides the chance to detect recurrent ovarian cancer at an earlier stage during follow-up. Patients with a negative PET scan have a longer relapse-free interval than patients with a positive PET scan.
Ergonomic analysis of conditions prevailing during laparoscopy show that static holding work causes considerable problems. The surgeon's assistant is particularly affected, for example, by holding the endoscope optical system. To minimize strain for the entire operating team and to increase the range of activities that can be performed by the assistant, an automatic surgical camera-holding system was developed. Its value in clinical practice was tested in gynecologic laparoscopy, where it enabled the surgical team to work more comfortably.
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.
Thrombocytopenia (< 150,000/microliter) is a common finding, occurring in 7-8% of pregnancies. Some conditions, such as gestational thrombocytopenia pose no maternal or fetal risks. Idiopathic thrombocytopenic purpura (ITP) is an acquired haematologic disorder, common among children and adults, with unknown etiology and autoimmune pathogenesis. The incidence of severe fetal and neonatal thrombocytopenia is very rare, and neonatal intracranial hemorrhage is unlikely to be related to the mode of delivery. Alloimmune thrombocytopenia occurs with an incidence of 1/1,000 livebirths and is induced by a maternal alloimmunization against fetal platelet antigens. The incidence of intracranial haemorrhage in the fetus and neonate is the highest for any immune thrombocytopenia. The HELLP syndrome is a severe, unpredictable and life-threatening complication of preeclampsia, characterized by a triad of hemolysis, elevated liver enzymes and low platelet counts. HELLP syndrome develops in the third trimester but can occur postpartum. Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are syndromes of microangiopathic hemolytic anemia, and thrombocytopenia. During pregnancy, TTP usually presents in the second trimester, whereas HUS develops in the postpartum period. Heparin-induced thrombocytopenia type II is a serious, immune-mediated complication of heparin therapy.
OBJECTIVE: Preeclampsia is reportedly accompanied by increased plasma lipid peroxidation. However, to date the assays that have been applied to measure lipid peroxides have been relatively nonspecific. A highly specific high-performance lipid chromatographic-chemiluminescence technique was used here to measure lipid hydroperoxides in plasma and red blood cells of patients with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. STUDY DESIGN: Lipid peroxidation products, both lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and free radical scavenging enzyme activities were measured in either plasma or erythrocytes of patients with normal pregnancies (n = 36), preeclampsia (n = 28), or HELLP syndrome (n = 10). RESULTS: Whereas lipid hydroperoxides were undetectable (<0.02 micromol/L), plasma TBARS and glutathione peroxidase activity in plasma and erythrocytes were significantly increased in patients with HELLP syndrome. There were no differences in glutathione transferase and reductase activities or superoxide dismutase activity between the groups. CONCLUSIONS: We were unable to corroborate results of studies that suggested that increased TBARS are representative of circulating plasma lipid hydroperoxides in preeclampsia. However, elevated glutathione peroxidase activity and TBARS are in line with increased oxidative stress in preeclampsia.
Preeclampsia is associated with an increased platelet activation; however, there are few studies concerning platelet activation of the newborn. The aim of our study was to compare platelet activation in newborns of preeclamptic mothers to newborns of healthy mothers by using whole blood flow cytometry. Blood samples were obtained from 20 newborns (10 healthy controls, 10 cases of preeclampsia/HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome) during cesarean section. Antibodies against the following antigens were used as markers for platelet activation: CD 41, CD62P, CD 63, and platelet-bound fibrinogen. In addition to the basal platelet activation, the ability of platelets to undergo activation as a result of in vitro incubation with a weak agonist (adenosine diphosphate) was evaluated. A significant difference between the groups concerning basal platelet activation could only be seen for platelet-bound fibrinogen; the control group showed a higher extent of platelet activation (16.6 +/- 11.3 vs. 6.1 +/- 4.9; p = 0.03). Incubation with adenosine diphosphate in the control group resulted in minor increases of platelet activation, which was significant only for platelet-bound fibrinogen (16.6 +/- 11.3 vs. 42.5 +/- 22.1; p = 0.02). However, the preeclamptic group showed significantly increased levels of platelet activation for all used markers after in vitro activation (CD 41: 115.6 +/- 18.2 vs. 163.2 +/- 29.6; p = 0.002; CD62P: 2.4 +/- 0.4 vs. 3.9 +/- 0.3; p < 0.001; CD 63: 2.7 +/- 0.5 vs. 3.7 +/- 0.6; p = 0.002; platelet-bound fibrinogen: 6.1 +/- 4.9 vs. 55.1 +/- 9.1; p < 0.001). Preeclampsia or HELLP syndrome is therefore associated with an increased susceptibility to neonatal platelets, even against weak activators such as adenosine diphosphate. Whether this results from peculiarities in the fetal vascular environment or maternal influences is yet uncertain.
AIMS: To investigate localization and concentration of adhesion molecules in the human lower uterine segment during preterm parturition. METHODS: In a prospective study biopsy specimens from the lower uterine segment of 43 patients undergoing cesarean section at 24 + 0 to 36 + 4 weeks' gestation were immunostained for intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1, and the concentrations measured by enzyme immunoassay. The results were analyzed in relation to the degree of cervical dilatation (< 2 cm, 2- < 4 cm, > or = 4 cm) and duration of labor (< or = 6 h, > 6-12 h; > 12 h). RESULTS: Intercellular adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 were strongly expressed by capillary endothelium, endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 to only a minor degree. Intercellular adhesion molecule-1 concentration was greater at > or = 4 cm dilatation than at 2- < 4 cm and after > 12 h labor than after < or = 6 h. Endothelial leukocyte adhesion molecule-1 concentration was greater after > 12 h than after < or = 6 h. CONCLUSIONS: Premature labor is associated with up-regulation of adhesion molecules in the lower uterine segment.
AIMS: To determine the concentrations of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and interleukin-8 in the lower uterine segment during preterm parturition. METHODS: In 71 patients who delivered prematurely by non-elective cesarean tissue specimens were obtained from the lower uterine segment. The patients were grouped in relation to the stage of cervical dilatation (< 2 cm, 2- < 4 cm, > or = 4 cm), duration of labor (< or = 6 h, > 6-12 h; > 12 h), and parity (1 versus > 1). Cytokine concentrations in protein extracts of the tissue samples were measured using enzyme-linked immunosorbent assays. RESULTS: Median concentration of tumor necrosis factor alpha did not change, but that of interleukin-1 beta, interleukin-6, and interleukin-8 were significantly higher at 2- < 4 cm than at < 2 cm cervical dilatation (6.6, 67.7, and 125.8 versus 1.1, 17.6, and 22.2 pg/mg protein, respectively). The concentrations of interleukin-6 and interleukin-8 showed a further increase at > or = 4 cm (297.2 and 468.6 pg/mg, respectively), but for interleukin-1 beta a decrease was observed (0.6 pg/mg). Cytokine concentrations were not related to duration of labor or parity. CONCLUSIONS: Local inflammation-associated changes that are mainly related to the stage of cervical dilatation and to only a minor degree to uterine activity may play a crucial role in preterm parturition.
OBJECTIVE: To test the value of DNA image cytometry in the differential diagnosis of hyperplastic endometrial lesions and endometrial carcinoma on a series of 153 cases of simple hyperplasia (n = 71), complex hyperplasia (n = 28), complex atypical hyperplasia (n = 11) and endometrial adenocarcinoma (n = 43). STUDY DESIGN: Monolayer smears were prepared from three 50-micron-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen randomly, was determined using a TV image analysis system (CM-1, Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every case. Different DNA cytometric parameters and the mean nuclear area were calculated. RESULTS: Cases of adenocarcinoma and complex atypical hyperplasia (n = 54) were defined as clinically "positive" as these patients are normally treated by hysterectomy. The remaining cases of simple and complex hyperplasia (n = 99) were interpreted as clinically "negative" as conservative therapy is usually preferred. Requesting a specificity of > 90%, high sensitivity rates were calculated for ploidy imbalance (94%), mean ploidy (91%), diploid deviation quotient (91%), DNA stemline ploidy (87%) and 2c deviation index (85%), based on suitable thresholds. Entropy (76%), 5c exceeding events (63%), mean nuclear area (48%) and 9c exceeding events (6%) revealed lower sensitivity values. 5c Exceeding events (P = .0117) and mean nuclear area (P = .0392) were helpful in differentiating between atypical hyperplasia and endometrial carcinoma as the data distribution was significantly different with the U test. CONCLUSION: Our results indicate that DNA single cell cytometry is a highly relevant tool in the differential diagnosis of endometrial lesions and could be used as a complementary diagnostic method, especially in histomorphologically difficult cases.
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OBJECTIVE: To compare the effectiveness of prostaglandin E(2) intravaginal gel with the intracervical gel in patients with an unfavorable cervix. METHOD: In a prospective multicenter trial 470 patients with unfavorable Bishop scores (3-4) were randomized to receive prostaglandin vaginal gel (2 mg) or intracervical gel (0.5 mg). RESULTS: In patients with unfavorable Bishop scores the intravaginal application route resulted in a better cervical ripening, a shorter induction to delivery interval and a higher cumulative rate of deliveries during 24 h (P=0.01). CONCLUSION: Intravaginal instillation of prostaglandin E(2) gel for induction of labor is effective in patients with an unfavorable Bishop score of 3-4.
OBJECTIVE: To determine the concentration of endothelial cell adhesion molecules in the lower uterine segment during parturition at term. METHODS: We analyzed protein extracts from the lower uterine segments of 38 women who had nonelective cesareans at term. We measured concentrations of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1 by enzyme-linked immunosorbent assay. Subjects were grouped according to cervical dilatation (less than 2 cm, n = 10; 2 to less than 4 cm, n = 9; 4-6 cm, n = 9; more than 6 cm, n = 10) and duration of labor (up to 6 hours, n = 14; 6-12 hours, n = 10; 12-24 hours, n = 9; longer than 24 hours, n = 5) at the time of cesarean. RESULTS: The median concentration of intercellular adhesion molecule-1 increased significantly with increasing dilatation (from 2.24 ng/mg total protein at less than 2 cm to 6.73 ng/mg at 4-6 cm) and increasing duration of labor (from 2.53 ng/mg up to 6 hours to 5.90 ng/mg at 12-24 hours). However, this study did not have adequate statistical power to identify differences in concentrations of the other endothelial adhesion molecules. CONCLUSION: The results indicate that parturition at term is associated with expression of intercellular adhesion molecule-1.