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Background: Routine use of multigene RT-PCR based assays as Recurrence Score (RS) vs. single markers (grade, uPA/PAI-1, HR, HER2, Ki-67) is controversially discussed in early BC. Several definitions of luminal A/B subtypes have been proposed by St. Gallen guidelines and individual researchers (grade 1/2 vs. 3, Ki-67 cut-offs 14 or 20%). Recently, integration of PR>20% was proposed as an immunhistochemical luminal A subtype definition (Ki-67 Methods: planB trial (04/09 to 11/11: n=2,449 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2− BC; n=3197 registered; n=3072 available for central tumor bank). RS was used as selection criterion for chemotherapy (CTx) omission in HR+ BC (if RS Results: RS distribution in 2569 HR+ tumors: 0–11 (18%), 12–25 (60%), >25 (22%) (RS1853%/34%/13%). Luminal A subtype based on Ki-67 cut-off of 20% was included in the luminal A/Ki-67 Luminal A/B based on local/central grade: 79%/21%; 67.9%/32.1%. In 354 pN0-1 patients, CTx was omitted based on low RS (88% compliance). In this group, 62% were high-risk by clinical-pathological criteria. Allocation to luminal A/B subtypes based on local/central grade varied substantially: overall concordance was 72%, but 40% of locally luminal B (HR+/G3) were luminal A (HR+/G1/2) by central and 60% of centrally luminal B were luminal A locally. Moderate correlations were found between RS and central grade (Spearman correlation rs=0.317; p < 0.001), local grade (0.321; p < 0.001) and Ki-67 (rs = 0.374; p < 0.001), particularly due to poor correlations in the RS group Inclusion of PR>20% moderately improved the correlation between luminal subtypes and RS to rs=0.34; p < 0.001. Data on allocation to luminal subtypes by local/central Ki-67 will be presented at the meeting. Conclusions: Our results represent the first prospective correlation of different luminal A/B definitions vs. a guideline mentioned gene signature (RS). High RS usually implies high grade and luminal B classification, the converse is not true. There is substantial heterogeneity in risk assessment by luminal A/B classification and grade in low/intermediate RS groups. Concordance for central/local assessment of grade and luminal A/B status was limited. There is strong need for standardization of molecular subtype's immunhistochemical/clinical definition prior to implementation into daily routine. Clinical significance of these findings will be addressed by further follow up of the WSG-planB trial. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-08.

Die Gruppe der sogenannten spaten Fruhgeborenen („Late preterm“- Kinder mit einem Gestationsalter von 340/7–366/7 Schwangerschaftswochen (SSW)) wird hinsichtlich ihres neonatologischen Outcomes unterschatzt. Bei vor der 29. SSW geborenen Kindern zeigte sich ein fur Madchen vorteilhafter geschlechtsspezifischer Unterschied bezuglich der Morbiditat. Ziel dieser Studie ist es, zu prufen ob diese Ergebnisse auf die Late preterm-Gruppe ubertragbar sind. Untersucht wurde das neonatale Outcome bei 528 konsekutiven intensivpflichtigen Einlingen des Gestationsalters 340/7–366/7 Wochen. Neonatologische Komplikationen wurden auf Geschlechtsspezifitat gepruft. Jungen (n=292) wiesen signifikant haufiger eine Sepsis (3,8 vs. 0,9%; p=0,0314, x 2-Test), Madchen signifikant langere Aufenthalte auf der neonatologischen Intensivstation auf (Median 12 (Q1:8; Q3:17) vs. 11 (6;16) Tage; p=0,0149, t-Test). Im multiplen logistischen Regressionsmodell zeigte sich eine grenzwertige Signifikanz fur das mannliche Geschlecht und fur vorzeitigen Blasensprung bezuglich des Auftretens einer Sepsis – ein 4,4-faches Risiko fur Jungen (OR=0,228 [95% CI: 0,050–1,041]; p=0,0564) und ein 3,5-faches Risiko fur vorzeitigen Blasensprung (OR=3,462 [0,938–12,779]; p=0,0623). Als starke Einflussgrosen fur die Aufenthaltsdauer auf der Intensivstation zeigten sich nach Adjustierung Geburtsgewicht, Gestationsalter und vorzeitiger Blasensprung. Der Einfluss des fetalen Geschlechtes auf das neonatologische Outcome hat sich in der Late preterm-Gruppe (340/7–366/7 SSW) relativiert.

Background: Anthracycline-taxane based adjuvant chemotherapy (cht) is considered standard in node-positive and high-risk node-negative BC. However, retrospective analyses suggest that in HER2−BC, benefit from anthracyclines may not outweigh acute and long term toxicities. Recurrence Score (RS) identifies patients who are not candidates for cht based on their low relapse risk, as well as minimal, if any, benefit of cht. The WSG Plan B trial investigates anthracycline-free cht in HER2− BC and is the first trial in Europe prospectively incorporating RS for decision making regarding adjuvant cht in both N0 and N+ BC. Methods: Plan B trial randomizes HER2− BC patients with high-risk N0 (at least one risk factor: ≥pT2; negative HR status; G2-3; age ≤35 years old; high uPA/PAI-1) or N+ disease to 6xTC (Docetaxel 75Cyclophosphomide600) vs. 4xEC (Epirubicin90Cyclophosphomide600)-4xDocetaxel100 G-CSF prophylaxis is recommended according to current ASCO guidelines. The statistical design previews n=2.448 randomized to cht; patients with HR+ BC, N0-3 and a RS ≤11 receive endocrine therapy only. Results: From April 2009 to June 2011, 3037 patients have been recruited and 2296 randomized (TC/EC-Doc: 1146/1150; age The most frequent SAEs were: leucopenia, febrile neutropenia (TC/EC-Doc:37 (3.3%)/31 (2.7%), n.s.), infections and heart/vascular events (TC/EC-Doc 29/40, n.s.). In patients ≥65 years old, there is a trend towards more febrile neutropenia (13 vs. 5; p=0.06) in the TC, and more severe mucositis/diarrhea/nausea (3 vs. 15; p=0.007) and heart/vascular events (5 vs. 14; p=0.06) in the EC-Doc arm. There were 5 therapy related deaths (TC 5 (0.4%)/EC-Doc 0, p=0.03); 3 in patients Detailed data on relationship between the protocol specified, RS-guided treatment assignment and toxicity, and use of G-CSF support will be updated for the meeting. Conclusions: The Plan-B trial is one of the largest randomized phase III trials currently evaluating anthracycline-free adjuvant cht in HER2− BC. The cht administered within the study was generally well tolerated, but higher number of treatment-related deaths has been observed within the TC arm. The short term toxicity profile seems be different between both study arms, particularly in patients >65 years old. On the basis of prognosis as determined by RS, cht has been spared after a shared decision process in a substantial group of patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-03.

Background The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of standard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer. Patients and methods A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of paclitaxel 175 mg/m2 every 3 weeks (EC→T), or three cycles of epirubicin 150 mg/m2 every 2 weeks followed by three cycles of paclitaxel 225 mg/m2 every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (Edd→Tdd→CMF). The patients were randomly assigned to receive darbepoetin or none. The primary objective was to demonstrate a superior disease-free survival (DFS) of Edd→Tdd→CMF compared with EC→T. Results Estimated 3-year DFS was 75.8% with EC→T versus 78.8% with Edd→Tdd→CMF [hazard ratio (HR) 1.14; P = 0.37] and overall survival (OS) 88.4% versus 91.5% (HR 1.26; P = 0.237). Three-year DFS was 74.3% with darbepoetin versus 80.0% without (HR 1.31; P = 0.061) and OS 88.0% versus 91.8% (HR 1.33; P = 0.139). Patients with a pathologically documented complete response [pathological complete response (pCR)] had a significantly better DFS compared with those without achieving a pCR (estimated 3-year DFS: 89.2% versus 74.9%; HR 2.27; P = 0.001). Conclusion Neoadjuvant dose-intensified chemotherapy compared with standard chemotherapy did not improve DFS, whereas the addition of darbepoetin might have detrimental effects on DFS.

Background: Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer. Strategies to improve efficacy include the use of anthracyclines, taxanes, and intensified dose with bone marrow support. Patients and methods: Patients received neoadjuvant epirubicin 90 mg/m 2 plus cyclophosphamide 600 mg/m 2 followed by paclitaxel 175 mg/m 2 (EC/T), each 3-weekly for four cycles (n = 370), or epirubicin 150 mg/m 2 followed by paclitaxel 225 mg/m 2 with pegfilgrastim followed by CMF (cyclophosphamide 500 mg/m 2 , methotrexate 40 mg/m 2 , fluorouracil 600 mg/m 2 ) on days 1 and 8 (Edd/Tdd/CMF), each 2-weekly and for three cycles (n = 363). Patients were randomly allocated to either simultaneous darbepoetin alfa (DA) (n = 356) or none (n = 377). Results: Pathological complete response (pCR) rate (breast) was higher with Edd/Tdd/CMF, 18.7% versus 13.2% with EC/T; P = 0.043, ypT0/Tis; ypN0 was reported in 20.9% versus 14.3% respectively; P = 0.019. Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate. Mean hemoglobin values maintained higher with DA (13.6 versus 12.6 g/dl). Edd/Tdd/CMF regimen showed more grade 3–4 mucositis, sensory neuropathy, and neurological complaints. Thromboembolic events were more frequent on DA (3% versus 6%; P = 0.055). Conclusion: Dose-dense and -intensified neoadjuvant chemotherapy with Edd/Tdd/CMF was potentially superior to EC/T in terms of pCR. Primary use of DA did not affect pCR.

Background: Despite progress in adjuvant breast cancer (BC) treatment, overtreatment due to decisions based on conventional prognostic factors (lymph nodes (LN), grade, tumor size) alone remains an important clinical problem. Recurrence Score®, RS is validated using pre-specified analyses, genes, cutt-offs in several randomized patient collectives as a potent prognostic and predictive marker in HR positive BC. Here, we present the first WSG-Plan B trial preplanned correlation analysis of central grade, nodal status, RS, and luminal A/B subtypes. Material and Methods: The West German Study Group (WSG) Plan B trial (planned n=2,448) is a randomized Phase-III-trial evaluating anthracyline-free adjuvant chemotherapy (Cht) (6x TC) vs. standard 4xEC-4xDOC in high-risk N0 and N+ HER2-negative BC. In HR+ BC with 0-3 LN, RS is the decision criterion for (>11) or against (≥11) Cht randomization. Tumor blocks are prospectively evaluated by a central pathologist for grade, histology and Ki-67. In HR+ disease, molecular subtypes (luminal A vs. B) are grouped using a Ki-67 cut-off of 13.25% (Cheang et al, JNCI 2009) and 20% (Penault-Llorca et al JCO 2009). Exploratory analysis with Elston-Ellis central grade and Ki-67 based (mitosis measured by Ki-67) grade will be performed. Results: As of June 2010, 1375 patients in 96 centers have been registered and 1067 randomized into Plan B. In 298 patients, RS results and clinical-pathological characteristics were available. In 266 patients complete information on all factors was available (132 N0, 134 N+). RS groups using the pre-specified trial cut-offs of 0-11, 12-25 and 30) were 48%, 38%, 14%. Central grade 1, 2, or 3 was observed in 4%, 50%, and 46% of cases. We observed a modest (Spearman) correlation between central grade and RS (e.g 83.8% of G3 tumors with RS >25, rs=0.331, P25), and guideline-recommended 30 (see table 1).Discussion: For the first time, we demonstrate a modest but significant correlation between centrally assed tumor grade, molecular classes by IHC Ki-67 cutt offs, and RS, particularly in the high RS group. However, our data also indicate that there is substantial discordance between the methods and thus an urgent need for optimzing risk-stratification classifiers. Table 1. Association of RS and molecular subtypes Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-12.

Background The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline–taxane–based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. Patients and methods Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms. Results With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1–3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. Conclusions Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline–taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. Clinical trial number NCT 00567554, www.clinicaltrials.gov .

The group of the so-called late preterms (infants born at 34 0/7-36 6/7 weeks gestational age) has been underestimated with respect to their neonatal outcome. Among infants born before the 29th week of pregnancy, a gender-specific difference in favour of females regarding morbidity became evident. The aim of this study is to investigate whether these findings are transferable to the group of late preterms.The neonatal outcome of 528 consecutive singletons, born at 34 0/7-36 6/7 weeks gestational age and requiring intensive care, was examined.Neonatal complications have been particularly analysed with regard to gender-specific differences. Boys (n=292) were significantly more frequently affected by sepsis (3.8 vs. 0.9%; p=0,0314, x²-test). Girls had significantly longer stays in the neonatal intensive care unit (median 12 (Q1:8; Q3:17) vs. 11 (6;16) days; p=0.0149, t-test). In a multiple logistic regression model, male gender and premature rupture of membranes were borderline significant with respect to the occurrence of sepsis - boys had a 4.4-fold risk (OR=0.228 [95% CI: 0.050-1.041]; p=0.0564) and premature rupture of membranes had a 3.5-fold risk (OR=3.462 [0.938-12.779]; p=0.0623). Strong cause variables for the length of stay in the neonatal intensive care unit were birth weight, gestational age and premature rupture of membranes after adjustment.The influence of foetal gender on the neonatal outcome in the late preterm group (34 0/7-36 6/7 gestational age) has been relativised.

Einleitung: Bis in die spaten 90er-Jahre haben die meisten Studien beim Mammakarzinom keine Patientinnen jenseits des 65. Lebensjahres eingeschlossen. Daher harren viele Fragen fur diese zunehmend groser werdende Altersgruppe der Beantwortung. Die ICE-Studie widmet sich der Frage nach der Durchfuhrbarkeit und der Wertigkeit der adjuvanten Chemotherapie in dieser Altersgruppe. Design/Methoden: Die Indikationsstellung erfolgt in Extrapolation der St. Gallen Leitlinien. Randomisierbar sind Frauen uber 64 mit einem N+ Mammakarzinom oder einer N0 Hochrisikosituation (Tumordurchmesser >2cm und/oder G II/III und/oder HR negativ). Zum Ausschluss von Patientinnen, deren Lebensspanne fuhrend durch die Komorbidat bestimmt wird, erfolgt die Beurteilung anhand des Charlson Score und des VES 13-Score. Therapie: Alle Patienten erhalten Ibandronat (p.o. oder 6mg i.v.) uber 2 Jahre und bei hormonrezeptorpositiven Tumor sequenziell Anastrozol uber 5 Jahre. Randomisiert werden 6 Zyklen Capecitabine 2000mg/m2p.o. b.i.d Tag 1–14 q3w versus nihil. Primares Studienziel: Vergleich des ereignisfreien Uberlebens. Sekundare Studienziele: Vergleiche des Gesamtuberlebens, der Compliance, Nebenwirkungen, Lebensqualitat, Anzahl osteoporosebedingter Ereignisse, geriatrische Beurteilung und die Bestimmung der Praferenz fur orale oder intravenose Gabe des Biphosphonats. Statistik: Angenommen wird eine Verbesserung des ereignisfreien Uberlebens von 65% auf 71,5% durch die adjuvante Chemotherapie. Bei einem a-Fehler von 5%, einem b-Fehler von 20% betragt die Zielzahl 1394. Ergebnisse: Von 4/04 bis 02/06 wurden insgesamt 517 Patientinnen randomisiert. (257 N-; 260 N+, 408 HR+). 62 SAEs wurden bislang gemeldet (54 Arm A/8 Arm B). Die Haupttoxizitaten beziehen sich auf Diarrhoe, Mukositis und Hand-Fus-Syndrome. Schlussfolgerung: Die bisher monitorierten Toxizitatsdaten und die gemeldeten SAEs sprechen fur die Durchfuhrbarkeit der adjuvanten Capecitabine-Therapie. Ein aktualisierter Statusreport wird vorgestellt.

Orchidectomy or testicular irradiation with 24 to 30 Gy are recommended for testicular involvement in boys with acute lymphoblastic leukemia. But, recommended radiation doses for the only occultly involved other testis differ, i.e. they range from 12 to 24 Gy. Low dose (12 or 15 Gy) "preventive" testicular irradiation was delivered to 5 of 14 patients; only one of these 5 experienced a further testicular relapse. According to our observation, in contrast to higher doses, the dose limitation allows spontaneous pubertal development including normal testosterone production and normal development of the masculine stature.

Mit dem Ziel einer flexiblen und objektangepassten flächenhaften Beleuchtung wurde ein frei programmierbarer LCD-Matrixmodulator entwickelt. Zur Messung von Materialeigenschaften unter thermischer Belastung wurden Systemkomponenten zur präzisen Temperaturregelung im Vakuum sowie zur Kleinsignalverstärkung implementiert.

Ausgehend von Bariumcarbonat-C wurde N-(2-Diathylaminoathy1)-S,S-diphenyl-sulfoximin in 8 Stufen in Position 1 der Seitenkette radioaktiv markiert (IA). Bezogen auf die Ausgangssubstanz betrug die radiochemische Ausbeute 44,6%. Zur Markierung in den Phenylgruppen (IB) wurde Benzol- (U-l4c) verwendet. Uber Diphenylsulfoxid und das entsprechende Sulfoximin wurde IB mit einer Ausbeute von 30,4% erhalten. Starting from barium carbonate-14C N-(2-diethylaminoethyl) - S,S-diphenyl-sulfoximine was labelled in position 1 of the side chain via 8 stages (IA). The overall radiochemical yield based on BaCO3 was 44.6%. For the labelling in the phenyl groups (IB) benzene-(U-14C) was used. Via diphenylsulfoxide and the corresponding sulfoximine IB was obtained with an overall yield of 30.4%.

This report deals with a cryopreservation technique and procedure; clinical data concerning the therapy itself are not presented here. A cryopreservation procedure was developed which proved to be effective for large volumes of lymphocytes and stem cells (CFU-c) obtained exclusively from the peripheral blood of man. Viability criteria used for lymphocytes include determination of the number of living cells, absolute recovery and immunologic assays. Stem cell counts and recovery were determined by the semisolid agar colony assay. A specially designed freezing process and a revitalization method using an atomizing system were applied to cell concentrates of patients with different types of cancer. The results indicate that nearly all cell functions of interest are fully preserved and that very high amounts of MNC and CFU-c are obtained after the freeze-thaw cycle. Up to now, units of cryopreserved autologous cells were retransfused to 40 patients.

DL-1-(3′-Hydroxyphenyl)-2-aminoathanol-hydrochlorid- (2-14C) wurde ausgehend von Kupfercyanid-14C in einer 2-Stufen-Synthese mit guter Ausbeute dargestellt. Dieser Syntheseweg ist auch zur 14C-Markierung anderer 1-Aryl-2-aminoathanole in Position 2 gut geeignet. DL-1-3-hydroxyphenyl)-2-aminoethanol-hydrochloride-(2-14C) was prepared with good yields by a two-step synthesis starting from copper cyanide-14C. The method described is also suitable for labelling of other 1-aryl-2-amino-ethanols in position 2 with 14C.

We report on 243 patients with sterilisation by the Bleier Clip. 234 patients were operated by coeliotomia posterior. 9 cases were sterilized in combination with Caesarean section. In 4 of 243 women we observed pregnancies during the follow-up period (failure rate = 16%). The mean time of the 4 conceptions after operation was 43 months. This result shows that the primary cause was not the operation technique but the systemic failure of the Bleier Clip. In cases with controls by hysterosalpingography all Fallopian tubes were occluded, 84% together with a sactosalpinx.

Pre-ejection period (PEP) and transcutaneous measured pO2 (tc pO2) were monitored simultaneously with the beat-to-beat ECG in 55 cases of unselected neonates. In addition body weight, acid-base-status and body temperature were registered 11 neonates were monitored immediately post partum, the others at various times until 9 days after delivery.The mean value of PEP after delivery is 63,3 msec. There is a negative correlation between neonatal heart rate and Pre-ejection-period. Increases of body temperature leads to a decrease of the PEP and vice versa. There are no direct significant alterations in PEP in connection with changes in neonatal tc pO2. Only when tc pO2-values beyond 20 mmHg were registered in distressed neonates PEP shortened significantly. PEP shortened also in periods of neonatal crying PEP is not correlated to birth weight or the actual neonatal weight when measurement of PEP and tc pO2 was performed.

Publisher Summary This chapter discusses the biochemical properties of the enigmatic chloroplast cytochrome b -559. The maximum heme content of the cytochrome that has been obtained is 58 nmoles heme/mg protein. In the early preparations, the heme content was much lower. The heme of cytochrome b -559 is more labile than that of cytochrome b 6 and it is difficult to stain the heme on a denaturing gel, even lithium dodecyl sulfate gel run at 0°C. As soon as the denaturing conditions of the gel are sufficient to allow the b -559 to penetrate, the heme is often lost. When the heterogeneity in the N-terminal residues in that preparation is considered, it appears likely that their heme content of one heme per 46,000 polypeptide molecular weight was a result of heme dilution because of heme loss and possibly contamination by other proteins. If high and low potential b -559 are derived from the same molecule, there should be no distinction in the purified cytochrome. However, one cannot eliminate the possibility that 20% of the cytochrome b -559 in the membrane is not extractable and that the unextractable component is phosphorylated.

Investigations on the metabolism of the new diuretic ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (Gö 687, etozolin, Elkapin) were carried out with urine of rat, dog and man as well as rat bile after enteral administration of the 14C-labelled substance. Seven metabolites were isolated with either the aid of high-pressure liquid chromatography (HPLC) or extraction and thin-layer chromatography. Mass spectroscopy was applied to determine the structures of the metabolites, partly by use of authentic reference substances. Because of the instability of most of the metabolites, some of them showing strong polarity, the described investigations on the metabolic profiles and the enrichment and purification of some metabolites could only be carried out with the HPLC-radioactivity detector system, which requires no clean-up for the samples. The metabolisation process of etozolin is qualitatively equal in rat, dog and man; it is characterized by 3 steps: 1. enzymatic cleavage of the ester group, which leads to the also diuretically active main metabolite (metabolite I) in the plasma of all 3 species; 2. glucuronidation of the resulting metabolite I, leading to metabolites II and III, which are diastereoisomeric esters of the two enantiomeric forms of metabolite I with beta-D-glucuronic acid. 50--60% of the urinary radioactivity can be described with these two metabolisation steps in all 3 species; 3. Oxidation of the piperidine moiety to metabolites IV--VII.

A new recording instrument for intrapartal parameters (fetal heart rate, uterine pressure, fetal transcutaneous oxygen pressure, local perfusion) records waveforms familiar to the obstetrician. The form of the recording corresponds to experience gained from cardiotocogram. The additional waveforms, oxygen pressure and perfusion are recorded synchronously in the recording channels of the other waveforms and are differentiated by special traces. This supplementary information given by the current oxygen-pressure waveforms can be comprehended synoptically. These parameter changes in respect to the fetal heart rate and uterine pressure can be identified clearly at a glance. Thus, the obstetrician is offered a recording of the monitored intrapartal parameters in waveforms which are familiar and extensively interpretable.

Fenoterol (Partusisten), which has a considerable influence on glucose metabolism in addition to its well-known cardiac side-effects, does not appear to have any direct influence on the P50 of the maternal erythrocytes in in-vitro experiments. In incubation experiments with fresh erythrocytes, fluctuations in the P50 with an amplitude of 2-5 mmHg were measured at +37 degrees C; these fluctuations depend on the storage age of the erythrocytes and the glucose content of the incubation medium. Fenoterol has no effect on the amplitude, nor on the frequency of this P50 fluctuation. The glycolytic activity of the erythrocytes, relative to the 2,3-DPG and ATP content, also remains uninfluenced under Fenoterol. The addition of progesterone or cortisone to the incubation medium has no influence on the P50 of the maternal erythrocytes. In-vivo studies of the blood of pregnant women indicate changes of the P50 with maximal "shift to the left" after 6 hours and compensatory "shift to the right" after 20 hours under tokolysis. No fluctuations of the pH value were observed in our patients. The intraerythrocytic 2,3-DPG concentration changes simultaneously with the P50. Venous pO2 increases by approx. 12 mmHg in the first 3 hours following the start of tokolysis. However, the changes in the venous pO2 are not simultaneous with the changes in the P50. It can be stated that the progesterone level has no influence on the release of O2 from the maternal blood.(ABSTRACT TRUNCATED AT 250 WORDS)

The surface layer of fetal epidermis in early pregnancy, the Periderm, is progressingly replaced by the final keratinization process during fifth to sixth month of gestation. Then the peridermal cells are shed into the amniotic fluid. It is still controversial, whether complete peridermal cells or just their globular protrusions are separated. Formation of mikrovilli and invaginations of plasma membrane, the numerous smaller and larger vacuoles and the cytoplasmatic meshwork of fine filaments without production of keratohyaline, are characteristics of peridermal cells, and are described in detail by electron microscopical investigations on cells suspended in the amniotic fluid, which are most likely of peridermal origin.

Nach der derzeit gultigen Lehrmeinung fuhrt die Progesteron-Wirkung in graviditate zu einer Hypotonie der Uretermuskulatur, die Dilatation des Schwangerschaftsureters wird auf hormonale Einflusse zuruckgefuhrt, mechanischen Komponenten wird nur untergeordnete Bedeutung beigemessen.

Jede Uteruskontraktion vermindert passager die Blutzufuhr in die Uterusgefase. Beim Rhesusaffen und auch beim Menschen konnte mit rontgenkinematographischen Untersuchungen nachgewiesen werden, das Wehen den Einstrom von Kontrastmittel in die Kotelydonen der Plazenta verlangsamen oder gar vollig stoppen (Ramsey et al. 1963; Boreil et al. 1964). Moll u. Kunzel (1974) konnten zeigen, das sich der Blutstrom in der A. uterina umgekehrt proportional zum Amniondruck verhalt.

The ultrastructural morphology of epidermal keratinocytes, which at the end of pregnancy and after shedding of vernix represent the majority of amniotic fluid cell population, is analysed by electron microscopy. Special attention is focused on the morphological characteristics of epidermal keratinization according the changes of the cell's ultrastructure during this process: The transformation of the cytoplasma into keratin, the formation of the typical cell membrane of the keratinized squamous cells, and the findings concerning the intercellular space, especially of the zones of intercellular contact - desmosomes - and their changes.

A literature review reports the results of investigations about fetal intrauterine activity. Different methods of observation are demonstrated and discussed. The results indicate that real-time-ultrasound is an accurate method for observation of fetal movements. Different patterns are identified: 1. Fetal body and extremity movements Development of fetal activity in early pregnancy is looked at as a process of maturation associated with fetal cerebral function. After 12 weeks of pregnancy typical patterns are established and seen also in the following weeks. Different results are reported about frequency of fetal movements related to duration of pregnancy. A circadian rhythm seems to be associated with a peak in activity between 2100 and 0100 hours, although fetal activity is altered by a variety of drugs and external stimuli. The proportion of pathological foetal movements in early pregnancy seems higher in patients who aborted. There are findings in later pregnancy, which report good fetal outcome, if daily fetal movement recording is greater than 10 movements for 12 hours. 2. Fetal breathing movements are recognized as being normally present, but episodic, shallow and variable in rate and regularity. There is a great variability in the percentage of time fetuses spend making breathing movements (mean 30-50% per hour; range 0-80%). Under physiological conditions there is a circadian rhythm concomitant with changes in fetal low-voltage electrocortical activity. The activation of fetal breathing occurs mainly during rapid-eye-movement-sleep, but the physiologic control of the activation has not been identified. Apnea, frequency, variability and amplitude of breathing, continuous breathing or gasping are described, but positive identification of abnormal pattern is not achieved. Several factors affecting fetal breathing movements have been described, their physiologic significance and control and their clinical relevance remain to be clearly elucidated. 3. Total fetal activity Fetal biophysical variables such as tone, breathing, body and extremity movements and heart rate reactivity are initiated and regulated by the fetal central nervous system, and as such, the presence of a given variable is indirect evidence of a functioning and intact central nervous system. These variable could be depressed by hypoxemia or other factors. Data in literature suggest that combined fetal biophysical testing is a more accurate method of antepartum fetal evaluation than any single method.

Quantitative and qualitative studies on lipids of the lungs were performed in babies who died during the perinatal period. The lungs were divided into organs with and without hyaline membranes respectively. Total lipids, phospholipids, neutral lipids, lecithins and sphingomyelins were determined. The fatty acid composition of total phospholipids and of lecithins is reported. A multivariate analysis of variance was used for the verification of significant differences in lipid content and in fatty acid composition with regard to the histological diagnosis. Taking at least two parameters (total phospholipids and C: 14-fatty acid or lecithin and C: 14-fatty acid into account, the two groups (lungs with and without hyaline membranes) were significantly different at the 5% level. The results are compared as well with the lipid content and composition of fatty acids of normal neonatal lung tissue as with observations regarding the lipids in amniotic fluid. The data obtained are discussed with regard to the development of lung maturity.

We performed preoperatively a psychiatric and psychosomatic exploration of women who came to us with a request for performing breast-corrective surgery. 18 months after the operation, these women were again examined both gynaecologically and psychosomatically. Subsequent to a postoperative course without complications and with primary wound healing, 88% of the surgically treated women considered the result to be in accordance with their expectations, and the size of their breast as adequate. Analysis of variance of the personality data reveals that patients with hypoplasia or hyperplasia of the breast do not differ from each other in respect of their personality characteristics. Preoperatively, the patients assessed themselves on the average very negatively with regard to social resonance, and proved to be very depressive. After plastic surgery of the breast, i.e. after anatomic correction, definite changes are seen in the mental field. A significant improvement is noticeable in the way the patients experience themselves, their body, and their self-value. The same also applies to the experience of their sexuality, to social relationships and social resonance, social potency, and partner relationship. All these were assessed by the patients as considerably improved (significant on the 1% level).

Because of premature labour, probability of fetal retardation, discrepance at term of delivery, Rh-incompatibility or EPH-gestosis 185 patients were hospitalized. 76 pregnant women received twice 1.5 ml Celestan Depot i.m. (4.5 betamethasone acetate and 6mg betamethasome dinatrium phosphate per injection) within an interval of 24 hours. It was necessary to maintain a tocolysis for at least 48 hours as a minimum after the first injection of Celestan Depot. The other 109 patients without treatment of glucocorticoids were considered as a controlgroup. We could show that antepartum application of betamethasone before the 38. week of gestation was associated with a reduction of RDS in our premature infants. Only one baby of the betamethasone-treated infants died of hyaline membrane disease during the first 7 days of life compared with 11 of the control group. In 11 patients patients amniocentesis was performed before the first injection of glucocorticoids and was repeated 2 to 7 days later. The amniotid fluid lecithin phosphorus concentration was determined. In the same period of pregnancy and the same iterval the lecithin phosphours level of amniotic fluid was analysed in 11 other patients who were not rreated with glucocorticoids. The difference between amniotic fluid lecithin phosphorus concentration in the first and second anslysis was found significant by a level of significance of alpha = 5%. There was no evidence of an influence of the therapy with Celestan Depot on this increase. The excretion of oestorgens in the urine of 24 hours was analysed in 22 gradidae before and 7 days after the treatment with betamethasone. The oestogen values of the day before application of betamethasone served as baseline figures. All patients showed a market fall in urinary oestrogens excretion, especially after the second day of therapy. After day 2 the values returned rapidly to baseline values. There were no differences between treated and control groups in Apgar scores at birth or in the incidence of icterus neonatroum (bilirubine level is greater that 10 mg% in the serum). The results of our study support the hypothesis that in humans glucocorticoid administration to the fetus accelerates lung maturation. Relatively brief intrauterine exposure of human infants to pharmacological doses of betamethasone was associated with a substantial reduction in the incidense of RDS.