[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.

Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters.

1. The release of acetylcholine was investigated in the human placenta villus, a useful model for the characterization of the non-neuronal cholinergic system. 2. Quinine, an inhibitor of organic cation transporters (OCT), reduced acetylcholine release in a reversible and concentration-dependent manner with an IC(50) value of 5 microM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 microM. 3. Procaine (100 microM), a sodium channel blocker, and vesamicol (10 microM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4. Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylcholine in a concentration-dependent manner with an IC(50) value of 2 microM. 5. Substrates of OCT subtype 1, 2 and 3 (amiloride, cimetidine, guanidine, noradrenaline, verapamil) inhibited acetylcholine release, whereas carnitine, a substrate of subtype OCTN2, exerted no effect. 6. Long term exposure (48 and 72 h) of villus strips to anti-sense oligonucleotides (5 microM) directed against transcription of OCT1 and OCT3 reduced the release of acetylcholine, whereas OCT2 anti-sense oliogonucleotides were ineffective. 7. It is concluded that the release of non-neuronal acetylcholine from the human placenta is mediated via organic cation transporters of the OCT1 and OCT3 subtype.

Hypoxia-stimulated expression of angiogenic growth factors in cervical cancer cells and cervical cancer-derived fibroblasts.

It is generally accepted that local growth of solid tumors and their ability to establish distant metastases are dependent on the formation of new blood vessels arising from preexisting ones (angiogenesis). The angiogenic response of the host is mediated by angiogenic molecules that are released from cancer and normal stroma cells, especially fibroblasts. The goal of the present study was to quantitatively compare the expression of the two most important angiogenic growth factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that of cervical cancer-derived fibroblasts (from one tumor/patient) under defined normoxic and hypoxic conditions in vitro. The growth kinetics of cervical cancer cells (HeLa and Me-180) and tumor-derived fibroblasts were evaluated in vitro under normoxic and hypoxic conditions. Growth factor concentrations in the cell culture medium were measured by ELISA and the secretion rates per cell were calculated. Under normoxic conditions, both the cervical cancer cells as well as the tumor-derived fibroblasts released VEGF and angiogenin. The secretion rate of both angiogenic factors was significantly higher in the stroma cells than in the tumor cells (P < 0.05). VEGF and angiogenin secretion is significantly higher in the stroma cells under hypoxia than in the tumor cells investigated (P < 0.05). The presented data support the concept that in cervical cancer non-neoplastic fibroblasts could play a pivotal role in the complex process of tumor angiogenesis.

The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic parameters and prognostic significance: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The objective of this study was to assess whether the presence of human papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer are correlated with several clinicopathologic parameters of well-defined prognostic significance and whether virologic parameters are predictors of long-term survival in cancer patients. Two hundred twenty three cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathologic parameters and survival data. HPV DNA was detected by PCR in 150 of 193 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histologic tumor types, node status, tumor oxygenation, blood vessel invasion, and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox regression analysis (RR 2.856, P < 0.003 resp. RR 3.444, P < 0.0001). In the multivariate analysis, however, HPV DNA status failed to be of prognostic relevance. Exclusively HPV 16 appears to have an independent impact on the overall survival in cervical patients (RR 3.653, P < 0.002). We conclude that the detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors of uterine cervix remains to be investigated in further studies, and the exact mechanisms by which HPV influences the prognosis of cervical cancer patients have to be defined.

Human papillomavirus (HPV) DNA in primary cervical cancer and in cancer free pelvic lymph nodes--correlation with clinico-pathological parameters and prognostic significance.

OBJECTIVE: To assess whether the presence of human papilloma virus (HPV) DNA and/or several genotypes of HPV DNA in primary cervical cancer and cancer free pelvic lymph nodes are correlated with several clinicopathological parameters of well-defined prognostic significance and whether virological parameters are predictors of long-term survival in cancer patients. PATIENTS AND METHODS: 223 cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the high sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathological parameters and survival data. RESULTS: HPV DNA was detected by PCR in 150 of 203 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histological tumor types, node status, blood vessel invasion and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox Regression Analysis (RR 2.856, p < 0.003 resp. RR 3.444, p < 0.0001). The presence of HPV DNA in cancer free pelvic lymph nodes was significantly correlated to the concomitant manifestation of pelvic lymph node metastases (RR 3.1, p < 0.0001). In the multivariate analysis, however, HPV DNA in primary tumor and in negative pelvic lymph nodes failed to be of prognostic relevance. Exclusively, HPV 16 appears to impact independently on the overall survival in cervical cancer patients (RR 3.653, p < 0.002). CONCLUSION: The detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors and cancer free pelvic lymph nodes remains to be investigated in further studies. The exact mechanisms by which HPV influence the prognosis of cervical cancer patients have to be defined.

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.

(A)symptomatic necrotizing arteritis of the female genital tract.

AIMS: The vasculitides represent a heterogenous set of disorders that differ in prognosis and response to therapy. Beside systemic vasculitides, the development of localized forms of arteritis is well known though uncommon and the etiopathogenesis is not yet definitely clear. METHODS: Patients with necrotizing arteritis of the female genital tract proven by histology are studied in a retrospective analysis. RESULTS: Three cases of necrotizing arteritis with histological features of panarteritis nodosa apparently confined to the female genital tract are presented. None of these patients had prior history of systemic vasculitis. The acute necrotizing vasculitis was confined only to the uterine cervix in two patients and involved all the internal genital organs in the third patient. The patients have been observed for up to 4 years without any therapy for these lesions and without any manifestation of systemic vasculitic progression. CONCLUSION: It is to speculate that focal arteritis of the female genital tract is a benign form of panarteritis nodosa or moreover a totally different entity with identical morphogenesis but possibly different pathogenesis. Furthermore it seems to be important to be aware of the specificity of focal arteritis in female genital tract as distinct from the generalized form to prevent unnecessary surgical or chemotherapeutical therapy for this lesion. The benign entity of local arteritis in the female genital tract is discussed in contrast to the severe prognosis of systemic panarteritis nodosa.

[Optimizing performance documentation in gynecology--assistance from the internet]. / Optimierung der Leistungsdokumentation in der Frauenheilkunde--Hilfestellungen aus dem Internet.

The documentation of operations in the field of gynecology and obstetrics is regulated by social laws in Germany. Only by optimal encoding of diagnoses and procedures an efficient cashing with the health insurance's can be achieved. This requires profound knowledge of the invoice modalities and usually support by computer systems. The Internet offers in this respect some assistance, which in the following is pointed out and evaluated critically.

[D-dimer, thrombin-antithrombin III-complex (TAT) and prothrombin fragment 1+2 (PTF). Parameters for monitoring therapy with low molecular-weight heparin in coagulation disorders]. / D-Dimer, Thrombin-Antithrombin III-Komplex (TAT) und Prothrombinfragment 1 + 2 (PTF). Parameter zur Uberwachung der Therapie mit niedermolekularem Heparin bei Gerinnungsstörungen.

Two groups of 15 patients each with disseminated intravascular coagulation in association with septic disease were treated with low-molecular-weight heparin (lmw-heparin) in different dosages (group I: 1.5-5 IE/kg body weight (BW) per hour; group II: 8-15 IE/kg BW). We studied the levels of D-dimer, thrombin-antithrombin III complex (TAT), prothrombin fragments 1 and 2 (PTF), and global tests of coagulation like prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT) and platelet count, plasminogen activation (PA) and fibrinogen concentration to estimate the success of heparin therapy in the two groups. TT and fibrinogen concentration were not suitable to follow the course of the coagulation disorder, PT, PTT, platelet count progressively PA, D-dimer, TAT, and PTF normalised progressively after heparinisation. However, only the last three parameters were sensitive enough to show different effects of variable dosages of lmw-heparin. D-dimer, TAT, and PTF levels declined in proportion with heparin concentrations, and thus appear to be the most useful parameters for monitoring the therapeutic effect of heparin in septic coagulopathies.

[Pre- and postpartum hemostatic characteristics in pregnancy-related hypertension and pre-eclampsia in comparison with normotensive pregnancies]. / Prä- und postpartale hämostaseologische Besonderheiten bei schwangerschaftsinduzierter Hypertonie (SIH) und Präeklampsie verglichen mit normotensiven Schwangerschaften.

Pregnancy is accompanied by a physiological activation of intravascular coagulation; however without disorder. Normal markers of coagulation are unchanged despite activation. Special coagulation parameter--such as Thrombin-Antithrombin-III-complex (TAT) or D-Dimer are increased also in normal pregnant women. Pregnancy induced hypertension (SIH) and preeklampsia may be associated with a disorder of coagulation that precedes the well known clinical manifestation of hypertension. Therefore it was the aim of the study to distinguish both the pregnancy induced hypertension (15 patients) and preeklampsia (10 patients) as far as it is possible by coagulation parameters such as thrombin generation (by TAT), fibrinolysis (by D-Dimer), AT-III, platelets and others comparing them with 25 normotensive pregnancies. In preeklampsia, the results showed that clinical signs were associated with simultaneous coagulation abnormalities. TAT and D-Dimere are significant increased whereas a decrease of AT-III and platelets was observed. There are no significant differences between SIH and normal pregnancies. Three days after delivery there was an increase of D-Dimer, AT-III and platelets and a decrease of TAT-complex in all groups. For risk pregnancy, the parameters TAT and D-Dimer may be useful as screening test. They although may support confirming the diagnosis of preeklampsia.

Perinatal database in Germany.

By collecting standardized data from up to 600,000 deliveries per year in Germany a nation-wide database has been established in recent years enabling not only regional and overregional quality control, but also the scientific analysis of rare maternal and fetal complication. During the observation period of 10 years the understanding of perinatal risk factors has considerably improved and the perinatal mortality has declined from 9.4 to 6.4 (per 1,000 deliveries). From the huge amount of calculations typical results are presented.

[Information processing and perinatology--experiences with GebLan at the Mainz University Gynecologic Clinic]. / Informationsverarbeitung und Perinatologie--Erfahrungen mit GebLan an der UFK Mainz.

Modern perinatal information management is a subject of growing complexity. The requirements for perinatal computer applications changed totally during the last years. Today we need applications with a high integration level of data from diverse sources, a modern graphical interface and a powerful data management for example a Client Server architecture. The experience with the perinatal documentation and information system "GebLan" in a local area network is very sufficient though we conclude that stand-alone-systems should only be used in smaller obstetrical departments.

[Persistent granulocytosis and hyperuricemia after a single G-CSF injection (Filgrastim) in treatment of chemotherapy-induced myelosuppression in metastatic breast carcinoma]. / Anhaltende Granulozytose und Hyperurikämie nach einmaliger G-CSF-Injektion (Filgrastim) zur Therapie einer chemotherapie-bedingten Myelosuppression beim metastasierten mammakarzinom.

We report about a patient with metastatic breast cancer treated with chemotherapy regime (CMF), who developed a febril leukopenia as well as a hyperuricemia. A single subcutaneous application of 300 micrograms Filgrastim led to a severe overstimulation with leukocytosis of max. 50,000 for about 8 days and hyperuricemia.

Risk weighing in twin pregnancy.

Multiple pregnancies are more often associated with complications than singleton pregnancies. In our retrospective study of 613 twin pregnancies the most important risk factors in twin pregnancies were premature labour before the 37th week of gestation and the premature rupture of the membrane. The increase of perinatal mortality and morbidity for twins might be primary the result of premature delivery.

Thiopentone, thiopentone/ketamine, and ketamine for induction of anaesthesia in caesarean section.

Seventy-five healthy patients were randomly allocated to receive thiopentone, thiopentone/ketamine or ketamine for induction of anaesthesia for elective Caesarean section. Thiopentone resulted in the most pronounced and ketamine in the smallest drop in blood pressure, while the combination induced only moderate haemodynamic changes. Intra-operative awareness occurred in one patient in the thiopentone group, six of the ketamine patients had nightmares, and one patient of the combination group reported pleasant dreams but no awareness. The muscle tone of neonates in the thiopentone group was more reduced than in neonates in the other two groups. Infants delivered after uterine incision-to-delivery intervals exceeding 3 min more often had Apgar scores < 7 than those delivered in less than 3 min.

[Value of prostaglandins in a pre-eclampsia-equivalent animal model]. / Stellenwert der Prostaglandine in einem Präeklampsie-äquivalenten Tiermodell.

Pregnancy-induced hypertension is no uniform disease with one cause and one pathophysiologic course. On the contrary it seems to be a multifactorial event with a very different symptomatology and a variable damage of various organs. Because of the heterogeneity of the disease and the difficulty of differentiation these various kinds of courses clinical studies, mostly retrospectively done, have to be criticized. The aim of this study is to examine vasoactive regulation systems by means of a standardized animal model, using wistar rats. A systemic hypertension could be achieved only in pregnant animals with aid a infrarenal aortic stenosis. Non pregnant and simulated operated pregnant animals are the control group. In the normotensive pregnant rats there was an elevation of all renal prostanoids: PGI2, TxB2 and PGE2. On the contrary hypertensive pregnant rats showed a decrease of all eicosanoids, prononcigated of PGE2.

[Hypertensive complications in pregnancy--a special evaluation of the Rhineland-Pfalz perinatal study]. / Hypertensive Komplikationen in der Schwangerschaft--eine Sonderauswertung der Perinatalerhebung Rheinland-Pfalz.

In a special analysis of the perinatal database Rheinl.-Pfalz of the years 1989 and 1990 1,876 pregnancies with the risk-factor "gestosis" (2.4% of all deliveries) were evaluated. In comparison to all deliveries (n = 78,250) significantly different incident-rates could be observed: Sterility, working during pregnancy, nationality, parity, psycho-social stress, multiples, adipositas, diabetes mellitus, pathological increase of body weight, urinary infection, number and duration of antenatal hospitalisation. Prematurity and fetal retardation as well as placental insufficiency, pathological antenatal CTG, green amniotic fluid and intrapartel acidosis was seen much more often in the risk group, resulting in a much higher rate of caesarean section (50.1 versus 13.7%) and an increased maternal and fetal morbidity. Perinatal mortality was twice as high in the risk group compared to the control. Thought data quality is limited in this study covering a very larger area, the results underline the unchanged importance of hypertensive disorders in perinatology.

[Pre-eclampsia versus essential hypertension--the course of pregnancy, labor and fetal outcome]. / Präeklampsie versus essentieller Hypertonus--Schwangerschaftsverlauf, Geburt und Fetal Outcome.

By means of an exact nephrologic examination 6 weeks post partum of 128 patients with hypertension in pregnancy an exact classification in preeclampsia (46 per cent), chronic hypertension (34%) and superimposed preeclampsia (13 per cent) is possible. In cases of essential hypertension a hypotensive therapy is necessary.

[The older primipara--an obstetrical risk group?]. / Die späte Erstgebärende--Ein geburtshilfliches Risikokollektiv?

While the number of the "elderly primigravida" seems to increase in some perinatal centers, we compared pregnancy, delivery mode and fetal outcome of 416 patients with a matched pair group of 15 year younger primigravida. While the rate of caesarean section and vacuum extraction rises up to 40%, we could not found any difference for the fetal outcome. Though we conclude that modern perinatal management in case of the elderly primigravida is very effective and allows normal fetal outcome.