Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer.

BACKGROUND: Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. METHODS: Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. RESULTS: Both uPA (p=0.011) and PAI-1 (p=0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p=0.021 for uPA and p=0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage (p=0.003) and with histological grading (p=0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. CONCLUSION: The combination of high cytosolic concentrations of uPA (>5 ng/mg total protein) and high PAI-1 (>20 ng/mg total protein) may reveal a group of patients with increased risk of progression.

The rheological changes after cesarean section: The influence of low molecular weight or unfractionated heparin on the rheological properties of blood.

Thromboembolic complications remain an important cause of maternal mortality. The present recommendations favour for prophylaxis unfractionated (UFH) and low molecular weight heparin (LMWH). We investigated 150 pregnant women before and after cesarean section in three randomized groups. Fifty women received no prophylaxis (group I), 50 women UFH two times 5000 IU/day (group III) and 50 women Dalteparin 5000 U/day (group II). We determined the blood count, the rheological parameters and cholesterol, triglycerides, D-dimer, fibrinogen and the anti-Xa-level. We found a classical hemodilution, with increase of erythrocyte aggregation and plasma viscosity postoperatively. The fibrinogen turnover and D-dimer concentration were elevated. The patients with Dalteparin prophylaxis showed lower thrombin activation, minor changes in the cholesterol and triglycerides level and an improvement of red cell deformability in low shear regions. Our results demonstrated an influence of Dalteparin on the rheological parameters post surgery. The DVT incidence was 1.33% generally and occurred only in the Control group and in women with unfractionated heparin. We observed no side effects such as major bleeding, osteopenia or allergy.

Successful treatment of life-threatening bleeding after cesarean section with recombinant activated factor VII.

Hemorrhagic shock developed in a 29-year-old nullipara without coagulopathy after emergency caesarean section. Treatment with uterotonic drugs, prostaglandins, and conservative procedures with transfusion of packed red cells and fresh-frozen plasma failed to control the diffuse vaginal and uterine bleeding. Finally an intravenous bolus injection of 90 microg/kg recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark), was given and showed success within 20 minutes after administration, without any side effects.

Fetal hemorheology in normal pregnancy and severe preeclampsia.

Hemorheological parameters were determined in 45 pairs of mothers with severe preeclampsia and their newborns in comparison with 45 women with uncomplicated pregnancies and their newborns. In both groups we investigated red cell deformability, the plasma viscosity, the red cell aggregation (during stasis and low flow), the macromolecules fibrinogen and factor VIIIR:Ag (VWF), and the blood count parameters hemoglobin, hematocrit, white cells, platelets, reticulocytes, MCV, MCHC. Cholesterol and triglycerides were correlated to the parameter of red cell deformability measured as red cell elongation. We found a significant lower plasma viscosity, red cell aggregation, fibrinogen, cholesterol, triglycerides and VWF in cord blood with a close association between plasma viscosity and fibrinogen (r = 0.56, p = 0.001). The red cell deformability measured as red cell elongation was statistically higher in the cord blood compared to the mothers and associated with a higher MCV. In contrast the MCHC values remained unchanged. Hematocrit and hemoglobin in the cord blood were higher than in the mothers. The incidence of fetal hyperviscosity-polycytemia syndrome in women with severe preeclampsia was between 4.7% and 4.9%. An elevated red cell aggregation was found in 2.8% (stasis) and 4.8% (low flow state), respectively. We conclude that in fetal blood the higher hematocrit and the presence of larger red cells do not cause impaired fetal hemorheology.

[Severe virilization in a postmenopausal woman: a case report]. / Ausgeprägte Virilisierung in der Postmenopause -- eine Falldarstellung.

Severe postmenopausal virilization is a rare event in clinical practice. To evaluate ovarian or adrenal hyperandrogenism endocrine tests and imaging are useful diagnostic tools. We report a case of a postmenopausal woman with hirsutism and androgenetic alopecia. A malignant cause for the present disorder could be excluded by imaging. Selective venous sampling was administered with increased testosterone level of the right adrenal vein. Right adrenalectomy and right oophorctomy was recommended.

[Perinatal outcome of premature infants weighing less than 1500 g]. / Untersuchungen des perinatalen Zustandes bei frühgeborenen Kindern mit weniger als 1500 g.

BACKGROUND: Prematurity is a main issue in modern obstetrical care. The purpose of the present study was to evaluate the perinatal outcome of premature infants weighing less than 1500 g according to the mode of delivery. PATIENTS AND METHODS: 122 patients with infants weighing less than 1500 g were enrolled in this retrospective study (26 to 32 weeks of gestation). The perinatal outcomes of 26 infants born by vaginal delivery were compared to 96 infants delivered by caesarean section. RESULTS: The rates of rupture of membranes, preterm labour and intravenous tocolysis were significantly increased in patients after vaginal delivery. Preeclampsia and pathological cardiotocograms were increased in patients after caesarean section. Infants born by vaginal delivery showed a significant increase of peri- and intraventricular haemorrhage grade III, periventricular leukomalacia, C-reactive protein 24 hours postpartum and mortality until the seventh day of life. However, the rate of bronchopulmonary dysplasia was significantly increased in infants born by caesarean section (p < 0.05). CONCLUSIONS: These data suggest that the mode of delivery affects the perinatal outcome of infants weighing less than 1500 g. Based on the results of the present study, it appears unclear which mode of delivery should be preferred, depending on particular material and fetal factors.

[Inhibins and Activin A in hypertensive Disorders of Pregnancy and HELLP-Syndrome]. / Inhibine und Aktivin A bei hypertensiven Schwangerschaftserkrankungen und HELLP-Syndrom.

OBJECTIVE: Are serum concentrations of the ovarian glycoproteins inhibin A, inhibin B, pro-alpha-C and activin A different in normotensive, chronical hypertensive or pregancies complicated by preeclampsia or HELLP-syndrome? What are the clinical consequences? METHODS: Serum concentrations of inhibin A, inhibin B, pro-alpha-C, and activin A of 99 women (37 normotensive patients, 23 patients with chronical hypertension, 25 women with preeclampsia and 14 patients with HELLP-syndrome) at different stages of pregnancy were determined by high specific ELISAS. RESULTS: During pregnancy serum levels of all parameters increased continually and fell rapidly within parturition. Activin A and inhibin B levels showed significant higher serum concentrations in patients with preeclampsia and - even more pronounced - in patients with HELLP-syndrome. Normotensive and chronically hypertensive patients were not different. CONCLUSION: Activin A and inhibin A appear to be viable candidates as laboratory parameters for detection of pregnancy induced hypertension. Maybe furthermore both parameters will allow the discrimination between chronic hypertension and hypertension induced by pregnancy.

Hemorheological changes in women with severe preeclampsia.

The objective of this study was to determine the differences of hemorheological parameters in association to haematological tests in patients with severe preeclampsia (blood pressure (diastolic) > 100 mm Hg, blood pressure (systolic) > 180 mm Hg and proteinuria > 3 g/24 h). Blood samples of 45 primigravidas by hospital admission were studied. The control group were 45 pregnant women--age and weight matched--with normal blood pressure and without obstetric complications. We measured red cell aggregation (stasis, low shear), red cell elongation with the ectacytometer, blood cell indices (Hct, Hbg, MCV, MCHC, reticulocytes, white cells, platelets), fibrinogen haptoglobin and factor VIIIR:Ag, cholesterol and triclycerides. In comparison between patients with severe preeclampsia and normal pregnant women we found statistically elevated values of hematocrit, hemoglobin, red cell aggregation (stasis, low shear rate), MVC and factor VIIIR:Ag. Non-significant changes were observed in values of plasma viscosity, white cells, platelets, haptoglobin, MCHC, reticulocytes, triglycerides and cholesterol. The red cell deformability measured as cell elongation was statistically reduced by high shear stress application in patients with severe preeclampsia. Our results suggest that hemorheological parameters play an important role in severe preeclampsia, especially at microcirculatory regions with high shear stress such as intervillous space of placenta.

Early postpartum hyponatremia in a patient with transient Sheehan's syndrome.

In modern day health care, Sheehan's syndrome is a rare disorder affecting the postpartum period. We present a case of a 33-year-old woman with atonic hemorrhage developing a transient Sheehan's syndrome associated with hyponatremia six days postpartum. Evaluation of cranial computer tomography and magnetic resonance imaging of the pituitary demonstrated normal finding. Immediate replacement therapy using sodium, chloride, hydrocortisone, fludrocortisone and levothyroxine revealed regression of the Sheehan's syndrome to complete recovery. The present report shows that Sheehan's syndrome can be associated with hyponatremia and illustrates the need to include hyponatremia as an initial symptom in the differential diagnosis of Sheehan's syndrome.

[Medical informatics in obstetrics and gynecology - the actual challenge?]. / Was sind die aktuellen Aufgaben? - Medizinische Informatik in der Frauenheilkunde.

There is common agreement about the importance of information management systems in obstetrics and gynecology. Those systems are necessary tools for medical quality management and are essential for the actual preparation for the age of the "diagnosis related groups" that will be introduced in Germany next year. Nevertheless there are only small scientifically activities to improve information management systems and to evaluate their performance. Great efforts are necessary to develop new features and not to loose the conflict between the needs of the physicians and their patients and the needs and demands of hospital administrative authorities.

[Circadian blood pressure rhythm in preeclampsia as a predictor of maternal and obstetrical outcome]. / Zirkadiane Blutdruckrhythmik bei der Präeklampsie: Ein Prädiktor für die maternale und geburtshilfliche Situation?

BACKGROUND: Preeclampsia is a pregnancy-induced multiorganic disease. The incidence is 5 - 7 % in all pregnant women. To assess the value of circadian blood pressure rhythm in preeclamptic women, 24-hour blood pressure monitoring might be useful. The purpose of this study was to determine the predictive value of circadian blood pressure rhythm for the maternal and obstetrical outcome in patients with mild preeclampsia. PATIENTS AND METHODS: Sixty-six patients with mild preeclampsia underwent 24-hour blood pressure monitoring between 29 and 39 weeks gestation. Twenty-eight patients with normal circadian blood pressure rhythm were compared with thirty-eight patients with suspended circadian blood rhythm. RESULTS: There was no difference in age, body mass index, gravidity, parity, miscarriage, or fetal outcome between the two groups. The rate of secondary caesarean section was 39.5 % in the suspended circadian blood pressure group and 21.4 % in the normal circadian blood pressure group, respectively (P = 0.03). CONCLUSIONS: In patients with mild preeclampsia, the circadian blood pressure rhythm appears to be unsuitable as a screening test. Further research is required for more etiological and pathophysiological insights into the development of clinically useful tools with predictive value.

[Principles and advanced techniques for better internetpresentations in obstetrics and gynecology]. / Prinzipien und aktuelle Techniken der Internetpräsentation in der Frauenheilkunde.

Internet presentations are common tools for better medical communication and better scientific work. Meanwhile a great number of gynecological and obstetrical institutions present data via the world wide web within a wide range of quality and performance. Specific HTML editors offer quick and easy presentations, but only advanced internet techniques enable interesting multimedia presentations. N-tier applications are the future standard and we must integrate them in general informatical systems. New Concepts, actual tools and general problems will be discussed and new principles similar to actual E commerce techniques are able to solve our special medical demands.

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD-II) activity in human placenta: its relationship to placental weight and birth weight and its possible role in hypertension.

It has been assumed that low birth weight and high placenta weight were key factors for predicting hypertension in human adulthood. A deficiency in placental 11 beta-HSD-II enzyme activity was supposed to be the underlying cause. To possibly establish 11 beta-HSD-II as a leading factor, we determined 11 beta-HSD-II activities in 133 healthy pregnancies, 21 proteinuric pregnancies complicated by pregnancy-induced hypertension (PIH), 26 non proteinuric PIH pregnancies and 15 pregnancies complicated by fetal growth restriction (32nd-41st gestational week). We could not identify differences in 11 beta-HSD-II activity between pregnancies with the rare combination of small babies with big placentas and others (p = 0.59; Kruskal-Wallis test). And although there was no correlation between 11 beta-HSD-II activity and birth weight, in the control gestational age correlated with 11 beta-HSD-II activity (r = 0.22; p < 0.05; Spearman). 11 beta-HSD-II activity in the proteinuric PIH group was significantly higher than in the controls (11.7 pmol/min/mg prot.; range 10-13.2 vs. 7.9; range 7.0-9.1; p < 0.05). The lowest, but not significant, enzyme activities were in the IUGR group (5.8 pmol/min/mg prot.; range 4.0-9.2). In this group, analysis of variance detected a correlation between enzyme activity and placental weight. In conclusion, we could not confirm that placental 11 beta-HSD-II deficiencies act as an indicator for the risk of adult hypertension in small fetuses with large placentas. However, in growth restriction 11 beta-HSD-II activity might play a role. To clarify the influence in this group, further research is needed. Increased 11 beta-HSD-II activities with gestational age in the control may serve to sustain fetal adrenal steroid genesis and to prepare the fetus for autonomic life.

Concentrations of inhibins and activin in women undergoing stimulation with recombinant follicle-stimulating hormone for in vitro fertilization treatment.

OBJECTIVE: To investigate the influence of human recombinant follicle-stimulating hormone (FSH) on circulating serum concentrations of the ovarian proteohormones inhibin A, inhibin B, pro alpha-C, and activin A and serum levels of estradiol after down-regulation with GnRH analogue. DESIGN: Serum concentrations of ovarian proteohormones and estradiol. SETTING: Academic clinical practice. PATIENT(S): 30 women who underwent assisted reproductive techniques. INTERVENTION(S): Blood samples were analyzed for inhibin A, inhibin B, pro alpha-C, activin A, and estradiol during IVF treatment at points coinciding with pituitary down-regulation, stimulation with recombinant FSH, ovulatory triggering, and the luteal phase of the cycle. RESULT(S): Activin A levels did not change with recombinant FSH stimulation. In women with a sonographically detected leading follicle >17 mm in diameter, levels of inhibin A, pro alpha-C, and estradiol increased significantly (P<.05). The increase in inhibin B level was not statistically significant. In patients without adequate follicle development during FSH stimulation, serum levels of inhibins remained low and did not significantly deviate from values measured before stimulation. CONCLUSION(S): Inhibin A and pro alpha-C are effective markers of follicular development and may be effective additions to estradiol as a marker.

The role of intravenous volume expansion in moderate pre-eclampsia.

We examined the hemodynamic and hemorheological effects of intravenous volume expansion in women with pre-eclampsia. 20 untreated women with moderate pre-eclampsia were randomized to receive a 500 ml infusion over 4 h of either hydroxyethylstarch (HAES steril 10%, HES) or NaCl 0.9% solution. After completion of the infusion trial all patients received oral antihypertensive drugs, bed rest and free sodium and water intake. The hemodynamic responses were measured by impedance cardiography. Hemorheological parameters and blood pressure were measured before and after (24 h later) infusion. The HES infusion but not NaCl leads to a significant reduction of hematocrit and erythrocyte aggregation. In addition to that there was a nonsignificant increase of the cardiac index in the HES-group but no changes in the heart rate. Intravenous volume expansion in women with pre-eclampsia with a long acting colloid like hydroxyethylstarch is associated with a significant influence on the flow properties (hematocrit and erythrocyte aggregation) of blood.

Inverse correlation between baseline inhibin B and FSH after stimulation with GnRH: a study of serum levels of inhibin A and B, pro alpha-C and activin A in women with ovulatory disturbances before and after stimulation with GnRH.

OBJECTIVE: Interest has focused recently on the influences of the polypeptide factors inhibin and activin on the selective regulation of the pituitary secretion of gonadotropins. DESIGN: Measurement of the concentrations of inhibin-related proteins in relation to the changes in pituitary gonadotropin (FSH, LH) parameters, after GnRH stimulation with a bolus injection of 100 microg gonadorelin, in 19 women with ovulatory disturbances. METHODS: Serum levels of inhibin A and B, activin A, and pro alpha-C were measured using sensitive ELISA kits. RESULTS: Within 60 min after GnRH stimulation, FSH values doubled from 5 to 10 mU/ml (P < 0.001). LH increased 12-fold from 2 to 24 mU/ml (P < 0.001). Activin A showed a significant decrease from 0.47 to 0.36 ng/ml (P < 0.001), whereas pro alpha-C increased from 127 to 156 pg/ml (P = 0.039). The median inhibin A concentration did not show a significant change between baseline and the 60 min value, whereas inhibin B was characterized by a minor, but not significant, increase in the median from 168 to 179 pg/ml (P = 0.408). A significant inverse correlation (P = 0.014) with a mean coefficient of correlation of 0.5516 was found, demonstrating a strong relationship between high inhibin B baseline levels and a small increase of FSH after 60 min. CONCLUSION: Our results show an interesting correlation between the baseline inhibin B and the change in FSH before and after GnRH stimulation. A high baseline inhibin B implies only a minor increase of FSH after 60 min.

[Information processing in the gynecological endocrinological laboratory. Current concepts and integration strategies]. / Informationsverarbeitung im gynäkologisch-endokrinologischen Labor. Aktuelle Konzepte und Integrationsstrategien.

While computer applications are widely accepted in clinical chemical departments, small numbers of computer systems are used in gynecological endocrinological laboratories. Modern applications should be integrated in local area networks and clinical information systems that improve communication and data exchange within hospitals and the outer resources. Better communication may improve medical quality and will lead to a better therapy for gynecological endocrinological patients.

[P53-status in primary ovarian carcinomas, ovarian metastases of neoplasms in other sites and benign ovarian tumors: predictive value in comparison to histopathological parameters]. / P53-Status in primären Ovarialkarzinomen, Ovarialmetastasen von Fremdtumoren und benignen Ovarialtumoren: Wertigkeit als Prognosefaktor im Vergleich zu histopathologischen Parametern.

OBJECTIVE: The purpose of this study was to determine whether the tumor suppressor gene p53 can be used as a prognosis factor to assess individual patient risk in primary ovarian carcinoma. MATERIALS AND METHODS: The concentration of the mutated, as well as the wild type p53 was examined in 98 cases of ovarian carcinoma. Among 98 ovarian tumors examined, 77 were primary carcinomas, 14 tumors were metastasis of foreign tumors, and 7 were benign ovarian tumors. The pan-53 ELISA from Fa. Dianova was used to test for the p53 protein. RESULTS: The p53 protein concentration exhibited a wide range in the different tissue samples. Benign tumors contained significantly lower p53 concentrations than malignant tumors. After the data was analyzed using Kaplan-Meier, a p53 concentration of 507.1 pg/ml was established as cut-off point for assessing cancer prognosis as good or poor. Patients exhibiting p53 concentrations over 507.1 pg/ml had a median life expectancy of 20 months, and patients exhibiting lower tumor concentrations of p53 had a life expectancy of over 70 months. A significant relationship between patient life expectancy could also be shown for tumor stage and type, whereas not for tumor grading. CONCLUSIONS: Based on the results of this study, the routine measurement of p53 may allow for a better prognostic assessment of life expectancy of patients with primary ovarian carcinoma.

[Needle biopsy vs. conventional surgical biopsy - biochemical analysis of various prognostic factors]. / Vergleich der biochemischen Analyse verschiedener Prognosefaktoren zwischen Stanzbiopsie und intraoperativ gewonnenem Tumormaterial beim Mammakarzinom.

OBJECTIVE: In which way is the biochemical analysis of fine needle biopsy comparable to the biochemical analysis of conventional surgical biopsy samples in the examination of prognosis factors in mammary carcinomas. MATERIAL AND METHODS: Conventional surgical biopsy and fine needle biopsy were performed on 63 mammary carcinomas. The results from the biochemical analysis of tissue samples, from each form of biopsy, with respect to estradiol and progesterone receptor, UPA and PAI-1, as well as Kathepsin D and the EGF receptor, were compared and statistically analyzed. RESULTS: When compared to conventional tissue biopsy samples, the sensitivity and specificity of the measured prognosis factors in fine needle biopsy tissue were variable for each parameter, but fell within the statistically safe margin of 86 to 100%. CONCLUSIONS: The biochemical analysis of the prognosis factors found in fine needle biopsy samples showed that fine needle biopsy is a viable alternative to intraoperative conventional surgical biopsy.

[Value of p53, urokinase plasminogen activator, PAI-1 and Ki-67 in vulvar carcinoma]. / Untersuchungen zu p53, UPA, PAI-1 und Ki-67 beim Vulvakarzinom.

OBJECTIVE: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors. MATERIAL AND METHODS: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences. RESULTS: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients. CONCLUSIONS: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201.