Search

Background The effective detection and monitoring of potentially malignant oral lesions (PMOL) are critical to identifying early‐stage cancer and improving outcomes. In the current study, the authors described cytopathology tools, including machine learning algorithms, clinical algorithms, and test reports developed to assist pathologists and clinicians with PMOL evaluation. Methods Data were acquired from a multisite clinical validation study of 999 subjects with PMOLs and oral squamous cell carcinoma (OSCC) using a cytology‐on‐a‐chip approach. A machine learning model was trained to recognize and quantify the distributions of 4 cell phenotypes. A least absolute shrinkage and selection operator (lasso) logistic regression model was trained to distinguish PMOLs and cancer across a spectrum of histopathologic diagnoses ranging from benign, to increasing grades of oral epithelial dysplasia (OED), to OSCC using demographics, lesion characteristics, and cell phenotypes. Cytopathology software was developed to assist pathologists in reviewing brush cytology test results, including high‐content cell analyses, data visualization tools, and results reporting. Results Cell phenotypes were determined accurately through an automated cytological assay and machine learning approach (99.3% accuracy). Significant differences in cell phenotype distributions across diagnostic categories were found in 3 phenotypes (type 1 [“mature squamous”], type 2 [“small round”], and type 3 [“leukocytes”]). The clinical algorithms resulted in acceptable performance characteristics (area under the curve of 0.81 for benign vs mild dysplasia and 0.95 for benign vs malignancy). Conclusions These new cytopathology tools represent a practical solution for rapid PMOL assessment, with the potential to facilitate screening and longitudinal monitoring in primary, secondary, and tertiary clinical care settings., A point‐of‐care oral cytology tool has been developed for the noninvasive detection and monitoring of potentially malignant oral lesions. The distribution of cell phenotypes identified by machine learning and a cytology‐on‐a‐chip approach provides useful information as part of the assessment of oral lesions, with improved interpretability, calibration, and generalizability compared with conventional methods.

Die Internationalen Gesundheitsvorschriften (IGV) von 2005 wurden durch das „Gesetz zu den Internationalen Gesundheitsvorschriften“ vom 20. Juli 2007 in deutsches Recht uberfuhrt und mittels eines Durchfuhrungsgesetzes (IGV-DG) inhaltlich genauer ausgestaltet. Somit mussen „benannte Flughafen“ („designated airports“) Kernkapazitaten zum Schutz vor gesundheitsriskanten Bedrohungslagen vorhalten und sogenannte IGV-Ubungen durchfuhren. Darstellung der Optimierung etablierter Einsatzkonzepte unterschiedlichster Professionen zum Management infektionsbiologischer Bedrohungslagen ohne Behinderung des internationalen Reiseverkehrs und Vermittlung von Erfahrungswerten an Akteure in IGV-Verantwortlichkeit. Basierend auf einem kombiniertem Ubungskonzept wurde am 11. November 2013 erstmals in der Bundesrepublik Deutschland eine IGV-Ubung anhand des Fallszenarios einer reiseassoziierten fiebrigen Erkrankung an einem „benannten Flughafen“ unter Einbindung aller relevanten Akteure durchgefuhrt. Der Zeitraum fur die Organisation der gesamten Ubung umfasste sechs Monate, die Ubung an sich 12 h und die Nachbereitungszeit neun Monate. Nachfolgend wurde sowohl eine qualitative als auch eine quantitative Evaluation des Ubungsgeschehens bewerkstelligt. Grundsatzlich erwiesen sich modulare Arbeitsstrukturen und die Risikokommunikation aus individual- und bevolkerungsmedizinischer Sicht als funktionsadaquat. Optimierungsbedurftig waren die An- und Abfahrtszeiten involvierter flughafenexterner Akteure, der Transport der Indexpatientin zum versorgenden Krankenhausund der Individualschutz einzelner Einsatzkrafte. Hingegen konnte die Umgebungsuntersuchung bei den Mitreisenden zielfuhrend ausgestaltet werden. In der Gesamtsicht konnte ein definiertes biologisches Bedrohungsszenario basierend auf einer Doppelinfektion mit zwei hochpathogenen Krankheitserregern ohne Beeintrachtigung des internationalen Luftverkehrs zufriedenstellend bearbeitet werden. Modulare Versorgungskomponenten sind bei Bedrohungsszenarien im internationalen Flugreiseverkehr zielfuhrend und zukunftsweisend. Innerhalb des Einsatzgeschehens sind eine zeitnahe Mobilitat, ein funktionstuchtiger Selbstschutz unmittelbar involvierter Akteure nebst der Risikokommunikation und vor allem eine koordinierende Begleitung der Gesamtsituation von herausragender Bedeutung.

Die Spinalanasthesie wird als das Standardanasthesieverfahren zur Sectio caesarea angesehen. Zahlreiche Studien befassen sich mit der Dosisfindung der applizierten Lokalanasthestikamenge und -konzentration, um das Auftreten einer haufig assoziierten Hypotonie zu reduzieren. Die am Universitatsklinikum Wurzburg etablierte Technik der „High-volume-low-concentration“-Medikamentenkombination aus bis zu 12 ml isobarem 0,1 %igem Bupivacain (1 mg/ml) mit Sufentanil (1 µg/ml) ist bislang wenig verbreitet und wurde in dieser retrospektiven Studie hinsichtlich Zuverlassigkeit und Nebenwirkungen untersucht. Von 1424 Anasthesieprotokollen aus den Jahren 2001–2007 wurden 1368 ausgewertet. Erfasst wurden demografische Daten sowie Parameter wie Punktionshohe, Dosis und Ausdehnung, Kreislaufstabilitat und Medikamentenbedarf wahrend der Spinalanasthesie. Als Hypotoniegrenze wurde ein Abfall des systolischen Blutdruckwerts auf

Maternale Hepatopathien stellen eine Bedrohung in Schwangerschaft sowie Wochenbett und eine Herausforderung fur behandelnde Arzte dar. Die Leberaffektionen konnen ein breites Spektrum an schwangerschaftsassoziierten und –unabhangigen Erkrankungen wie HELLP-Syndrom, Leberentzundungen oder akute Schwangerschaftsfettleber zur Ursache haben. In dieser Studie stellen wir eine Serie von 3 lebensbedrohlichen Verlaufen peripartaler Hepatopathien vor und diskutieren diesbezuglich den aktuellen Wissensstand mit einem speziellen Augenmerk auf pathogenetische Zusammenhange und mogliche Differenzialdiagnosen. Pathologische und radiologische Begutachtungen wie auch gynakologische oder chirurgische Masnahmen wurden entsprechend den geltenden Leitlinien durchgefuhrt. Laborchemische Untersuchungen wurden in den Routinediagnostik-Abteilungen der Universitatskliniken durchgefuhrt. Literatur wurde uber das durch die US National Library of Medicine bereitgestellte Verzeichnis „PubMed.gov“ selektiv recherchiert. Im ersten Fall kam es nach Entbindung bei fulminantem HELLP-Syndrom in der 32. Schwangerschaftswoche (SSW) zu einem subtotalen Leberinfarkt mit folgender schwerer Gerinnungsstorung und septischer Peritonitis. Die zweite Patientin wurde bei mildem HELLP-Syndrom in der 36. SSW entbunden. Postpartal verschlechterte sich die Erkrankung rasant und mundete in einen hamorrhagischen Schock mit akutem Nierenversagen. Die dritte Geburt fand mit 36 SSW bei asymptomatischer Hepatitis B statt. Die Hepatitis exazerbierte nach Entbindung mit der Entwicklung einer subakuten Leberdystrophie mit ausgepragter Gerinnungsstorung. Wenn mutterliche Leberaffektionen im Zusammenhang mit Schwangerschaften auftreten gilt es, verschiedene Diagnosen und unterschiedlicher Pathogenese zu berucksichtigen. Diagnostische und therapeutische Ansatze mussen rasch abgewogen werden. Ferner ist eine schnelle, effektive interdisziplinare Zusammenarbeit notwendig, um Folgeschaden zu minimieren und das Uberleben der betroffenen Patientinnen zu sichern, weil fulminante bis todliche Verlaufe auch heute immer noch moglich sind.

Der vorliegende Beitrag behandelt die medikamentose Tumortherapie, basierend auf dem Einsatz von Antagonisten des Gonadotropin-Releasing-Hormon (GnRH) und des Growth-Hormon-Releasing-Hormon (GHRH) sowie Analoga des GnRH als Tragersubstanz fur Chemotherapeutika. Mammakarzinome exprimieren Rezeptoren fur GnRH in 50% und fur GHRH in 35% der Falle. Die Expression und der wachstumsstimulierende Effekt der jeweiligen Liganden GnRH und GHRH sind in dieser Tumorentitat ebenfalls nachgewiesen, sodass sich hier eine „targeted therapy“ mit antagonistischen Analoga dieser Peptidhormone anbietet. Andererseits konnen GnRH-Rezeptoren auf Mammakarzinomzellen auch als Zielstrukturen fur eine rezeptorvermittelte Chemotherapie mit zytotoxischen Hybriden, bestehend aus einem GnRH-Analogon und einem zytotoxischen Radikal, dienen. Durch diese Therapieform soll eine hohere Wirkstoffkonzentration des Chemotherapeutikums im Tumor erreicht werden. So soll die antitumorale Wirkung gesteigert und gleichzeitig sollen die Nebenwirkungen minimiert werden. Im Folgenden werden die zu diesem Thema durchgefuhrten praklinischen und klinischen Studien zusammengefasst.

Resume Objectif Evaluer la faisabilite, la securite et l’efficacite sur les symptomes d’une injection intra-articulaire (IA) d’hylan G-F 20, chez des patients souffrant d’une omarthrose sans rupture de la coiffe des rotateurs. Methodes Etude prospective, multicentrique, ouverte chez des patients souffrant d’une omarthrose sans rupture de coiffe symptomatique (EVA douleur ≥ 40 et ≤ 90 mm). Les patients ont recu une injection IA, sous controle scopique, de 2 ml d’Hylan G-F 20, avec possibilite d’une seconde injection a un, deux ou trois mois si le soulagement des douleurs n’etait pas suffisant. Le critere principal d’evaluation etait la variation de l’intensite douloureuse sur l’EVA trois mois apres la derniere injection, les patients etant suivis six mois. Resultats Trente-neuf patients ont ete inclus, 33 ont recu une premiere injection et 16 une seconde ; 29 patients ont termine l’etude. Il n’y a pas eu d’effet indesirable serieux ou grave en rapport avec le traitement ; huit patients ont presente dix effets indesirables, tous d’intensite legere ou moderee. Le score moyen de douleur de l’epaule traitee a diminue de 61,2 a 37,1 mm a trois mois (p Conclusion Cette etude prospective montre que le traitement de l’omarthrose sans rupture de la coiffe des rotateurs avec une ou deux injections IA d’hylan G-F 20 est realisable, bien toleree et probablement efficace. Elle suggere que la viscosupplementation par hylan G-F 20 pourrait etre une option interessante pour les patients souffrant d’une omarthrose sans rupture de coiffe.

Bei der Therapie des Endometriumkarzinoms steht heute der operative Weg im Vordergrund und ermoglicht den stadiengerechten Einsatz zusatzlicher adjuvanter Masnahmen. Die Aufgabe der Diagnostik besteht darin, das operative Vorgehen moglichst individuell festzulegen. Der transvaginale Ultraschall ist eine kostengunstige, zumeist schmerz- und komplikationslose Methode in der Diagnostik des Endometriumkarzinoms. Sonographisch beurteilt werden Endometriumdicke, Echostruktur und Endometriumbegrenzung sowie – falls vorhanden – eine intrakavitare Flussigkeitsansammlung. Neben der konventionellen transvaginalen Sonographie (TVS) besteht die Moglichkeit einer Dignitatsbeurteilung mittels Farb- und Pulsdopplersonographie, z. B unter Verwendung von Pulsatility-Index und Resistance-Index. Bei der praoperativen Stadieneinteilung stellt die MRT bezuglich der Myometriuminfiltration und des zervikalen Befalls im Vergleich zu TVS und CT die praziseste Methode dar.

BACKGROUND AND OBJECTIVE Different from the situation in the USA, Canada, Israel, Italy and Great Britain transmission of electrocardiograms (ECG) by telephone plays an unimportant part in Germany because existing technology is at best adequate for the diagnosis of arrhythmias. A new simple system, the size of a mobile phone (P12, Aerotel, Israel), was tested: for the first time in Europe it allows patients themselves to obtain a 12-lead ECG and transmit it via any telephone to a centre for analysis. This system was evaluated for its reliability when used by lay persons. PATIENTS AND METHODS Qualitative and quantitative parameters of a conventional 12-lead ECG obtained in 217 patients (86 women, 131 men) were compared with those of 12-lead ECGs recorded and stored by lay persons, transmitted via telephone to a computer and then printed out. RESULTS All ECGs transmitted with the P12 were analysable: quality was good or very good in 86%. Heart rate, transmission time and the various durations agreed with the conventional leads, while P12 underregistered amplitudes by about 15%. This difference was correctable by a constant or by adjusting the ECG machine. Atrial fibrillation (in eight of eight cases), infarct changes (40 of 40), ST elevations or depressions (15 of 15) and T negativities (80 of 82) were also reliably recognized. CONCLUSIONS The described method proved simple and reliable. Clinically significant information in the ECG can be transmitted within minutes and with high diagnostic reliability to a central station via any telephone. P12 is thus suitable for self-recording of ECGs by patients with potentially dangerous cardiac conditions. However a centre with cardiologically trained personnel should be available where telephone transmission of the ECGs and dialogue with the patients is possible around the clock.

The finding of absent or reverse end-diastolic flow velocities (AREDV) in the umbilical artery already prior to viability corresponds to the most severe end of the clinical spectrum of placental insufficiency. However, there is little or no experience or published literature with regard to perinatal outcome. We report 2 cases in which structurally and chromosomally normal foetuses showed severe early onset retardation but were continuing to grow. These gestations could be prolonged by 62 and 64 days, respectively. Perinatal outcome was good in both following Caesarean section at 32+3 and 31+5 gestational weeks respectively.

Intestinal infection due to the pinworm Enterobius vermicularis is the most prevalent helminthiasis in Europe and North America. Humans are the only known reservoir and young children are most often affected. The disease is highly contagious and is transmitted via the faecal-oral route. Insufficient hand hygiene, contaminated bed linens and clothes may play a role in transmission. Clinical symptoms often encompass severe nocturnal anal pruritus, when female worms deposit an abundance of eggs in the perianal region. The infection is diagnosed by applying an adhesive tape on the perianal region, followed by microscopic examination. Serious complications, such as extraintestinal infections, occur only rarely. Infections of the female genital tract and the peritoneum are described in the literature, also in pregnant women. We describe a case of a pregnant patient in the 33 (rd) week of gestation with intense anal pruritus in whom an enteral pinworm infection was diagnosed. The patient was successfully treated with mebendazole, an anthelminthic agent. Analysis of the data currently available for the administration of mebendazole during pregnancy did not show an elevated rate of congenital anomalies. However, further studies still have to be performed.

Umbilical cord blood is being increasingly used as an alternative stem cell source in the treatment of children and adults with malignant and non-malignant diseases. Data regarding the outcome of children show promise. Furthermore, transplantation of cord blood from an unrelated donor should be considered as an acceptable alternative for adults in the absence of an HLA-matched bone marrow donor. In the past 10 years cord blood banking has become a world-wide reality. However, problems in cord blood banking are caused by the controversial and conflicting interests of public and private cord blood banks. The financial gains of certain private banks hinders the growth of stored units for public use and makes it difficult to find full matches for some patients, especially those groups with a high diversity of HLA types. Future trends should implement an increased capacity for multilineage differentiation of cord blood stem cells. Pluripotentiality might lead to therapeutic applications in regenerative medicine.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Wir berichten uber einen 78-jahrigen Patienten mit Zweikammerschrittmacher, der zur Kardioversion einer atrialen Tachykardie in unsere Klinik aufgenommen wurde. Nach transthorakaler Energieabgabe von 160 Joule manifestierte sich ein kompletter Exitblock mit totaler Ineffektivitat der ventrikularen Stimulation gefolgt von einem bradykarden Ersatzrhythmus. Die umgehende Analyse der Stimulationsreizschwellen ergab einen erheblichen Anstieg der Ventrikelreizschwelle bei unveranderter Vorhofreizschwelle. Die Stromeinwirkung bei externer Elektrokardioversion mit praferentiellem Stromfluss uber die Ventrikelelektrode kann uber eine myokardiale Schadigung des Ubergangs zwischen Elektrode und Endokard zu einer selektiven Dysfunktion der ventrikularen Stimulation fuhren. Zur Gewahrleistung einer effektiven Schrittmacherstimulation sollte insbesondere bei schrittmacherabhangigen Patienten vor geplanter Elektrokardioversion die maximale Stimulationsamplitude programmiert und die Schrittmacherfunktion nach erfolgter Stromabgabe sorgfaltig kontrolliert werden.

The endometrial carcinoma is meanwhile the most common malignant tumor of the female genital tract. 2 subtypes can be divided according the pathogenesis: the classical estrogen related endometroid type and the nonclassical estrogen unrelated serous type. The endometrial adenomatous hyperplasia as a precancerous lesion must be identified by subjective criteria. Therefore the histological diagnosis is worse reproducible. An improvement would be helpful by morphometric and molecular genetic methods. The golden standard of diagnosis of the endometrial carcinoma is fractional dilatation and curettage. Immunohistochemical staining with a limited panel of antibodies can discriminate between an endometrial and an endocervical origin of an adenocarcinoma. The corner stone of the therapy is surgery. An individual decision about postoperative treatment is very important and depends on histological criteria. The adjuvant postoperative whole pelvic radiation is under discussion whereas the vaginal brachytherapy is established as standard therapy. This article outlines an overview of the actual situation for pathogenesis, diagnosis and treatment endometrial cancer.

Significant placental insufficiency with Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV) is associated with increased morbidity and mortality. An analysis of blood flow in the ductus venosus assists in the early recognition of threatened foetuses. However, the prognostic value of multivessel Doppler assessment for the timing of delivery is being questioned. Four high-risk pregnancies with umbilical AREDV were repeatedly examined prior to intrauterine foetal demise. Our results demonstrate that ductus venosus Doppler flow velocimetry can be normal prior to intrauterine foetal death.

Nowadays Caesarean sections are mainly undertaken using spinal anesthesia; therefore, it is important to minimize potential side effects and risks associated with this technique. Currently, many studies have been conducted to optimize the dose of local anesthetics to avoid hypotension, which often occurs during spinal anesthesia.In a retrospective study design the high-volume, low-concentration technique with up to 12 ml isobaric bupivacain 0.1% (1 mg/ml) and sufentanil (1 µg/ml), which has been used at the University Hospital Würzburg for many years was analyzed with respect to reliability and side effects. The use of this technique so far is unique among university hospitals in Germany.Of the 1424 anesthesia protocols from 2001 to 2007 a total of 1368 were analyzed. Demographic data and parameters, such as location of puncture, dose and extent of anesthesia, hemodynamic stability and additional medication were recorded. A decrease of systolic blood pressure of more than 20% of the initial value was defined as hypotension.The median volume used for spinal anesthesia was 9 ml, containing 9 mg bupivacaine and 9 µg sufentanil. The rate of hypotension was 48.8 %. No significant differences in hypotension between lower and higher volumes were detectable. In 0.84% (n=12) of the cases the procedure had to be changed to general anesthesia and additional analgesia was administered in 3 cases (0.22%).The high-volume, low-concentration technique is an effective approach for spinal anesthesia with a small number of cases needing general anesthesia or additional analgesics. The rate of hypotension was moderate compared to other studies; however, because of the retrospective and non-randomized study design the dependence of this rate on dose and given volume should be interpreted with caution.

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.

Die Implantation ist ein ausergewohnlicher Vorgang in der Natur. Dabei sind der Embryo mit den Trophoblastzellen und das maternale Endometrium beteiligt. Der Trophoblast bildet Gefasverbindungen zur Versorgung des Fetus aus. Der molekulare Dialog zwischen dem implantierenden Konzeptus und der uterinen Dezidua betrifft Zell-Zell- und Zell-Extrazellularmatrix-Interaktionen, die durch Lektine, Integrine, matrixabbauende Enzyme und ihre Inhibitoren sowie durch eine Reihe von Zytokinen bewerkstelligt werden. Die Dezidua wird durch eine Population von CD56+CD16− naturlicher Killer(NK-)zellen mit einem distinkten Phanotyp infiltriert. Diese Zellen sind besonders bei der Implantation in groser Zahl vorhanden und treten in engen Kontakt mit dem invasiven Trophoblasten. Die selektive Expression des ungewohnlichen Klasse-I-human-leukocyte-antigen-(HLA-)Molekuls HLA-G durch den extravillosen Trophoblasten schutzt wahrscheinlich den invasiven Trophoblasten vor dem potentiellen Angriff maternaler NK-Zellen. Diese Ubersicht soll in Umrissen unseren derzeitigen Wissensstand uber die Implantation des Embryos auf zellularer und molekularer Ebene beschreiben.

Various mechanisms are necessary for regulating the survival of the semiallogenic embryo in the maternal organism. In addition to the lack of classical MHC class I and II antigens at the trophoblast the cytokines play an important role at the fetomaternal interface. Different cytokines regulate the immunological processes with an emphasis on the Th1/Th2 balance. In contrast to the peripheral blood there is a certain composition of immune competent cells at the fetomaternal interface. There are many different interactions between the endocrine and immunological system. Hormones modulate the secretion of certain cytokines and vice versa. In reproductive medicine it is of specific interest to evaluate these functions for treating problems during the early pregnancy.

Genital findings in sexually abused prepubertal girls. Childhood sexual abuse is defined as the involvement of dependent, developmentally immature children and adolescents in sexual activities that they do not fully comprehend, to which they are unable to give informed consent or that violate the social taboos of family roles. Essential to the diagnosis of sexual abuse is an awareness of the problem and acknowledgement of its manifestations. The evaluation of the sexually abused girl usually is performed in a pediatric and adolescent gynecology outpatient department. Thus, the gynecologist will be part of a multidisciplinary approach to the problem and will need to be competent in the basic skills of history taking, physical examination, selection of laboratory tests und differential diagnosis. Findings secondary to sexual abuse are often subtle. Acute tears or bruisings are rare, because force is seldom part of sexual acts committed against a child. A vaginal opening of greater than 5 mm is not common and may indicate vaginal penetration. An intact hymen not necessarily exclude vaginal intercourse. Lack of physical evidence never rules out abuse because sexual acts may leave no physical findings. Language: de

The histologic status of the regional lymph nodes draining the site of a malignant tumor is signifikant for the patient's prognosis. But for most gynecologic malignancies, particularly early stage lesions, the therapeutic benefit of lymphadenectomy is unclear. From a physiologic standpoint, removal of negative lymph nodes can be considered a reduction of immunocompetent tissue and might compromise the immunologic response. Can the prognostic information provided by the lymph node status also be gained through detailed pathomorphology of the primary tumor? Is lymphadenectomy justified for all gynecologic malignancies? We review the current status of lymphadenectomy in gynecologic cancer.

In endometriosis urinary tract involvement occurs in about 1 percent. While bladder involvement is more common, ureteral endometriosis can contribute to hydronephrosis and renal failure. We here report on two cases of ureteral endometriosis diagnosed due to hydronephrosis. In both cases we first relieved the kidney in placing a percutaneous nephrostomy tube into the renal pelvis. Then a laparotomy with resection and reimplantation of the ureter was performed. In one patient a resection of a segment of the rectum was also necessary because of excessive endometriosis. This patient was treated pre- and postoperatively with GnRH-agonists.

A possible link between protein kinase C (PKC) and P-glycoprotein (P-gp)-mediated-multidrug resistance (MDR) was assumed from studies on MDR cell lines selected in vitro. The functional relevance of PKC for the MDR phenotype remains unclear, and the involvement of a particular PKC isozyme in clinically occurring drug resistance is not known. Recently, we have demonstrated significant correlations between the expression levels of the PKC eta isozyme and the MDR1 or MRP (multidrug resistance-associated protein) genes in blasts from patients with acute myelogenous leukaemia (AML) and in ascites cell aspirates from ovarian cancer patients. To extend these findings to further types of human tumours we analysed specimens from 64 patients with primary breast cancer for their individual expression levels of several MDR-associated genes (MDR1, MRP, LRP (lung cancer resistance-related protein), topoisomerase (Topo) II alpha/IIbeta, cyclin A and the PKC isozyme genes (alpha, beta1, beta2, eta, theta, and mu) by a cDNA-PCR approach. We found significantly enhanced mean values for MRP, LRP and PKC eta gene expression, but significantly decreased Topo II alpha and cyclin A gene expression levels in G2 tumours compared with G3. Remarkably, significant positive correlations between the MDR1, MRP or LRP gene expression levels and PKC eta were determined: MDR1/PKC eta (rs = +0.6451, P < 0.0001) n = 62; MRP/PKC eta (rs = +0.5454, P < 0.0001) n = 63; LRP/PKC eta (rs = +0.5436, P < 0.0001) n = 62; MRP/LRP (rs = +0.7703, P < 0.0001) and n = 62, MDR1/MRP (rs = +0.5042, P < 0.0001) n = 62. Our findings point to the occurrence of a multifactorial MDR in the clinics and to PKC eta as a possible key regulatory factor for up-regulation of a series of MDR-associated genes in different types of tumours. Images Figure 1

We report on a 60 year old patient with a 6 month history of vulval pruritus and an erosive vulval lesion which was mistaken for lichen sclerosus et atrophicus. Histologically the diagnosis of an amelanotic malignant melanoma of the vulva was established. We review the literature about this rare malignant tumor.

Background: In the general population, uterine sarcoma (US) is an uncommon tumor, which accounts for approximately 1–3% of all uterine neoplasms. Its biological behavior is characte

A severe hepatopathy constitutes a serious threat during pregnancy and poses considerable challenges to the treating physicians. A broad spectrum of pregnancy-dependent or independent diseases like HELLP-syndrome, liver infection or acute fatty liver of pregnancy (AFLP) is characterized by these affections of the liver. In this study, we present a series of 3 cases with life-threatening hepatopathies and discuss the current state of the literature. A special focus is placed on pathogenesis and differential diagnosis.Pathological, radiological and gynaecological/surgical procedures were performed according to the current German guidelines. Laboratory tests were conducted in the clinics' routine diagnostics section. The existing literature was reviewed via the US National Library of Medicine database “PubMed.gov”.The first patient had been afflicted by a fulminant HELLP syndrome causing delivery after 32 weeks of pregnancy. Consecutively, she suffered a sub-total liver infarction followed by a severe coagulopathy and septic peritonitis. The second patient was diagnosed with HELLP syndrome at 36 weeks of pregnancy. The initially mild syndrome exacerbated after delivery leading to haemorrhagic shock and acute renal failure. In the third case, a woman with asymptomatic hepatitis B delivered in the 36th week of pregnancy. Post partum, her pre-existing condition worsened fulminantly resulting in sub-acute liver dystrophy and massive coagulopathy.Whenever a hepatopathy occurs during pregnancy, several divergent diagnoses with severe implications and different aetiopathologies have to be considered. Diagnostic and therapeutic strategies have to be weighed quickly to enable a fast, interdisciplinary cooperation in order to prevent fatal outcomes.

The perinatal morbidity and mortality risk in monochorionic twin pregnancies are 3-5-fold increased compared to those of dichorionic twin pregnancies. Partially, this is due to the higher rate of preterm delivery but also to the twin-to-twin transfusion syndrome (TTTS). Caused by unidirectional blood flow via placental anastomoses, the TTTS leads to weight differences of more than 20% between monochorial twins. The blood donor often shows oligohydramnios, whereas the recipient shows polyhydramnios. Lewi et al. demonstrated, in a study with 202 monochorionic twin pregnancies, a 9% rate of severe TTTS. The mortality of this complication is about 90% when untreated. In contrast to the chronic TTTS, little is known about the acute intrapartal one, which is characterised by anaemia and hypovolaemia of the donor and polyglobulia of the recipient without significant weight differences between the two. In most cases, anaemia occurred after normal delivery of the first twin. Still, there are no means or signs for early detection. We describe the case of a 30-year-old primigravida with a monochorionic diamniotic twin pregnancy. During pregnancy, no evidence of TTTS could be detected. At 37 + 1 weeks gestation labour was induced with prostaglandin-containing gel. Both foetuses showed cephalic presentation. The CTG of the first twin showed a conspicuous heart rate. After labour the first twin presented with anaemia and hypovolaemic shock, the APGAR was 2/7/8. The infant's haemoglobin was 13.7 g/dL. After delivery, the second twin with APGAR 10/10/10 showed a haemoglobin of 19.6 g/dL, which is in the upper normal range. Their birth weights differed by merely 10.4%. Acute TTTS is frequently characterised by anaemia and hypovolaemia of the second twin. In our case of a monochorionic twin delivery with acute TTTS the donor was born first. Early diagnosis and neonatal intervention is essential for reducing postnatal morbidity and mortality.

AEZS-115 (Aeterna Zentaris GmbH, Frankfurt/M, Germany) is an orally active peptidomimetic antagonist of gonadotropin-releasing hormone (GnRH). In various tumors, an autocrine growth-promoting loop has been described for GnRH. The current study evaluates the antitumor activity and mechanism of action of AEZS-115 in models of ovarian and endometrial cancer.Human A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells were analyzed for GnRH receptor expression by reverse transcription polymerase chain reaction (RT-PCR). These cell lines were incubated with AEZS-115 at 1, 10 and 100 μM for 24 h, 48 h, and 72 h and the number of viable cells was determined. Fluorescence activated cell sorting (FACS) cell cycle analyses were performed with increasing concentrations of AEZS-115. Co-treatment experiments of cancer cells with GnRH antagonist cetrorelix and peptidomimetic GnRH antagonist AESZ-115 were carried out.A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells expressed GnRH receptors as demonstrated by RT-PCR. GnRH antagonist AEZS-115 inhibited growth of all cell lines in a dose- and time-dependent manner. Half maximal inhibitory concentration (IC(50)) values at 48 h of incubation were between 7 and 17.5 μM and for 72 h between 4.5 and 12.5 μM. IC(50) values for ovarian and endometrial cancer cells were rather similar. These results were obtained by tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay and confirmed by additional crystal violet staining. Cell cycle FACS analysis revealed that AEZS-115 dose-dependently increased the fraction of apoptotic cells. Co-treatment experiments carried out with AEZS-115 and peptidic GnRH-antagonist cetrorelix suggest that the antitumor effect of AEZS-115 is not mediated by blockade of the GnRH receptor.GnRH antagonist AEZS-115 exhibited substantial antitumor activity in ovarian as well as endometrial cancer cell lines. However, this antitumor effect was not mediated by the tumoral GnRH receptors. To identify the mechanism of action of this compound, further research is warranted. Its in vitro antitumor activity makes AEZS-115 a promising candidate for in vivo studies of ovarian and endometrial cancer.

Malformations of the central nervous system are among the most frequent congenital anomalies. At best, a qualified and standardised screening of the foetal brain is possible between the 18th and the 22nd week. The newly decided modification of the maternity directives envisages an extended screening upon request. This extended screening refers to the central nervous system and the representation of the ventricles, the evaluation of the head shape and the cerebellum and the back. The examination of the foetal brain should be carried out in a structured way. Three axial planes, the transventricular, the transthalamic and the transcerebellar planes, suffice to represent and measure all structures which are of importance for the screening. In case of ventricular anomalies, anomalies of the head shape, anomalies of the cerebellum and irregularities of the dorsal skin outlined in the second screening a further diagnostic procedure should be initiated. This diagnostic work-up should include a detailed neurosonography, a diagnostic evaluation of the organs and eventually further examination in the form of a caryotyping, determination of the infectology or a foetal MRI. The present article offers an overview of possible CNS abnormalities which could be recognised during the second screening according to the extended maternity directives and describes which differential diagnostics should be considered. In detail, anomalies of the head size (microcephaly, macrocephaly), of the head size (brachycephaly, dolichocephaly, cavities of the cranium, banana sign, etc.,), ventricular abnormalities, anomalies of the cerebellum (cerebellum hypoplasia, abnormal cerebellum shape) and abnormalities of the intermediate line and the intracerebral space requirements are discussed.

The current study investigates if an inductive method for the generation of ethical principles can be applied to the crucial moral question if late interruption of pregnancy due to fetal disease is ethically adequate.This method originates from the US American philosopher John Rawls and puts a group of so-called competent moral investigators in the beginning of the decision process. These competent moral investigators should be objective, tolerant and sensitive. Thus, real cases which lead to an intuitive, unanimous and clear decision of the competent moral investigators are analysed for the underlying ethical principles. The ethical principles thus detected are then applied to more complicated cases which could not be assessed clearly.In the current study, the case of foetal trisomy 18 and foetal palate cleft could be clearly judged with a yes and a no, respectively, with regard to an approval of late interruption of pregnancy. The underlying ethical principle leading to these decisions is the utilitaristic principle of minimising harm for mother and fetus.We then tried to apply this principle to a case of foetal trisomy 21, however, no clear decision for an approval or a disapproval of the interruption of pregnancy could be found as it was not possible to assess foetal interests.

The anatomy of the ilioinguinal nerve makes it vulnerable to entrapment near its exit from the superficial inguinal ring, where it lies almost directly superior to the pubic tubercle. Ilioinguinal nerve entrapment is a documented complication of inguinal herniorrhaphy, inguinal lymph node dissection, appendectomy, Pfannenstiel incision and the needle suspension procedure. It has not previously been described as a complication of the tension-free vaginal tape (TVT) procedure, which is the most recent technique for the treatment of genuine urinary stress incontinence. This paper describes a clinical history to illustrate the diagnosis and management of ilioinguinal nerve entrapment occurring as a complication of tension-free vaginal tape procedure.

Obstetrics services in Europe are dominated by a persistently low birth rate, the average number of children born to a woman in her lifetime now being 1,45 for the European Community in general. This low rate has persisted for the last 20 years. During the past 10 years, childlessness has been steadily increasing. Maternal age at first delivery has also increased. Obstetric departments are increasingly subject to market principles and the trend towards centralization, which has been developing for some years, will continue.

Acute myocardial infarction during pregnancy is a rare event that is often associated with a very high maternal mortality, estimated to be from 19 to 37%. During the last decades the incidence of myocardial infarction during pregnancy has increased . The main contributing factor could be a higher prevalence of the metabolic syndrome. The strongest predictors correlated with a myocardial infarction are hypertension, diabetes mellitus and advanced maternal age. In addition, improved diagnostic tools could explain the elevated incidence of myocardial infarction during pregnancy. In general gestation is not considered a risk factor for myocardial infarction but gravidity is accompanied by an increase in oestrogen and progesterone levels. It is generally accepted that oral contraceptives increase the risk of coronary heart disease. We present a case where a 37-year-old gravida was admitted to hospital with diffuse thoracic pain. In the patient's history, we found several putative reasons for the thoracic pain that pointed to a musculoskeletal cause. Based on an elevation of ischaemic heart markers and continuous non-specific thoracic pain we performed a primary Cesarean section. In the coronary angiography procedure that followed, a thrombotic occlusion of the ramus diagonalis was diagnosed. We here describe the differential diagnosis as well as the problems associated with diagnosing myocardial infarction in the third trimester of pregnancy.

Pleomorphic adenoma (PA) is a benign mixed tumor found commonly in the salivary glands but rarely in the breast. PA might be misinterpreted clinically and pathologically as a malignant tumor. The differential diagnoses include fibroadenoma, phyllodes tumor and metaplastic carcinoma. Metaplastic carcinoma is the most important entitiy with respect to differential diagnoses, as surgical overtreatment, i.e., mastectomy may be the result. We describe one of the first cases of PA initially misdiagnosed as metaplastic carcinoma (osteoid-chondroid type) in a preoperative stereotactic biopsy and review the literature regarding this entity.

Gestational diabetes mellitus (GDM) occurs in 3-5% of all pregnant women. As there is no general screening in Germany, many cases remain undetected. Maternal as well as foetal morbidity are increased in GDM. The aim of this study was to investigate whether amniotic fluid insulin or C-peptide levels, collected by genetic amniocentesis in early pregnancy, are predictive for gestational diabetes. Patients at risk for developing GDM might be identified and treated very early.260 patients having a genetic amniocentesis were included in this prospective trial. Insulin and C-peptide levels were identified in frozen amniotic fluid samples. All patients should undergo an oral glucose tolerance (oGTT) test at 24-28 weeks of gestation. Only cases with normal genetic screening, normal foetal sonomorphology and birth at term were included in this trial. 90 of 260 patients having an amniocentesis underwent the oGTT and fulfilled all inclusion criteria.GDM was diagnosed in 8 patients, in another 6 patients only one glucose level was out of the normal range. Neither amniotic fluid insulin nor C-peptide levels showed significant differences between normal and GDM pregnancies. The insulin and C-peptide levels did not correlate with blood glucose levels or with foetal weight.In contrast to literature reports, according to these data no relationship between amniotic fluid insulin or C-peptide levels and gestational diabetes can be assumed. Amniotic fluid insulin or C-peptide levels are not predictive for GDM.

Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment.

The diagnostic value of cystoscopy and intravenous pyelography in the staging of carcinoma of the corpus uteri was evaluated in a retrospective study of 218 patients. The primary treatment in all patients was surgical. Cystoscopy was performed preoperatively in 71 (33%) of the patients and postoperatively in 90 (41%); 57 (26%) patients were not subjected to this investigation. Intravenous pyelography was performed in 95 (44%) of the patients and postoperatively in 70 (32%); 53 (24%) patients were not subjected to this investigation. In no patient did cystoscopy reveal invasion of the bladder by tumor. In one patient with a stromal sarcoma (stage IV), there was no flow of dye through the ureteral orifices. Intravenous pyelography revealed unilateral ureteral obstruction in one case of stromal sarcoma (stage III) and complete bilateral ureteral obstruction in another case (stage IV). These findings show that cystoscopy and intravenous pyelography are unnecessary in carcinoma of the corpus uteri at stages I and II, and that in stages III and IV the necessity for these investigations should be considered for each patient on an individual basis.