[BRCA diagnostics of ovarian cancer : Molecular tumor testing since the introduction of PARP inhibitor therapy]. / BRCA-Diagnostik an Ovarialkarzinomen : Molekulare Tumortestung seit Einführung der PARP-Inhibitortherapie.

Approximately 9000 women are diagnosed with ovarian cancer in Germany each year. The most common subtype is high-grade serous ovarian cancer. A relevant proportion of these tumors are associated with mutations in the breast and ovarian cancer susceptibility genes (BRCA1 and BRCA2) representing highly penetrant tumor suppressor genes with autosomal inheritance and play a crucial role in DNA repair mechanisms. These patients have predominantly germline mutations and less frequently have somatic BRCA mutations. Tumors harboring BRCA mutations show a significant improvement in progression-free survival under therapy with poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. In 2015 the first PARP inhibitor was approved for the therapy of high-grade serous ovarian cancer with BRCA mutations. Mutation analysis can be performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue within a few days.

[Schwannoma in the epipharynx: a rare differential diagnosis]. / Schwannom im Epipharynx: Eine seltene Differenzialdiagnose.

There are many benign and malignant tumors of the epipharynx, which makes differential diagnosis difficult. As a very rare differential diagnosis, a schwannoma is possible. The origin of the tumor is most likely a small branch of a sensitive nerve of the glossopharyngeal nerve or the trigeminus nerve. A clear differentiation in the MRI scan is often not possible; especially differentiation from MPNST (malignant peripheral nerve sheath tumors) is difficult. To confirm the diagnosis and exclude malignancy, every tumor in the epipharynx should be surgically excised if possible, even if the patient has no discomfort.

Uterine activity monitoring during labour--a multi-centre, blinded two-way trial of external tocodynamometry against electrohysterography.

PURPOSE: The aim of this study was to determine the quality of intrapartum uterine activity (UA) monitoring in daily practice during the first and second stages of labour. The total duration of inadequate UA monitoring is quantified in relation to the technique applied, namely, external tocodynamometry (TOCO) or electrohysterography (EHG). MATERIAL AND METHODS: 144 UA recordings, collected from 1st September 2008 until 15th October 2009 from deliveries at the Marien-Hospital Witten, Germany, were analysed by obstetricians based at different centres. The included recordings were from singleton and simultaneously with external TOCO and EHG monitored pregnancies. External TOCO and EHG UA recordings were blinded. RESULTS: The percentages of "adequate" UA recordings in the first and second stages of labour were much higher for the external EHG than the external TOCO mode (p<0.001). All doctors evaluated the UA assessment as "easier" (p <0.001) using the EHG compared with TOCO. CONCLUSION: Intrapartum UA monitoring in -daily practice via the EHG mode provides a more recognisable UA trace than the TOCO.

[Alcohol and pregnancy--embryopathy and alcohol effects]. / Alkohol und Schwangerschaft--Embryopathie und Alkoholeffekte.

Fetal alcohol syndrome (FAS) is a specific polydystrophic pattern of malformations with the following diagnostic criteria: 1. Maternal alcohol dependence or alcohol abuse during pregnancy. 2. Pre- and postnatal deficiency of growth in weight, height and head circumference. 3. Multiple minor and major anomalies recognizable mainly at a typical face. 4. Structural injuries and changes at the central nervous system with complex brain dysfunction combining elements of cognitive impairments, behavioral disturbance and neurological damage. Fetal alcohol effects (FAE) or so-called "alcohol-related neurodevelopmental disorders" (ARND) with predominant neurotoxic effects and a large spectrum of cerebral dysfunctions are manifold more frequent than the full-blown FAS. These remain mostly unrecognized, overlooked and they are difficult to be diagnosed, the symptoms being unspecific. Alcohol in pregnancy is nowadays the most important and the most frequent toxic substance for the embryo and the fetus and one of the most frequent causes of mental retardation. The longlasting and irreversible consequences refer to school development, social maturation, social behaviour and later life-style. The diagnosis is based on the careful maternal history and on the clinical findings; there are no biochemical parameters of assessment. The risk of addiction development in these children is assumed to be more than 20 percent.

Fetal alcohol syndrome (FAS) in dermatology: an overview and an evaluation.

Certain skin disorders are affected by alcohol abuse. Maternal alcohol abuse during pregnancy also gives rise to a typical malformation pattern in the child with a varying degree of severity (grade I-III). The diagnosis of fetal alcohol syndrome (FAS) is based on the detailed history of the maternal alcohol consumption in combination with the clinical, morphological, intellectual and psychosocial development of the child. The behavior of the child is also of diagnostic value. The grade of severity of the FAS can be determined during the first three years of life on the basis of a scoring system. In addition to medical care and surgical treatment of associated disorders, early support for the mental development of the child is of immense importance. Furthermore, the medical, social and psychological care of the mother must be considered. In the field of dermatology, knowledge about the pathomechanism of FAS is also important for its prevention in unborn children. Women of childbearing age presenting with dermatological signs of possible alcohol abuse, should alert the dermatologist to the possible risk to the child of FAS. Familiarity with FAS and the ability to recognise its clinical features are important for the adequate treatment and support of the affected child and for the mother suffering from alcohol disease, in cooperation with other treating doctors.

[Fetal alcohol syndrome in adulthood. A long-term study]. / Alkoholembryopathie im Erwachsenenalter. Eine Langzeituntersuchung.

BACKGROUND AND OBJECTIVE: Maternal alcohol addiction in pregnancy causes fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) in children. At present, little is known about the physical, mental, and social long-term consequences in adulthood. PATIENTS AND METHODS: Since 1974, 52 children with FAS and FAE, all born to alcohol dependent mothers, were prospectively followed up from birth to adulthood. Height, weight and head circumferences were based on percentile standards; mental and school development were assessed by school reports and by intelligence subtests. By structural interviews, occupational and social follow-up were assessed. RESULTS: Growth retardation continued mainly in severely affected adults with underweight in 26%, underheight in 30%, and microcephaly in 46%. They mostly lived in foster families, only 6/52 were able to live independently. In 56% special schools for handicapped and mentally disabled were attended. In most cases (37/52), simple occupations without vocational training were practised. CONCLUSIONS: It is mainly the neurotoxic effects of alcohol in pregnancy that have longlasting developmental significance in adults. Because of the dysmorphic changes over time, it is difficult to diagnose FAS and FAE only in adulthood.

Lectin-induced increase in clonogenic growth of haematopoietic progenitor cells.

The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p < 0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with D-galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation.

Polarity reversal improves defibrillation efficacy in patients undergoing transvenous cardioverter defibrillator implantation with biphasic shocks.

The purpose of this study was to determine the influence of polarity reversal on DFT in patients undergoing implantation of nonthoracotomy defibrillators with biphasic shocks. Previous studies have shown higher defibrillation efficacy with using the distal electrode as anode implantation of nonthoracotomy defibrillators and monophasic shocks. However, it is as yet unclear whether biphasic shock defibrillation will also be influenced by polarity reversal. Using a transvenous lead system with a proximal electrode in the superior caval vein and a distal electrode in the RV apex, 27 patients undergoing defibrillator implantation were randomized to DFT testing "initial" (distal electrode = cathode) or "reversed" polarity (distal electrode = anode). Defibrillation energy was reduced stepwise until defibrillation failure occurred. At this point, polarity was switched and testing continued until the lowest energy requirement was determined for both polarities. With reversed polarity, DFT was 11.1 +/- 5.7 J versus 13.3 +/- 5.8 J with polarity (P = 0.033). This means a 17% reduction of the DFT. In 10 patients, the threshold was lower with reversed, whereas in 3 patients it was lower with initial polarity. In conclusion, changing electrode polarity in transvenous implantable defibrillators with biphasic shocks may significantly influence defibrillation energy requirements. Therefore, polarity reversal should always be attempted before considering patch implantation.

Congenital heart disease in the 48,XXYY syndrome.

We report on an infant with severe tetralogy of Fallot, bilateral preauricular pits, and a 48,XXYY chromosomal complement. This case and evidence collected from the literature suggest that congenital heart disease may occur in the 48,XXYY syndrome more frequently than currently appreciated.

[Pulmonary varicose veins. Case report and review of the literature]. / Pulmonalvenenvarikose. Fallbeschreibung und Literaturübersicht.

Pulmonary varicosis is a rare, presumably congenital localized dilatation of a pulmonary vein which is often associated with cardiac disease. We describe a case featuring enlargement of a pulmonary varix after mitral valve replacement, caused by mitral regurgitation, and discuss diagnostic possibilities, differential diagnosis and various development of this vascular malformation. A detailed review of the literature is given.

[Alcohol in pregnancy and fetal heart damage]. / Alkohol in der Schwangerschaft und kindliche Herzschäden.

Alcohol abuse and addiction during pregnancy can induce damage of the heart muscle and heart defects in the offspring. Between 1973 and 1991 216 children with fetal alcohol syndrome were diagnosed and examined for congenital heart defects. In 63 children (= 29,1%) heart defects were present, established mainly by heart catheterization and/or echocardiography. Most frequently ventricular septal defects (24/63) and atrial septal defects (23/63) occurred, less frequent were AV-defects (3), PDA (3), Fallots teralogy (5), and other malformations (5). Biopsy during heart surgery in 3 children revealed histological and electron microscopic changes of alcohol-cardiomyopathy. Heart defects are predominantly found in children with higher degree of severity concerning the clinical syndrome, less frequently in alcohol effects (4/38 = 11%). Alcohol in pregnancy, even in the course of so called social drinking, usual drinking and binge drinking has to be considered as an essential and preventable co-factor within the multifactorial etiology of congenital heart defects.

[Eye manifestations of fetal alcohol syndrome]. / Augenveränderungen bei Alkoholembryopathie.

Alcohol is the most frequent and most important teratogenic agent causing mental and physical retardation in childhood. The alcohol fetal syndrome is characterized by pre- and postnatal growth retardation, hypotonia, hyperactivity, microcephalus, mental retardation and typical craniofacial malformations. The latter includes short palpebral fissures, a poorly developed philtrum, thin upper lip vermillion, short mandibles, a flattened midface structure and dysplastic ears. Ophthalmological signs occur in 90% and include epicanthus, ptosis, myopia, optic nerve hypoplasia and tortuous retinal vessels. Microphthalmus, coloboma and Peters' anomaly have also been described. Five children with alcohol embryopathy are presented. The histopathological findings of the enucleated eye of a 6th child with alcohol embryopathy which was sent to us for examination and which revealed an anterior staphyloma with Peters' anomaly is also described. Ophthalmologists should be aware of alcohol in pregnancy as a preventable cause of eye malformation.

[Are children with alcohol embryopathy latent alcoholics? A study of the risk for developing dependence]. / Sind Kinder mit Alkoholembryopathie trockene Alkoholiker? Eine Untersuchung zum Risiko der Suchtentwicklung.

Within 3 years 48 caretakers and parents of children with fetal alcohol syndrome were asked about the childrens experience and contact with alcohol. The children were mainly raised in foster and adoptive families (40/48 cases), where usually moderate or restricted consumption of alcohol was common. The children were between 4-18 years (means = 7; 5) of age. In 5 children alcohol consumption was observed once or several times. Some children showed signs of increased desire for drinking alcohol. A substance related addiction was never observed until now. Nevertheless the risk of addiction development has to be considered as dangerous in any case of fetal alcohol syndrome. All conditions and risk factors for addiction development are present: a) Hereditary factors in the family of origin. b) Early use and adaption in the prenatal period by maternal drinking. c) The social surroundings and family. d) The particular structure of personality in these children, characterised by uncritical behavior, mental retardation, emotional instability and easy seduction. The risk of addiction development can be estimated to 30%. In a society of lacking alcohol prohibition it will be impossible to keep alcohol away from the children. As in dry alcoholics the children have to learn "to live in association with alcohol without drinking it". Besides it is important for the parents, that they learn to help their child to cope with the danger of alcohol. This ist possible by means of information, strengthening of a positive self-image and faith in the child's capacity for insight.

[Mild forms of alcoholic embryopathy following excessive use of alcohol]. / Schwachformen der Alkoholembryopathie nach exzessivem Alkoholgenuss.

Within 15 years 171 children with fetal alcohol syndrome were diagnosed. Eight children showed an unusual low susceptibility to the harmful effects of alcohol in utero with mild expression of fetal alcohol syndrome or so-called alcohol effects, inspite of excessive maternal drinking (more than 180 gs alcohol per day). Increased tolerance of alcohol might be explained by two mechanisms: 1. By metabolic adaptation, mainly by swift increase of alcohol metabolizing; 2. by biochemical and structural adaptation at cellular membranes after chronic alcohol ingestion. The grade of severity in fetal alcohol syndrome does not depend on the amounts of alcohol but mainly on the development of metabolic and morphological tolerance and adaptation.

[Congenital alcoholic cardiomyopathy in 3 children]. / Konnatale Alkoholkardiomyopathie bei drei Kindern.

Three cases of congenital alcoholic cardiomyopathy and cardiac defects in children are described. The mothers were heavy spirits drinkers. One child had a ventricular septal defect, two had Fallot's tetralogy, all requiring operation. At open-heart surgery left-ventricular myocardial biopsies were obtained in all three children. Histological and electronmicroscopic examination revealed primary toxic and hypotrophic changes, which differed from those seen in alcoholic cardiomyopathy of the adult. The cells, their nuclei and the myofibrils had reduced diameters. The mitochondria were damaged to differing extent. The myofibrils were arranged in parallel and some had contraction bands and ruptures. The sarcoplasmic reticulum was dilated and had vacuoles. The cell surface penetrated into the interstitial tissue. All these changes could have resulted from inhibited embryofetal cell growth and cytotoxic damage by alcohol during pregnancy. It would seem that alcoholic cardiomyopathy occurs only in extreme forms of alcohol abuse during pregnancy. The prognosis is as yet unknown.

Comparison of analytical predictions and verification flight test results for the performance of the Spacelab environmental control and life support subsystem as obtained during the 1st mission.

The environmental control and life support subsystem (ECLS) of the Spacelab module provides various functions which can be assigned to its various branches as follows: Thermal insulation from the external environment is achieved by the passive thermal control subsystem (PTCS). Rejection of the heat produced by the Spacelab subsystem equipment and by the various experiments is the task of the active thermal control subsystem (ATCS). Life support in the form of cabin air ventilation, oxygen/carbon dioxide partial pressure control; total pressure and air temperature/humidity control is achieved by the life support subsystem (LSS). In the first part of the paper a brief description of the various elements and loops forming the Spacelab ECLS will be given by discussing the PTCS, ATCS and LSS in some detail. Objective of the verification flight test program--as implied in the title already--is the verification of major requirements the ECLS has to comply with. Those requirements will then be comprehensively discussed in the second part of the paper. A description of the analytical approach is given in the third part of the paper. However, only those areas will be addressed which were included in the verification flight test program. A brief description of the flight instrumentation, the data transmission and collection follows then in the fourth part of the paper. In the fifth part of the paper the approach to select and compile flight test data obtained during the first mission (Shuttle flight STS 9) from November 28 till December 8, 1983 is illustrated. Flight test data are compared with the analytical predictions in form of examples. In the sixth and last portion of the paper the actual/measured performance is compared with the requirements, and conclusions are drawn with respect to comprehensiveness/accuracy of the flight test verification and the compliance of the Spacelab actual performance with the requirements.

Surgery of coarctation of the aorta: a nine-year review of 253 patients.

From 1973 to 1982, 253 patients--164 males and 89 females--underwent an operation for coarctation of the aorta in our clinic. Of the patients 72.3% presented with a circumscribed lesion and 58.5% with associated congenital cardiovascular defects. Resection with end-to-end anastomosis was performed in 138 patients (54.5%). Seventy-four patients (29.3%) had vascular graft prosthesis, 1.2% underwent the Clagett's operation, 9.1%, the indirect isthmoplasty and the rest (5.9%), the subclavian flap plastic. Ventricular fibrillation led to the intraoperative death of 3 infants with associated intracardiac and multiple somatic defects. The operative mortality was high in children under 15 months (13.2%), 1% in all the others taken together and 0% in all cases without concomitant lesions. Paraplegia occurred in only one patients (0.4%). One hundred twenty-eight patients were followed-up over a mean period of 3.6 years. The systolic and diastolic pressures decreased by a mean of 30 mmHg and 15 mmHg respectively. Eighty-seven patients (68%) had normal blood pressure at the time of examination. The rest (41 patients) had persistent postoperative hypertension necessitating medical management. The surgical technique elected did not influence the level and incidence of persistent postoperative hypertension, rather the level of the preoperative systolic right arm-to-leg pressure gradient (SPG) related closely to the incidence of persistent hypertension. Thirty patients (23.4%), among whom were 24 children under 10 years--some of them with preductal hypoplasia--presented with an SPG above 20 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rupture of a coronary artery aneurysm in mucocutaneous lymph node syndrome (Kawasaki syndrome). Demonstration of the coronary aneurysms by 2-dimensional echocardiography]. / Ruptur eines Coronararterien-Aneurysmas bei mukokutanem Lymphknotensyndrom (Kawasaki-Syndrom). Darstellung der Koronaraneurysmen durch 2-dimensionale Echokardiographie.

A further case of mucocutaneous lymphnode syndrome (MCLS) in infancy with multiple aneurysms both of the coronary arteries and systemic arteries is presented. Aged four months the male infant died of rupture of an aneurysm of the right coronary artery causing a hemopercardium. The aneurysms both of the coronary and systemic arteries were diagnosed intra vitam by 2-dimensional echocardiography.