TY - JOUR A1 - Beck, Eberhard A1 - Bittl, A. A1 - Koller, S. A1 - Merkle, E. A1 - Katalinic, A. A1 - Jäger, W. A1 - Lang, N. T1 - Erfassung der fetalen Retardierung mittels Ponderal Index und Gewichtsperzentilen Assessment of Fetal Retardation via Ponderal Index and Weight Percentiles JF - In: Geburtsh Frauenheilk 59(1999)2, 62-69 N2 - Zusammenfassung Intrauterin wachstumsretardierte Neugeborene konnten ihr genetisches Wachstumspotential aufgrund einer intrauterinen Mangelversorgung nicht realisieren und werden deshalb zu klein oder zu leicht geboren. Das Merkmal „zu leicht” wird mit Hilfe von Gewichtsperzentilen quantifiziert. Kinder mit einem Gewicht< 10. Perzentile werden als „small for gestational age” (SGA) bezeichnet. Diese Einteilung berücksichtigt jedoch nicht die Proportionen eines Neugeborenen, so daß vor allem asymmetrisch retardierte Neugeborene, deren Gewicht zwar die 10. Perzentile noch überschreitet, die jedoch für ihre Körpergröße untergewichtig sind, nicht erfaßt werden. Der Ponderal Index (PI) dagegen berücksichtigt sowohl Gewicht als auch Länge des Neugeborenen. Kinder mit einem PI < 10. Perzentile werden als „low Ponderal Index” (LPI) klassifiziert. Aus pädiatrischen Studien ist bekannt, daß LPI-Kinder vermehrt durch Hypoglykämien, Hypothermien, Hypokalzämien und Mekoniumaspirationen/Aspirationspneumonien gefährdet sind. Langzeiterhebungen zeigten eine verzögerte körperliche Entwicklung und gehäuft motorische oder neurologische Verhaltensauffälligkeiten sowie schulische Probleme. Fragestellung: Ziel der vorliegenden Arbeit war die Frage, ob Mangelgeborene, insbesondere LPI-Neugeborene, auch intrapartum einer erhöhten Gefährdung ausgesetzt sind. Methoden: Hierzu wurden 3687 Neugeborene retrospektiv erfaßt, die anhand von Perzentilenkurven des betrachteten Kollektivs als SGA, LPI, SGA/LPI oder Vergleichskollektiv klassifiziert wurden. Ergebnisse: Unterschiede im Geburtsmodus zwischen SGA- bzw. LPI-Mangelgeborenen und eutrophen Neugeborenen waren schwach ausgeprägt. Demgegenüber unterschied sich die Indikation, aufgrund deren ein geburtshilflicher Eingriff vorgenommen werden mußte deutlich. Bei 31 % aller operativ entbundenen LPI-Neugeborenen, 47 % der SGA-Neugeborenen und 52 % der SGA/LPI-Kinder erfolgte die operative Entbindung aus fetaler Indikation, im Vergleich zu 16 % des Normalkollektivs. Bezüglich des „fetal outcome”, das die Merkmale neonataler Säure-Basen-Status, Apgar-Wert, Verlegung in die Kinderklinik und perinatale Mortalität einbezog, verhielten sich die Gruppen SGA, LPI und SGA/LPI in gleicher Weise schlechter gegenüber dem Vergleichskollektiv. Die Unterschiede zwischen proportionierten (SGA) und dysproportionierten (LPI) Mangelgeborenen waren weniger deutlich. Schlußfolgerungen: Es zeigte sich, daß das gegenwärtige engmaschige, geburtshilfliche Management mit nahezu permanenter CTG-Überwachung sub partu Probleme rechtzeitig erkennen und beherrschen ließ. Die Erfassung des niedrigen Ponderal Index war zur Erkennung und Vermeidung subpartaler geburtshilflicher Risikofaktoren nicht entscheidend. N2 - Abstract Intrauterine growth retarded fetuses could not realize their genetic potential due to intrauterine malnutrition and could thus not reach an appropriate length or weight according to their gestational age. New born infants below the 10 th percentile are termed „small for gestational age” (SGA). However, this definition does not account for asymmetrically retarded infants who's birth weight is above the 10th percentile, but who are underweight for their length. In contrast the fetal Ponderal Index (PI) regards both fetal length and weight. New born infants with a PI <10th percentile are classified as „low Ponderal Index” (LPI). From pediatric studies it is well known that LPI infants are more likely threatened by hypoglycemia, hypothermia, hypocalcemia and meconium aspiration pneumonitis. Long term follow-up studies showed a retarded physical and mental development of these infants. Purpose: The current study followed the question if intrauterine growth retarded fetuses, esp. LPI infants are also at higher risk during labour. The data of 3687 new born infants were retrospectively analyzed. Study Design: According to their birth weight and length they were characterized as SGA, LPI, SGA/LPI or „appropriate for gestational age” AGA. The AGA infants together with the LGA infants were used as control group. Results: No significant differences in respect to birth modalities (i.e. vaginal delivery, cesarean section, operative vaginal delivery) could be detected between SGA-, LPI- and AGA infants. However, concerning the indication which formed the basis for an operative delivery, we found significant differences. In 31 % of all operatively delivered LPI new born, 47 % of the SGA infants and 52 % of the SGA/LPI group the indication for the operative management was based on fetal problems. This indication accounted for only 16 % of the operatively delivered infants in the control group. Regarding the fetal outcome, specified by the fetal acid base status, Apgar index, frequency of transfer to the neonatal intensive care unit, and perinatal mortality, no differences between LPI, SGA and SGA/LPI infants could be detected. Conclusion: We conclude that the current strategies of monitoring labour, e.g. by continuous CTG scanning, are sufficient to detect and master fetal problems. The detection of a „low Ponderal index” did not add any information concerning the management of labour. Y1 - 1999 SP - 62 EP - 69 ER - TY - JOUR A1 - Beck, Eberhard A1 - Moldenhauer, A. A1 - Merkle, E. A1 - Kiesewetter, F. A1 - Jäger, W. A1 - Wildt, L. A1 - Lang, N. T1 - CA 125 production an release by ovarian cancer cell lines in vitro JF - In: The international journal of biological markers 13(1998), 200 – 206 Y1 - 1998 SP - 200 EP - 206 ER - TY - CHAP A1 - Beck, Eberhard A1 - Moldenhauer, A. A1 - Kiesewetter, F. A1 - Jäger, W. A1 - Woldt, L. A1 - Lang, N. T1 - Analysis of CA 125 production and release by ovarian cancer cells in vitro T2 - In: Current tumor diagnosis : applications, clinical relevance, research - trends / 7th Symposium on Tumor Markers, Hamburg 1993 ; Satellite Symposium Cancer of the Lung - State and Trends in Diagnosis and Therapy. Ed. by R. Klapdor. - München [u.a.] : Zuckschwerdt, 1994. - ISBN 3-88603-509-3 Y1 - 1994 SP - 187 EP - 191 ER - TY - JOUR A1 - Beck, Eberhard A1 - Hofmann, M. A1 - Bernhardt, G. A1 - Jäger, W. A1 - Wildt, L. A1 - Lang, N. T1 - In vitro activity of immunoconjugates between cisplatin and an anti CA125 monoclonal antibody on ovarian cancer cell lines JF - In: Cell Biophysics 24/25(1994)1-3, 163-173 N2 - Cis-diammine dichloro platinum (II) (CDDP), is a highly potent antineoplastic agent that is used in the treatment of ovarian cancer. However, the clinical use of CDDP is restricted by its severe side effects. In order to reduce these side effects and to enhance its therapeutic efficacy, we developed specific immunoconjugates consisting of the murine monoclonal antibody OC125 and CDDP, using diethylene triamine pentaacetic acid (DTPA) as a linker. The coupling efficiencies of the different preparations synthesized, varied between 1.10±0.42 and 2.65±1.60 mol of CDDP per mol of antibody protein. Despite the chemical modification of the antibody molecule, specific binding activity of the OC125-CDDP conjugates toward the CA125 antigen was maintained as was demonstrated by means of immunohisto-/cytochemical staining of frozen sections of ovarian cancer tissue, amniotic epithelium, and the CA125 positive ovarian cancer cell line NIH:OVCAR 3. The antiproliferative activity of the immunoconjugates was tested against the human ovarian cancer cell lines NIH:OVCAR3 and SKOV 3, applying a kinetic crystal violet microassay. Despite the promising results obtained with the specific immuno-staining of the target cells, no significant antiproliferative activity of our immunoconjugates against the cell lines tested was observed. One possible explanation for the lack of antitumor activity could be the fact that CA125 is released in large amounts by the NIH:OVCAR 3 cells. This may have prevented an efficient immunotargeting of the cancer cells by the formation of soluble immune complexes. Y1 - 1994 SN - 0163-4992 SP - 163 EP - 173 ER - TY - JOUR A1 - Beck, Eberhard A1 - Russo, P. A1 - Papa, V. A1 - Jäger, W. A1 - Pezzino, V. A1 - Wildt, L. A1 - Vigneri, R. A1 - Lang, N. T1 - Nachweis von Insulin-Rezeptoren (IR) in Ovarialkarzinomgewebe JF - In: Archives of Gynecology and Obstetrics December 254(1993)Iss. 1-4, 1053-1054 Y1 - 1993 SN - 0932-0067 SP - 1053 EP - 1054 ER - TY - JOUR A1 - Merkle, E. A1 - Ackermann, S. A1 - Beck, Eberhard A1 - Jäger, W. A1 - Lang, N. T1 - High-Dose versus Low-Dose Cisplatin Chemotherapy plus Treosulfan in Epithelial Ovarian Carcinoma FIGO II–IV: Results of a Prospective Randomized Trial JF - In: Onkologie 23(2000)3, 232-238 N2 - Summary Background: Combination chemotherapies of platinum compounds with alkylating agents have been the standard treatment for patients with advanced ovarian carcinoma over the last decades. The recent development of taxans has added a group of new promising agents; however, long-term results are not yet available. Platin derivates have proven to be an indispensable part in combination chemotherapies for ovarian carcinoma. The dose intensity of cisplatin is, however, still a matter of debate. We report on the long-term results of a prospective randomized trial comparing two dosages of cisplatin combined with treosulfan in patients with advanced epithelial ovarian cancer. Patients and Methods: Between 1988 and 1995, 125 patients with ovarian cancer (FIGO stage II–IV) were randomized to receive 4 cycles (28-day intervals) of either cisplatin 100 mg/m2 (high dose, HD) or 50 mg/m2 (low dose, LD) in combination with 5 g/m2 treosulfan after primary cytoreductive surgery. Postoperative residual tumor was absent in 39 patients (HD: 16; LD: 23), < 2 cm in 61 patients (HD: 36; LD: 25) and > 2 cm in 25 patients (HD: 13; LD: 12). 65 and 60 patients received HD and LD cisplatin, respectively. Second-look surgery was optional. Results:The overall response rate was 70.0% (HD: 70.9%; LD: 68.9%). Pathological complete response (CR) was seen in 45 patients (37.5%), clinical CR in 23 patients (19.2%), partial response (PR) in 16 patients (13.3%), stable disease (SD) in 2 patients, and progression of disease (PD) in 34 patients (28.3%). 5 patients were not assessable for response. Overall median survival was 25.6 (HD: 26.9, LD: 25.2) months. The overall disease-free survival for responders was 19.6 and 24.7 months (HD and LD, respectively). HD chemotherapy did not result in any significant survival benefit in completely resected patients: HD: 39.8 months versus LD: 49.5 months. In suboptimally debulked patients (residual tumor < 2 cm), median survival was 24.1 months (HD) versus 22.6 months (LD). In patients with residual tumors > 2 cm median survival was 14.6 months (HD) versus 15.5 months (LD). Significantly less side effects were seen in the LD group: anemia (p = 0.008); nephrotoxicity (p = 0.014); alopecia (p = 0.017). Conclusions: Our data suggest that LD cisplatin-based chemotherapy is as effective as HD chemotherapy in patients with advanced epithelial ovarian cancer, but is far less toxic. Copyright © 2000 S. Karger GmbH, Freiburg Y1 - 2000 SP - 232 EP - 238 ER - TY - JOUR A1 - Beck, Eberhard A1 - Vincenti, D. A1 - Licht, P. A1 - Berkholz, A. A1 - Jäger, W. A1 - Lang, N. A1 - Merkle, E. T1 - In vitro activity of human chorionic gonadotropin (hCG)--doxorubicin conjugates against ovarian cancer cells JF - In: Anticancer research 20(2000)5A, pg 3001-6 N2 - BACKGROUND Despite radical surgery and the introduction of novel chemotherapeutic agents, the prognosis of ovarian cancer remains poor. Since in the past the potential role of gonadotropins in the induction and progression of ovarian cancer has been discussed, we conjugated doxorubicin to human chorionic gonadotropin (hCG) in order to specifically target ovarian cancer cells. MATERIALS AND METHODS Doxorubicin was conjugated to hCG via glutaraldehyde. 48 hours post seeding, NIH:OVCAR 3 cells were treated with various concentrations of hCG-conjugated and non-conjugated doxorubicin for 2 hours. Cells were cultured for a total of 168 hours. Cell growth was monitored by a crystal violet assay. RESULTS Conjugating doxorubicin to hCG resulted in an average specific uptake of 22 mol doxorubicin per mol protein (range 3.0-43.3 mol). Incubating NIH:OVCAR 3 cells for 2 hours with the conjugate led to a more than 8 fold increase of the IC50 values compared to non-conjugated doxorubicin (0.55 microM versus 4.43 microM). The antiproliferative activity of both conjugated and free doxorubicin was detectable up to 168 hours post treatment. CONCLUSIONS The present experiments clearly demonstrate a more than 8-fold increase in cytotoxicity of the conjugates compared to free doxorubicin. It was also shown that this effect was not restricted to an acute toxic event but that it resulted in a prolonged antiproliferative activity. KW - Antineoplastic Agents KW - Cell Division KW - Cell Survival KW - Chorionic Gonadotropin KW - Drug Synergism Y1 - 2000 SP - 3001 EP - 3006 ER - TY - CHAP A1 - Beck, Eberhard A1 - Hofmann, M. A1 - Kiesewetter, F. A1 - Jäger, W. A1 - Wildt, L. A1 - Lang, N. T1 - Analysis of CA 125 release by ovarian cancer cells in vitro T2 - In: Tumor associated antigens, oncogenes, receptors, cytokines in tumor diagnosis and therapy at the beginning of the nineties / 6th Symposium on Tumor Markers, Hamburg, [December 9. - 11. 1991] ; Satellite Symposium Cancer of the Breast - State and Trends in Diagnosis and Therapy. Ed. by R. - München [u.a.] : Zuckschwerdt, 1992. - ISBN 3-88603-444-5 Y1 - 1992 SP - 117 EP - 121 ER - TY - CHAP A1 - Beck, Eberhard A1 - Seidinger, M. A1 - Schneider, G. A. A1 - Schuster, M. A1 - Berg, A. A1 - Jäger, W. A1 - Wildt, L. A1 - Lang, N. T1 - Toxische Schädigungen des Gehörs unter Cisplatinhaltiger Chemotherapie bei Patientinnen mit gynäkologischen Tumoren T2 - In: Zytostatikabedingte Nebenwirkungen : Symposium in Pommersfelden, 3. - 4. Juli 1992 ; 26 Tabellen / Bd-Hrsg.: N. Lang ... - München [u.a.] : Zuckschwerdt, 1993. - Aktuelle Onkologie ; 8). - ISBN: 3-88603-458-5 Y1 - 1992 SP - 5 EP - 9 ER - TY - CHAP A1 - Jäger, W. A1 - Löffler, B. A1 - Beck, Eberhard A1 - Bellmann, O. A1 - Wolf, A. A1 - Mund-Hoym, S. A1 - Sauerbrei, W. A1 - Wildt, L. A1 - Lang, N. T1 - Retrospective analysis of GnRH analogue administration in patients with advanced ovarian cancer T2 - In: GnRH analogues and cancer : plus a review of the treatment of uterine leiomyomata; the proceedings of the 2. International Symposium on GnRH Analogues in Cancer and Human Reproduction, Geneva, November 1990 / ed. by B. Lunenfeld. - Carnforth, Lancs. [u.a.] : Parthenon Publ., 1992. - (Advances in the study of GnRH analogues ; 4). - ISBN: 1-85070-328-0 Y1 - 1992 SP - 69 EP - 76 ER -