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Cardiac anesthesiologists are commonly confronted with perioperative changes of serum lactate levels. Several mechanisms, including those iatrogenic, may play a role this finding. High dose insulin administration in the intraoperative setting can cause significant electrolyte disturbances such as hypophosphatemia, which may in turn result in severe lactic acidosis. We present two patients who required escalating insulin doses during cardiac surgery, and subsequently developed severe hypophosphatemia and lactic acidosis.

Giovanni Battista Morgagni is considered the Father of Pathology and contributed much to our early understanding of neuropathology. For example, he introduced the concept that diagnosis, prognosis, and treatment of disease must be based on an exact understanding of the pathologic changes in anatomic structures. Additionally, he contributed to what would become the discipline of neurosurgery and, for example, performed trepanation for head trauma.It is the contributions of such early pioneers as Morgagni that our current understanding of the neurosciences is based.

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of NPLD and taxanes. This phase II study was performed to evaluate the efficacy and safety of the NPLD and docetaxel in patients with metastatic breast cancer.A total of 51 patients were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) in 3-weeks intervals for up to eight cycles.The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9-13.1 months) and 25 months (95% CI, 22.1-29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1-16.9). The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents and of anthracycline/taxane combinations. There were no symptomatic cardiac averse events and mild asymptomatic LVEF changes were reported in five patients.The combination of NPLD and docetaxel is well tolerated and has high antitumour activity in MBC patients.

Introduction: Sporadic inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive asymmetric extremity weakness, oropharyngeal dysphagia, and the potential for exaggerated sensitivity to neuromuscular blockers and respiratory compromise. The authors describe their management of a patient with IBM undergoing urgent orthopedic surgery. Case Presentation: An 81-year-old man with IBM suffered a left intertrochanteric femoral fracture after falling down stairs. His IBM caused progressive left proximal lower extremity, bilateral distal upper extremity weakness (left > right), and oropharyngeal dysphagia (solid food, pills). He denied dyspnea, exercise intolerance, and a history of aspiration. Because respiratory insufficiency resulting from diaphragmatic dysfunction and prolonged duration of action of neuromuscular blockers may occur in IBM, the authors avoided using a neuromuscular blocker. After applying cricoid pressure, anesthesia was induced using intravenous lidocaine, propofol, remifentanil followed by manual ventilation with inhaled sevoflurane in oxygen. Endotracheal intubation was accomplished without difficulty; anesthesia was then maintained using remifentanil and sevoflurane. The fracture was repaired with a trochanteric femoral nail. The patient was extubated without difficulty and made an uneventful recovery. Conclusions: In summary, there is a lack of consensus about the use of neuromuscular blockers in patients with IBM. The authors avoided these drugs and were able to easily secure the patient’s airway and maintain adequate muscle relaxation using a balanced sevofluraneremifentanil anesthetic. Clinical trials are necessary to define the pharmacology of neuromuscular blockers in patients with IBM and determine whether use of these drugs contributes to postoperative respiratory insufficiency in these vulnerable patients.

Fragestellung: Ziel der Untersuchung war es, die Pravalenz von Gerinnungsstorungen bei Patientinnen mit drei oder mehr aufeinander folgenden, spontanen Fruhaborten zu evaluieren. Zusatzlich sollte ein moglicher Zusammenhang zwischen dem Vorliegen von Antiphospholipid-Autoantikorpern und einer hereditaren Thrombophilie bei Frauen mit habituellen Aborten untersucht werden. Material und Methodik: Bei 20 Patientinnen mit habitueller Abortneigung wurden die folgenden plasmatischen Gerinnungsuntersuchungen durchgefuhrt: Prothrombinzeit nach Quick, aktivierte Thromboplastinzeit (aPTT), Protein S, Protein C, Antithrombin III, Fibrinogen und Plasminogen. Zusatzlich erfolgte eine molekulargenetische Analyse zum Nachweis der Faktor-V-Leiden-Mutation und der Faktor-II-G20210 A-Mutation sowie eine serologische Untersuchung auf Antiphospholipid-Autoantikorper. Das Kontrollkollektiv bestand aus 20 gesunden Probandinnen ohne Abortanamnese mit mindestens einer unkomplizierten Schwangerschaft. Ergebnisse: Die Pravalenz der untersuchten Gerinnungsstorungen betrug 10 % (2/20 Patientinnen) im Studienkollektiv bzw. 15 % (3/20 Patientinnen) im Kontrollkollektiv. Fur keinen der plasmatischen Gerinnungsparameter konnte ein signifikanter Unterschied zwischen der Studien- und der Kontrollgruppe nachgewiesen werden. Beim Nachweis von Faktor-II- oder Faktor-V-Mutationen zeigte sich kein gehauftes Auftreten in einem der beiden untersuchten Kollektive. Ein Einfluss des Antiphospholipid-Autoantikorper-Status auf die Pravalenz hereditarer Gerinnungsstorungen konnte nicht beobachtet werden. Schlussfolgerung: Basierend auf diesen Ergebnissen erscheint der Nutzen eines gezielten Screenings auf hereditare Gerinnungsstorungen einschlieslich molekulargenetischer Techniken bei Patientinnen mit habitueller Abortneigung ohne positive Familienanamnese fragwurdig. Purpose: This study was undertaken to evaluate the incidence of haemostatic abnormalities and hypercoagulation mutations in women with a history of three or more consecutive spontaneous abortions and to investigate the influence of the antiphospholipid autoantibody status. Material and Methods: 20 non-pregnant habitual aborters were analysed for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen, protein S, protein C, antithrombin III, and antiphospholipid autoantibodies. Genetic analysis was performed to detect factor V Leiden mutation and factor II G20210A mutation. Twenty healthy non-pregnant multigravidae served as controls. Results: The incidence of haemostatic abnormalities or of factor II or V Leiden mutations did not differ significantly between women with a history of recurrent spontaneous abortion and controls. In 9 of 20 women with recurrent spontaneous abortions antiphospholipid autoantibodies (APA) were detectable. APA-positive and APA-negative study patients revealed similar results with respect to the investigated coagulation values Conclusion: According to our observations a general screening for hereditary coagulation disorders or hypercoagulation mutations should not be included in the routine work-up of women with a history of recurrent spontaneous abortions unless there is a history of familiar thrombophilia.

Objective: Leukaemia inhibitory factor (LIF) plays a central role in the control of implantation. We undertook this study to investigate the prevalence of LIF gene alterations in women with unexplained infertility and with recurrent failure of implantation after in vitro fertilisation (IVF) and embryo transfer. Patients and Methods: Forty five women with recurrent failure of implantation after IVF (group A), 50 with unexplained infertility (group B) and 105 fertile women (controls) were screened for LIF gene mutations. Standard genomic DNA extraction, PCR amplification of the LIF gene and single-strand conformation polymorphism (SSCP) analysis were used to search for mutations which were subsequently confirmed by DNA sequencing. Results: In group A, one woman was identified as having a neutral LIF gene polymorphism in exon 3 without affecting protein conformation. In group B, one woman with a heterozygous mutation and one with a neutral polymorphism were detected. In controls, only one woman with a neutral polymorphism in the intron between exons 2 and 3 was found. The woman with a potentially functional LIF gene mutation in group B achieved an ongoing clinical pregnancy after ovarian superovulation. Discussion: Potentially functional mutations in the LIF gene do unfrequently occur in women with unexplained infertility and may play a role in the etiology of infertility. However, routine screening for LIF mutations or polymorphisms in these women is not justified for the low prevalence of gene alterations.

Aufgrund der verbesserten Kulturtechnik durch den Einsatz sequenzieller Medien ist es heute moglich, Embryonen 5 Tage nach Eizellgewinnung im Blastozystenstadium zu transferieren, was die Selektion von Embryonen mit einer guten Implantationschance erlaubt. In Deutschland muss die Auswahl der zu transferierenden Embryonen bereits im Pronukleusstadium getroffen werden. Das Deutsche Embryonenschutzgesetz verbietet die Kultur von mehr als 3 Embryonen. Es durfen nur so viele Embryonen kultiviert werden, wie auch wieder ubertragen werden sollen. Das bedeutet, dass bereits im Pronukleusstadium die Embryonen identifiziert werden mussen, die ein hohes Potenzial fur eine erfolgreiche Implantation besitzen. Da dies nur unzureichend moglich ist, ist in Deutschland keine hohere Implantationsrate als 10–15% pro Embryo zu erwarten. Die Implantationsraten nach Blastozystenkultur erreichen dagegen bis zu 50%. Eine hohe Schwangerschaftsrate kann jedoch nur erzielt werden, wenn mehrere Oozyten bzw. Zygoten vorhanden sind, aus denen in einem spateren Entwicklungsstadium eine Selektion moglich ist. Durch das hohe Implantationspotenzial von Blastozysten werden weniger Embryonen fur den Transfer benotigt, was die Inzidenz von Mehrlingsschwangerschaften erniedrigt. Unter deutschen Bedingungen vermag die Blastozystenkultur im Vergleich mit der konventionellen Kultur bis zum Tag 2 oder 3 die Schwangerschaftszahlen nicht zu steigern.

Die pramature Ovarialinsuffizienz bezeichnet das Erloschen der Ovarialfunktion vor Erreichen des 40. Lebensjahres. Die Grunde hierfur sind heterogen und im individuellen Fall haufig nicht sicher zu klaren. An einem Climacterium praecox leiden etwa 1% aller Frauen unter 40 Jahren und ca. 0,3% der Frauen unter 35 Jahren. Die ovarielle Reserve lasst sich durch verschiedene Laboruntersuchungen und Funktionstests (Bestimmung von FSH am Tag 3, Inhibin B, Clomiphencitrattest, Gonadotrophin-Releasing-Hormon- (GnRH)-Stimulationstest) bestimmen. Damit einher geht ein schlechtes Ansprechen der Ovarien bei der exogenen Zufuhr von Gonadotropinen. "Lowresponder" sind definiert als Zyklen oder Patientinnen, in denen oder bei denen sich trotz hoch dosierter Gonadotropinbehandlung im In-vitro-Fertilisations- (IVF-) bzw. im intrazytoplasmatischen Spermieninjektions- (ICSI-)Programm weniger als 4 Eizellen gewinnen lassen. Die bislang publizierten Studien, die den Zeitpunkt des Eintritts der Menopause nach einem Stimulationszyklus mit schlechtem Ansprechen untersucht haben, zeigen, dass es bei fast allen Frauen innerhalb kurzer Zeit zu einem progressiven ovariellen Funktionsverlust kommt und die Menopause fruher als in einer Kontrollgruppe eintritt. Ein "Low-responder-Zyklus" kann somit als das erstes Anzeichen einer beginnenden Ovarialinsuffizienz interpretiert werden.

OBJECTIVE The success of artificial reproductive techniques not only depends on the quality of oocytes and spermatozoa but also on the receptivity of the endometrium. The aim of this study was to assess the role of endometrial volume measurement by three-dimensional ultrasound in predicting the pregnancy rate (PR) in women receiving controlled ovarian hyperstimulation followed by intrauterine insemination. MATERIAL AND METHODS 104 patients having intrauterine insemination (IUI) were included in this prospective trial. Ovarian hyperstimulation was performed with gonadotropins in 73 % of patients and with clomiphene citrate (CC) in 27 % of patients. Endometrial thickness, pattern and three-dimensional volume were measured immediately before insemination. RESULTS In 104 IUI cycles a total of 14 clinical pregnancies were recorded (PR=13.5 %). The endometrial volume was 3.5 ml and was not significantly different in pregnant (4.0 +/- 1.5 ml) from non-pregnant women (3.4 +/- 1.9 ml). In the subgroup of women with an endometrial volume > or = 2 ml and trilaminar endometrium the pregnancy rate was 22 %, significantly higher than that in women without these two criteria (PR 6 %, p < 0.05). The negative predictive value of an endometrial volume < 2 ml for a clinical pregnancy after IUI was 96 %. Endometrial volume and thickness were significantly higher after ovarian hyperstimulation with gonadotropins (3.7 ml and 11.0 mm) than with CC (2.8 ml and 9.5 mm; p < 0.05). CONCLUSIONS An endometrial volume < 2 ml at the day of insemination is associated with a poor likelihood of pregnancy. Endometrial volume measured by 3D ultrasound is a new objective parameter to predict endometrial receptivity.

OBJECTIVE Due to the improvements in human embryo culture in the recent years, it is now possible to transfer embryos five days after oocyte retrieval and IVF or ICSI at the blastocyst stage with favorable implantation rates. In Germany it is illegal to cultivate more than 3 embryos, therefore the selection has to be done at the pronuclear stage. There we report our experiences of human blastocyst culture in a routine IVF/ICSI programme under the conditions of the German Embryo Protection Law. MATERIALS AND METHODS The data of 100 couples undergoing the IVF-ICSI programme at the University Clinic of Wurzburg were analysed prospectively. 14-18 hours after insemination or micro-injection two or three zygotes with the best pronuclear development were selected for further cultivation. Fertilized oocytes were cultured in sequential media and were then transferred into the uterus 5 days after oocyte recovery. The blastocysts were graded from 1-8. RESULTS In 100 cycles a total of 859 oocytes were collected, of whom 663 were fertilized and reached the pronuclear stage (median fertilization rate 88.9 %). 251 zygotes were selected at the PN stage. 51 % of the selected zygotes achieved the blastocyst stage after 5 days (grade 1-5), 28 % were morulae (grade 6-7) and 21 % of the embryos arrested in their development (grade 8). The clinical pregnancy rate was 26 %. Women who conceived had a significant better development of blastocysts on day 5 (grade 4 versus grade 6, P < 0.01) than those not achieving pregnancy. CONCLUSIONS In summary, under the current legal conditions in Germany, blastocyst culture cannot improve pregnancy rates as the rate of arrested embryos of over 20 % limits the chances of implantation.

We report a 24-year-old woman with active acromegaly despite pituitary surgery and irradiation who received continuous octreotide LAR treatment for the control of GH excess throughout her pregnancy. The patient delivered a healthy girl following an uneventful pregnancy. Despite a substantial materno-fetal transfer of octreotide, postnatal development was normal with length parameters around the 50th percentile at 3 months of age. In almost all previously described cases (n = 13) octreotide was stopped after the diagnosis of pregnancy was established. No side-effects of mother or fetus have been reported. Octreotide treatment in pregnancy seems to be feasible and safe. Due to the still-limited number of reported cases, the potential benefits of octreotide treatment should be weighed carefully against its possible risks.

Im Gegensatz zu Frauen mit ausgetragenen Schwangerschaften finden sich bei Frauen mit wiederholten Aborten typische Veranderungen des zellularen und humoralen Immunsystems, die in erster Linie das uterine Kompartiment betreffen, jedoch in der peripheren Zirkulation nur zum Teil nachweisbar sind. Manche dieser Phanomene sind wahrscheinlich kausal am ungunstigen Ausgang der Schwangerschaft beteiligt, andere durften auf eine veranderte endokrine und parakrine Regulation im Verlauf des Abortgeschehens zuruckzufuhren sein. Zum Zeitpunkt der Implantation, in der Lutealphase des Konzeptionszyklus, findet man bei Frauen mit wiederholten Aborten, im Vergleich zu fertilen Frauen ohne Aborte, eine veranderte Population von Lymphozyten im Endometrium, eine erhohte Zahl und Aktivitat von CD16 + CD56 + -naturlichen Killerzellen (NK) und eine Verschiebung der von den T-Helferzellen (Th) produzierten Zytokine in Richtung der inflammatorischen Th-1-Zytokine (IL-2, IL-12, Interferon-γ). In der peripheren Zirkulation ist zum Zeitpunkt der Konzeption ebenfalls die Aktivitat der NK-Zellen und die Produktion von Th-1-Zytokinen durch T-Effektorzellen erhoht. Organspezifische, nichtorganspezifische und gerinnungsaktive Antikorper weisen auf eine generelle Aktivierung des humoralen Immunsystems hin. Zum Zeitpunkt eines erneuten Abortes ist die Tiefe der Trophoblastinvasion in das Myometrium meist ungenugend. Die Implantationsstelle enthalt eine erhohte Zahl von NK-Zellen, und die Produktion der antiinflammatorischen und protektiven Th-2-Zytokine (z. B. LIF, IL-4, IL-10) durch deziduale T-Zellen ist reduziert. Die genannten Phanomene sind zum Teil durch Immunisierung mit allogenen Lymphozyten, Gabe von Immunglobulinen oder Medikamente (Acetylsalicylsaure, Heparin, Prednison) therapeutisch beeinflussbar.

Objective: Myomas can be associated with an increased rate of spontaneous pregnancy loss, premature delivery, and placental insufficiency. Indications for surgery include complications, rapid growth, infertility, and early pregnancy loss. We evaluated pregnancy outcome in patients after myomectomy Methods: We reviewed pregnancy outcomes in all 77 patients who underwent myomectomy between 1993 and 1997 Myo mectomy was performed via laparotomy in 42 women, laparo scopically in 24, hysteroscopically in 9, and at cesarean section in 2 women Results: 49 of the 77 patients attempted to become pregnant after myomectomy and 20 (41%) conceived by 1999. The pregnancy rate was inversely associated with the number of myomas removed. Of the 28 patients in whom a single myoma was removed, 15 (54%) became pregnant as compared with 2 of the 11 (18%) with removal of more than two fibroids (p = 0.004). There was no association between the pregnancy rate and the size of the removed myomas. Seven of 13 patients after laparoscopic myomectomy became pregnant compared with 11 of 30 after open surgery. Twenty patients had a total of 35 pregnancies, Nine patients had 16 pregnancies with complications (4 with spontaneous abortion, 4 with preterm delivery, 3 with premature rupture of the membranes, 2 with failure to progress, 2 with intrauterine growth restriction, 1 with placental abruption). Fifteen patients (79%) were delivered vaginally. There was no case of uterine rupture. 75% of the patients delivered by cesarean section had intramural myomas. Conclusion: Myomectomy should be considered in womer with myomas who wish to become pregnant, particularly if the myomas are large or multiple. The surgical approach will depend on the location, number and size of the myomas.

Endocrine evaluation as a prerequisite for every patient undergoing routine in-vitro fertilization (IVF) and embryo transfer for tubal or male factor infertility is still a matter of debate. The aim of this study was to determine if a full endocrine work-up, including the measurement of androgens, gonadotropins, prolactin and TSH, is conclusive for the subsequent success in IVF/ET. 71 infertile women without known endocrinopathies (e.g., polycystic ovarian disease), who were scheduled to enter the IVF/ET program were studied under strictly standardized conditions during the follicular phase of a natural cycle. Fasting serum concentrations of follicle stimulating hormone, luteinizing hormone, oestradiol, progesterone, prolactin, testosterone (T), dehydroepiandrosterone, 17-OH-progesterone, androstenedione and thyroid stimulating hormone (TSH) were measured using commercially available radioimmunoassays. Ovarian stimulation was performed by a long gonadotrophin-releasing hormone agonist/human menopausal gonadotrophin protocol. The overall clinical pregnancy rate was 15.5% in the first started IVF cycle. While patients who conceived in the first treatment cycle had significantly lower T levels (368±49 pg/ml) than those who did not (518±27 pg/ml, p=0.042, Kruskal & Wallis H-test), but the percentage of women with elevated T concentrations was not different. Similarly, TSH concentrations were significantly higher in women with a clinical pregnancy (1.9±0.2 mU/ml) than in non-pregnant women (1.4±0.3 mU/ml, p=0.046), but levels were still within the normal range. There were no further significant differences in hormone levels between pregnant and non-pregnant patients. These results do not suggest the measurement of a full hormonal profile in all infertile women before IVF/ET in non-endocrine infertility, taking into account the low likelihood to identify endocrinological disturbances, the considerable cost of endocrine testing and the paucity of therapeutic consequences

BACKGROUND Two different methods are in use for induction of abortion: either dilation and curettage (D & C) or medical termination with antigestagens and/or prostaglandins. The risk of continuing pregnancy after D & C ranges from 0.023 to 1% and is inversely correlated with gestational age. METHODS AND RESULTS Several authors reported fetal anomalies (limb and oro-facial defects) in such cases. For the medical induction of abortion a combination of Mifepristone and Misoprostole is the treatment of choice in order to reduce the risk of ongoing pregnancy. Using single drug therapy carries an increased risk of failure and of subsequent fetal anomaly. There seems to be an increased incidence of limb defects and Mobius' syndrome in fetuses born after failed termination of pregnancy, but normal fetal development is entirely possible. CONCLUSION/DISCUSSION The patients concerned must be informed in detail of the risks and probable consequences which must be included in the counselling concept of the treating gynaecologist.

Objective: To compare maternal and umbilical venous big endothelin (big ET) and endothelin-1 (ET-1) levels of pregnancies complicated by severe preeclampsia (PE) or HELLP-syndrome to those of a well-matched normotensive pregnant control group. Methods: We measured plasma levels of ET-1 and big ET in 16 patients with severe PE and 14 patients with HELLP-syndrome by commercially available RIAs and compared them with those of well-matched normotensive pregnant controls. Additionally, the umbilical venous ET-1 and big ET levels were determined in 10 corresponding newborns. Results: The plasma concentrations of ET-1 and big ET were significantly higher in patients with severe PE and especially in women with HELLP-syndrome when compared with controls. The molar ratios of big ET to ET-1 were significantly lower in the two study groups. The levels of ET-1 and big ET were higher in umbilical venous plasma than in maternal plasma, but there were no significant differences in the umbilical venous concentrations between normotensive and by severe PE or HELLP-syndrome complicated pregnancies. Conclusions: These findings suggest that ET-1 may be considered as a marker of endothelial injury in by severe preeclampsia or HELLP-syndrome complicated pregnancies. The increase of the ET-1 plasma levels may be due, at least in part, to changes in the conversion of big ET to ET-1 by the endothelin-converting enzyme.

A prospective, randomized, double-blind and placebo-controlled study was conducted to assess the effectiveness of i.v. administration of 6% hydroxyethyle starch solution (HES) in preventing moderate and severe ovarian hyperstimulation syndrome (OHSS) in patients in an in-vitro fertilization programme. A total of 101 women who had serum oestradiol concentrations >1500 pg/ml and/or more than 10 follicles on day of human chorionic gonadotrophin (HCG) administration were recruited into two groups: HES group (n = 51) received 1000 ml 6% HES; and the placebo group (n = 50) received 1000 ml of sodium chloride 0.9% solution at the time shortly after embryo transfer. Follow-up examinations 7 +/- 1 and 14 +/- 1 days after embryo transfer included transvaginal ultrasound (diameters of each ovary and maximum cysts, number of cysts, ascites), blood tests (serum oestradiol, progesterone, beta-HCG, C-reactive protein, blood count, plasma proteins, electrolytes, kidney function tests) and evaluation of abdominal pain, nausea, diarrhoea, abdominal swelling and weight gain. Only one moderate OHSS developed in the HES group whereas seven moderate-severe cases were observed in the placebo group (P = 0.031). Furthermore, serum oestradiol concentration, leukocyte count, increase in abdominal circumference and weight gain 14 days after embryo transfer were significantly higher in the placebo group. There were no differences between the two groups in terms of age, oestradiol concentration and number of follicles at time of HCG injection. Administration of 6% HES prevents the development of moderate-severe OHSS in risk patients.

Background. To investigate plasma renin activity and aldosterone serum concentrations in severe preeclampsia (PE) or HELLP-syndrome.Methods. We measured plasma renin activity and serum concentrations of aldosterone, progesterone, estradiol and estriol in 16 patients with PE and 14 patients with HELLP-syndrome and in well-matched normotensive pregnant controls. Additionally, the umbilical venous levels of aldosterone and plasma renin activity were determined in ten corresponding newborns.Results. Serum aldosterone levels as well as plasma renin activity were significantly lower in patients with PE but not in women with HELLP-syndrome when compared to controls. We did not find any relationship either between aldosterone serum concentration or plasma renin activity and progesterone, estradiol or estriol levels in PE or in the HELLP-syndrome. Umbilical venous renin activity and aldosterone levels were higher than in maternal blood, but there were no significant differences in the umbilical venous levels betwe...

Im Rahmen der Implantation und der Ausbildung der fruhen Plazenta nimmt das dezidualisierte Endometrium (Dezidua) zwangslaufig eine zentrale Rolle ein, da es an diesem anatomischen Ort zu einer Infiltration durch invasive Zytotrophoblastzellen embryonaler Herkunft kommt. Da dieser Vorgang in der Regel zeitlich und raumlich kontrolliert verlauft, stellt sich – insbesondere bei pathologisch verlaufenden Schwangerschaften – die Frage nach der Beteiligung des mutterlichem Immunsystems an dieser Regulation. In der folgenden Ubersicht wird der aktuelle Erkenntnisstand uber die Rolle von zellularen und humoralen Immunvorgangen im Rahmen der Dezidualisation und der fruhen Ausbildung der Plazenta zusammengefast. Daruber hinaus werden die bislang publizierten Daten zu pathologischen Schwangerschaftsverlaufen als mogliche Folge von immunologischen Fehlregulationen im Rahmen der Plazentation kritisch diskutiert.

Therapeutic options for postoperative vaginal bleeding usually comprise conservative management and active intervention, such as vaginal-uterine packing, vaginal suture-ligation of the bleeding source, laparotomy ligation of uterine vessels and/or hysterectomy. Selective angiographic embolization of the internal iliac arteries has emerged as an alternative to surgery to avoid relaparatomy. We report on a patient who underwent emergency arterial catheterisation due to intractable genital tract bleeding after vaginal hysterectomy. The bleeding site could be angiographically identified as branches of the internal iliac artery. Bleeding was successfully treated after embolisation of the leaking vessel with platinum coils.

The purpose of this study was to compare peripartum maternal and umbilical cord serum serotonin levels in singleton pregnancies complicated by the HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) or by severe preeclampsia with those of appropriate controls. The study population comprised 14 primigravidae women with class 1 or 2 HELLP syndrome (platelet count50,000 or100,000/mm3, elevated transaminase levels, evidence of hemolysis) and 17 women with severe preeclampsia (American College of Obstetricians and Gynecologists criteria). Serotonin was measured in maternal serum immediately before delivery and in umbilical cord serum by a highly sensitive 125I-radioimmunoassay. The control groups comprised 31 women who had uncomplicated deliveries at term (control group I) and another 31 at the gestational age matched to that of each patient (control group II). Maternal serum serotonin concentration was 59.5 +/- 36.1 ng/ml (mean +/- SD) in the HELLP group, versus 94.9 +/- 40.5 ng/ml in control group I (p = 0.043, U-test) and 88.7 +/- 29.4 ng/ml in control group II (p = 0.048). Levels in the preeclampsia group (51.6 +/- 32.2 ng/ml) were not different from those in the HELLP group but were equally decreased when compared to control groups I (p = 0.009) and II (p = 0.003). We have observed a similar depression of serum serotonin concentrations both in severe preeclampsia and in the HELLP syndrome, reflecting the decreased platelet content of serotonin. It is uncertain whether these changes may be causally involved in the pathogenesis of hypertensive disorders of pregnancy. Decreased serum serotonin concentration may serve as an additional marker for platelet activation in preeclampsia and in the HELLP syndrome.

The aim of our study was to evaluate pretreatment semen quality in patients with unilateral testicular cancer in comparison to semen parameters of patients suffering from other malignancies.Semen analysis according to WHO recommendations were performed in 16 patients suffering from unilateral testicular cancer (group 1) and in 21 patients who were diagnosed to have other malignant tumors (group 2: non-Hodgkin's lymphoma: n=7, Hodgkin's disease: n=6, leukemia: n=3, osteosarcoma: n=2, rectal cancer: n=2, thyroid carcinoma: n=1) prior to anti-cancer treatment.Normozoospermia was observed in none of the testicular cancer patients but in five of the other patients ( p=0.047). Sperm concentration was significantly decreased in the patients of group 1 compared to those of group 2 (18.7+/-22.3x10(6)/ml versus 35.6+/-31.3x10(6)/ml, p=0.03). The percentage of rapid progressive motile spermatozoa was significantly less in testicular cancer patients than in patients suffering from other malignancies (WHO group a: 1.1+/-2.0% versus 4.7+/-5.6%, p=0.02). Normal morphological findings of spermatozoa were found in a smaller percentage in group 1 (16.2+/-6.0% versus 26.1+/-18.0%, p=0.03).Our investigations revealed that especially testicular cancer has an adverse influence on sperm quality. Hence, we advise careful and sufficient cryopreservation of semen in those patients taking the negative impact of cytotoxic treatments on semen parameters into account.

A 36-year-old G4P1 presented at 20 weeks gestation with vaginal bleeding. Her obstetrical history was significant for two first-trimester spontaneous abortions requiring curettage and a cesarean section. On admission placenta praevia was suspected by ultrasound. A placenta percreta was suspected by ultrasound follow-up at 30 weeks. At 33 weeks she underwent cesarean section because of serious vaginal bleeding. The profound blood loss with consecutive coagulopathy required an emergency hysterectomy and multiple blood transfusions. Placenta percreta is a rare but dramatic complication after previous cesarean section. This should be kept in mind as the rate of elective cesarean sections is rising continuously.

Background Geniculate neuralgia, although uncommon, can be a debilitating pathology. Unfortunately, a thorough review of this pain syndrome and the clinical anatomy, function, and pathology of its most commonly associated nerve, the nervus intermedius, is lacking in the literature. Therefore, the present study aimed to further elucidate the diagnosis of this pain syndrome and its surgical treatment based on a review of the literature. Methods Using standard search engines, the literature was evaluated for germane reports regarding the nervus intermedius and associated pathology. A summary of this body of literature is presented. Results Since 1968, only approximately 50 peer-reviewed reports have been published regarding the nervus intermedius. Most of these are single-case reports and in reference to geniculate neuralgia. No report was a review of the literature. Conclusions Neuralgia involving the nervus intermedius is uncommon, but when present, can be life altering. Microvascular decompression may be effective as a treatment. Along its cisternal course, the nerve may be difficult to distinguish from the facial nerve. Based on case reports and small series, long-term pain control can be seen after nerve sectioning or microvascular decompression, but no prospective studies exist. Such studies are now necessary to shed light on the efficacy of surgical treatment of nervus intermedius neuralgia.

Wir verglichen die Sensitivitat und diagnostische Prazision des freien Androgenindexes (FAI) mit den von Gesamttestosteron (T), freiem Testosteron (fT), Androstendion (A), LH und der Ratio LH/FSH von

Spontaneous migration of a radionuclide tracer from the vagina to the peritoneum may be visualized by scintigraphic imaging (hysterosalpingoscintigraphy, HSS). A prospective study was designed to evaluate diagnostic criteria for normal tubal passage of a control group (n = 7) and to establish the predictive value of the HSS technique in defining functional deficiency in anatomically patent tubes. In 56 patients with tubal and unexplained infertility, a comparison between the results of the tracer migration study and of contrast hysterosalpingography and laparoscopy was made. The overall correlation was 65%. Clearly discrepant results (i.e. an abnormal migration pattern in anatomically patent tubes) were recorded in 18% and were positively, yet not significantly associated with tubal adhesive disease and with a history of tubal microsurgery. Interpretation of scans was equivocal in another 18% of patients due to undetectable ascension of the tracer to the uterus. It is suggested that the radionuclide is moved forward by the same passive transport processes which are concerned with support of the migration of spermatozoa to the ovum, and that failure of tubal migration of the tracer may render patients eligible for in-vitro fertilization/embryo transfer treatment.

We report the case of a primipara who delivered healthy twins vaginally at term with a time interval between twins of 9 h and 19 min. Neonatal outcome and further development were normal in both twins.

We report on a case where late intracytoplasmic sperm injection (ICSI) on unfertilized oocytes after standard in-vitro fertilization (IVF) cycles resulted in a dizygotic twin pregnancy. Fifteen oocytes were harvested from a patient with a history of salpingotomy. After a single cycle of IVF, only one oocyte showed two pronuclei. Subsequently ICSI was performed on six unfertilized metaphase II oocytes, and three of these oocytes showed two pronuclei. Three fertilized embryos were transferred (two derived from ICSI and one from IVF). A normal twin pregnancy resulted, and after delivery of two healthy boys the twins were confirmed to be dizygotic by DNA analysis of several loci. We conclude that at least one of the embryos was derived from the reinsemination by 'second day ICSI'.

Objective: Dendritic cells (DC) play a central role in initiating and polarizing immune responses. As effects of pregnancy associated hormones on phenotype and function of DC are unknown, our objective was to test the influence of progesterone, β-estradiol and βHCG on immature (iDC) and mature (mDC) DC. Study design: DC generated from peripheral-blood-monocytes were exposed to different doses of hormones. DC phenotype was determined by FACS-analysis of surface marker expression (CD40, CD86, CD83 and HLA-DR). Modifications in the secretion of cytokines (IL12p70, IL-18, IL-10, IL-6, TNFα) and chemokines (MDC, IL-8) were analysed by ELISA. T cell stimulatory capacity of mDC was assessed by mixed lymphocyte reaction. Results: Incubation with progesterone or estradiol resulted in a significant upregulation of IL-10 production by iDC and mDC. Combinations of progesterone and βHCG or estradiol respectively induced a significant decrease in production of IL-18 by mDC. No significant changes could be observed in surface marker expression or T cell stimulatory capacity, neither in cultures of DC matured under influence of progesterone, estradiol nor βHCG. Conclusions: PBMC-derived DC seem to be relatively stable against the influence of pregnancy associated hormones apart from particular effects on cytokine production which partly could contribute to the modification of immune responses observed in normal early pregnancy.

Objective : The effects of modern oral contraceptives (OC) on serum concentrations of folate and cobalamin are controversial. Study design : Case-control study on the cobalamin and folate status of 71 healthy female nulligravidae using "low dose" OC for ≥3 months and 170 controls. Factors interfering with vitamin metabolism were thoroughly controlled. Serum concentrations were measured by commercial assays. The results were evaluated using Mann–Whitney's U -test and χ 2 analysis. Results : OC-users showed significantly lower concentrations of cobalamin than controls. The rates of women with reduced, normal, and elevated levels differed significantly. Nine users but no control had frank cobalamin deficiency without clinical symptoms. Folate levels did not differ between the groups. Vegetarian diet, smoking or obesity did not have a significant influence. Conclusions : Routine measurement of cobalamin or folate in women using "low dose" OC is not warranted. Vitamin supplementation or different contraceptive methods should be considered in women with pre-existing cobalamin deficiency or restrictive dietary habits.

A 27-year-old woman with a periodically bleeding out of the umbilicus was found to have umbilical endometriosis. She was never pregnant before and had no pelvic surgery. The umbilical lesion was excised following a diagnostic laparoscopy revealing extragenital endometriosis. Umbilical endometriosis is a very rare disease, but should be considered in the differential diagnosis of umbilical lesions.

This study was undertaken to evaluate whether the presence of thyroid antibodies in euthyroid women is associated with an adverse outcome in an in-vitro fertilization (IVF)-embryo transfer programme. In 24 women (study group: mean age +/- SD: 31.5 +/- 4.4 years) who failed to conceive after having three or more cycles of IVF and embryo transfer, serum concentrations of thyroglobulin (TG), thyroid peroxidase antibodies (TPO) and anticardiolipin antibodies (IgG and IgM) were measured using commercially available kits. The control group comprised 24 consecutive patients without endocrine dysfunction (mean age +/- SD: 30.3 +/- 4.1 years) seeking infertility treatment in our department of assisted reproduction. All patients in both the study and the control groups were determined to be euthyroid by demonstrating normal concentrations of thyroid-stimulating hormone (TSH). In the study and control groups respectively, 13 and two patients demonstrated positive titres of TG, TPO or both thyroid antibodies (Fisher's exact test: P = 0.002). Mean serum concentrations of TG were significantly increased in the study group compared to the control subjects (156 +/- 167 IU/ml versus 33.5 +/- 32.0 IU/ml; U-test: P = 0.009). Serum concentrations of TPO and anticardiolipin antibodies were similar in both groups. Our investigations revealed that thyroid antibodies might be independent markers for reproductive failure in an IVF-embryo transfer programme.

The study was conducted to identify medical, obstetrical and social risk factors associated with early preterm births (32+0 gestational weeks).The Statewide Perinatal Survey of Bavaria is a collection of perinatal data from all Bavarian maternity units using a uniform numbered questionnaire. Data on 106345 singleton births from the 1994 Survey were analysed using univariate and multivariate logistic regression analysis.In the multivariate analysis, early preterm birth was associated with premature rupture of the membranes (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.37-1.86), treatment for infertility (OR 1.7, 95% CI 1.19-2.34), previous induced abortion (OR 1.8, 95% CI 1.57-2.13), maternal age35 years (OR 1.8, 95% CI 1.47-2.16), premature cervical dilatation (OR 2.3, 95% CI 1.86-2.94), a history of stillbirth (OR 3.2, 95% CI 2.13-4.83), a history of preterm birth (OR 3.3, 95% CI 2.45-4.48), maternal age18 years (OR 3.4, 95% CI 2.03-5.61), malpresentation (OR 3.9, 95% CI 3.10-4.93), preeclampsia (OR 4.0, 95% CI 3.20-4.94), uterine bleeding (OR 5.0, 95% CI 4.08-6.02), preterm labour (OR 7.0, 95% CI 5.94-8.22), and chorioamnionitis (OR 22.3, 95% CI 17.40-28.66).These data identify a subgroup of women at an increased risk for early preterm birth and may benefit from an intensified prenatal care. Risk factors related to the obstetrical history, genital infections, preeclampsia and maternal age are the most relevant for early preterm birth.

A retrospective analysis was made on the singleton births included in the Bavarian statewide perinatal registry (Bayerische Perinatalerhebung, BPE; 99,252 births from BPE 1987 and 79,661 births from BPE 1988) with respect to the timing of the first prenatal consultation and the frequency of visits during pregnancy. If the first prenatal visit was scheduled after 21 weeks, the rates of infants transferred to pediatric units relative risk (RR = 1.34, P0.0001, chi 2-test), of low birth weight (RR = 1.41, P0.0001) and of stillbirths (RR = 1.70, P0.025) were higher than if the first visit was at 9-12 weeks. Similarly, after4 prenatal visits, the rates of infants transferred (RR = 3.91), of low birth weight (RR = 9.18), of stillbirths (RR = 7.65) and of neonatal deaths (RR = 29.5) were significantly (P0.0001) higher than after10 visits. Prenatal care was defined as 'standard' if the initial consultation was scheduled at or before 12 weeks and whether 10-12 visits were completed during a normal duration of pregnancy. 'Below standard' prenatal care was associated with a higher rate of infants transferred (P0.01) and of stillbirths (P0.0005). Prenatal care was more frequently (P0.0001) classified as 'below standard' in mothers older than 39 years (40.45%, RR = 2.45) and in adolescent mothers (58.67%, RR = 5.12) than in those 25-29 years of age (21.71%), in fourth and subsequent (48.22%, RR = 3.44) than in first pregnancies (21.32%) and in foreign (39.65%, RR = 2.18) than in German mothers (23.19%).(ABSTRACT TRUNCATED AT 250 WORDS)

We report a case of repeated fetal death at 31 gestational weeks associated with mild non-proteinuric pre-eclampsia and intrauterine growth retardation. After double intradermal immunisation with paternal leukocytes, a third pregnancy proceeded uneventfully until it ended at 38 weeks. Maternal anti-paternal blocking antibody activity was assessed by the erythrocyte antibody inhibition (EAI) test. Serologic testing revealed that the couple did not share HLA class I antigens. The mechanisms underlying the likely benefit from immunotherapy are discussed.

5030 Background: Topotecan combined with etoposide (GINECO 1998) and gemcitabine (NOGGO 2001) proved effective for second-line treatment of recurrent ovarian cancer. It is, however, unclear whether combined treatment improves survival and tumor control compared to topotecan alone. Methods: Women with recurrent ovarian cancer after primary surgery and platinum therapy were enrolled in an open-label randomized phase-III trial at 93 German institutions. Stratifying for treatment-free intervals (TFI) of less or more than 12 months, subjects were centrally allocated to topotecan 1.25 mg/m2/d (TM), topotecan 1.0 mg/m2/d plus oral etoposide 50 mg/d (TE) on day 6–12, or topotecan 0.5 mg/m2/d plus gemcitabine (TG) 800 mg/m2/d1 and 600 mg/m2/d8 every three weeks. Local institutional review boards approved this study, and all patients provided written informed consent. With 145 subjects each arm, this study yielded 90% power to detect a Hazard Ratio (HR) of 0.60 in overall survival (OS) at a two-sided alpha of 0.01. We employed Cox regression for primary endpoint analysis, and addressed progression-free survival (PFS) and toxicity descriptively. Results: Between September 1999 and November 2004, 3036 courses were administered to 505 patients (mean age 60.4 [SD 11.3] years), 208 of whom had a TFI No significant financial relationships to disclose.

5089 Background: Despite of the effectiveness of radical surgery and first-line chemotherapy, most patients (pts) with advanced ovarian cancer will relapse. Paclitaxel (P) in combination with C as second-line treatment improves the outcome of pts with platinum-sensitive ROC in comparison to C monotherapy. Due to polyneuropathy and alopecia this regimen can not be offered to all pts. Therefore, other platinum-combinations are required. We conducted a phase I/II study to define the dose limiting toxicities (DLT) and the tolerability of combination therapy with T and C. Methods: Pts with platinum-sensitive ROC and primary standard therapy were stratified according to treatment-free interval (TFI): 6–12 months (A) and ≥12 months (B). Following dose regimens were analysed: T 1mg/m2/d1–3 + C AUC5/d3 and T 0.75 mg/m2/d1–3 + C AUC5/d3, q21d. DLT was based on the first 4 courses and defined as: CTC grade 3/4 hematological and grade 2 non-hematological toxicity (excepted alopecia, vomiting), treatment delay >7d. Primary endpoints were DLT and tolerability. Secondary endpoints were remission rate (RR) and progression-free survival (PFS). Results: From 06/04 to 08/05, 28 pts were enrolled, 26 pts (A:13 pts, B:13 pts) were eligible. Median age was 61.5 years. A total of 141 cycles were analysed, median number of cycles was 6 (range A:2–8, B:1–10). DLTs were: leucopenia (n = 5) and thrombocytopenia (n = 1). MTD was reached at dose: T: 0.75mg/m2 and C: AUC5. Overall, grade 3/4 hematologic toxicities (in% of all cycles), for (A) and (B) respectively, were: anemia 4% vs. 4%, leucopenia 34% vs. 13%, neutropenia 30% vs. 31%, thrombocytopenia 7% vs. 6%. Febrile neutropenia 4.3% vs. 0%. Darbepoetin alfa was given in 13.5% of all cycles. Overall, grade 3/4 non-hematologic toxicities were infrequent (< 5%). Overall RR (95% CI) was 50% (29.7–70.1) [A: 30.8% (0.1–61.1), B: 69.3% (38.7–90.9)]. Median follow-up was 5.8 mo, median PFS (95% CI) was 7.7 mo (1.3–9.4) [A: 6.2 (1.3–7.2), B: 8.0 (7.3–9.4)]. Median overall survival was not reached. Conclusions: TC is a feasible and effective chemotherapy regimen for platinum sensitive ROC. Tolerability is not associated to TFI. The recommended dose for subsequent studies is T:0.75 and C:AUC5. No significant financial relationships to disclose.

8140 Background: Bone metastases in cancer patients may lead to severe bone pain, pathological fractures, and hypercalcemia. The development of osteolytic destruction is due to activation of osteoc...