Cryopreservation of Ovarian Tissue: Detailed Description of Methods for Transport, Freezing and Thawing.

Purpose: In many cases cancer therapy leads to an irreversible reduction or even loss of ovarian reserve. Cryopreservation of ovarian tissue with subsequent thawing and re-transplantation of tissue after the cancer is in remission constitutes a promising method to preserve fertility in women. To date, more than 25 cases of live births after re-transplantation of cryopreserved ovarian tissue have been published worldwide. In Germany the first live birth after re-transplantation of cryopreserved tissue was in 2011. Material and Methods: After surgical removal of ovarian tissue in the Gynaecological Clinic of Dresden University, the tissue was sent to the Gynaecological Clinic of Bonn University in a special transport container at 5 °C and was frozen the next day using 1.5 M dimethyl sulfoxide cryosolution. In 2010 this ovarian tissue was thawed using a sucrose solution in the Gynaecological Clinic of Erlangen University Clinical Centre and was laparoscopically re-transplanted into the patient. Results: The patient became pregnant, the pregnancy was uneventful, and she gave birth to a healthy boy. Conclusion: Freezing of ovarian tissue with subsequent re-transplantation as described here is a viable method to preserve fertility in cancer patients.

Detection of autoantibodies to tumour-associated antigens in sera of patients with systemic autoimmunity using a novel protein microblot array.

It is well known that sera of patients with systemic autoimmunity contain autoantibodies to nuclear antigens. It is also known that patients with systemic autoimmunity have an increased risk for the development of tumours. Interestingly, tumour patients frequently develop autoantibodies and there is a growing list of potential tumour-associated antigens. It is, however, not known whether or not patients with systemic autoimmunity also develop antibodies to tumour-associated antigens. Here we describe the development of a novel multiprotein array allowing us to screen for autoantibodies to 30 different tumour-associated antigens in parallel. Using this novel assay, we found that the frequency of autoantibodies to the selected tumour-associated antigens is increased between 2- and 14-fold in patients with systemic autoimmunity compared with an age-matched control group.

[Fetal juvenile granulosa cell tumor with hermaphroditism verus - prenatal diagnosis, management and outcome]. / Fetaler juveniler Granulosazelltumor mit Hermaphroditismus verus - pränatale Diagnostik, Management und postnatales Outcome.

Fetal ovarian cysts are common during pregnancy and after delivery. Most of these cysts are simple cysts that involute during pregnancy or in the first months of life. However, complicated cyst with a heterogeneous structure and also possible and can result in various complications: rupture, hemorrhage, ascites, edema of the labia, compression of other viscera, and ovarian torsion. In this case report we describe rare diagnosis of a complicated fetal ovarian cyst with edema of the labia and moderate ascites. The neonate had ambiguous genitalia with clitoromegaly. The newborn underwent surgery with oophorectomy. During the operation a uterus with fallopian tubes was found. The pathological findings showed a juvenile granulosa cell tumor FIGO Ia. Karyotyping revealed a mosaic of 45, X/ 46, X mar (Y) in the peripheral blood as well as in the granulosa cell tumor. Because of a right side inguinal hernia, the child underwent a second surgery. Specimen taken from the abdominal gonad and the inguinal region showed testicular and dysplastic ovarian tissue. There were elevated levels of androgens in the child's peripheral blood due to the granulosa cell tumor. In summary, this case report describes a fetus with true hermaphroditism and a juvenile granulosa cell tumor diagnosed as a complicated ovarian cyst in the 32 (nd )week of pregnancy.

Which gynecological and obstetric patients want to attend psychosomatic services?

OBJECTIVE: The aim of this study is to explore the wish of gynecological and obstetric inpatients to attend psychosomatic services. Predictors influencing this wish are evaluated. METHOD: Three groups of patients participated in the study. The groups consisted of patients diagnosed with malignant gynecological diseases (n = 175), benign gynecological diseases (n = 302), and obstetric diseases (n = 238). The following domains were assessed in a cross-sectional design: symptoms of anxiety and depression (HADS), physical complaints (GBB-24), health-related quality of life (SF-12), and the wish to attend psychosomatic services. RESULTS: 34% of the participants indicated that they wanted to attend psychosomatic services during their stay in the hospital. The group of patients diagnosed with malignant gynecological diseases had the highest proportion of women who stated that wish (43%). Multiple logistic regression models showed that former psychotherapeutic experiences as well as low psychological quality of life predicted the wish to attend psychosomatic services in patients diagnosed with malignant gynecological or obstetric diseases. CONCLUSION: It was shown that a considerable proportion of patients wanted to attend psychosomatic care during their hospitalization. Contrary to physical and sociodemographic variables, psychological factors were significant predictors of the inpatient's wish to attend psychosomatic services. This suggests that the subjective estimation of impairments is a major predictor of the wish to attend psychosomatic care.

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial.

BACKGROUND: The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds. METHODS: We analysed postmenopausal women (mean age 64 years [SD 9]) with localised breast cancer randomly assigned to anastrozole (n=3125) or tamoxifen (n=3116). Efficacy measures, including death and risk-benefit indices, were analysed by intention to treat. Safety analyses were based on treatment first received (n=3092 for anastrozole and n=3094 tamoxifen). We calculated a risk-benefit analysis using the two global indices for the Women's Health Initiative and for Disease-Free Survival and Serious Adverse Events. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. FINDINGS: At median follow-up of 68 months (range 1-93), treatment-related adverse events occurred significantly less often with anastrozole than with tamoxifen (1884 [61%] vs 2117 [68%]; p<0.0001), as did treatment-related serious adverse events (146 [5%] vs 277 [9%]; p<0.0001) and adverse events leading to withdrawal (344 [11%] vs 442 [14%]; p=0.0002). Patients given anastrozole had significantly fewer overall events for the Global Index of the Women's Health Initiative (744 [24%] vs 851 [27%]; hazard ratio 0.85 [95% CI 0.77-0.94], p=0.001) and the Global Index of Disease-Free Survival and Serious Adverse Events (1453 [46%] vs 1594 [51%]; 0.88 [0.82-0.94]; p=0.0004). INTERPRETATION: Anastrozole is tolerated better than tamoxifen by postmenopausal women with early-stage breast cancer, and results in fewer serious adverse events. Furthermore, it has a more favourable overall risk-benefit profile and lower recurrence rate than tamoxifen.

Psychological and physical factors influencing the health-related quality of life of patients of a department of gynecology in a university hospital.

The aim of our study was to assess the physical and mental quality of life of in-patients of a Gynecological University Hospital and the factors influencing the quality of life. 715 women, who were treated in hospital with non-malignant or malignant gynecological or obstetrical diseases, took part in the study. Besides demographical data and relevant medical parameters the quality of life (SF-12), anxiety and depression (HADS) as well as physical discomforts (GBB) were assessed. The physical quality of life of the study population was significantly lower than that of the normal population (p < 0.001). Patients with obstetric diseases in comparison with patients with malignant gynecological and other gynecological diseases had the lowest physical quality of life. Regarding the mental factor, patients with malignant gynecological diseases feel most impaired, followed by those with other gynecological and obstetrical conditions. The multivariate analysis of the quality of life showed that up to 60% of the variance could be explained. The lowest variance elucidation was found in obstetrical patients in whom the physical complaints elucidated only a small part of the variance. Our results show on the one hand the high impairment of mental and especially of physical quality of life in women who are in hospital with gynecological or obstetrical diseases. On the other hand they show the great significance of the quality of life as an outcome parameter. These findings should be considered in gynecological in-patient treatments by using integrated psychosomatic care.

Chemiluminometric determination of tissue polypeptide antigen (TPA), cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) in comparison with vascular endothelial growth factor (VEGF) in follow-up of breast cancer.

Vascular endothelial growth factor (VEGF), tissue polypeptide antigen (TPA), cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were measured in 314 sera of breast cancer patients and in 58 sera of women without breast cancer. VEGF was determined using a sandwich enzyme immunoassay technique (ELISA) and the tumour markers TPA, CA 15-3 and CEA with an immunoluminometric assay (ILMA). The breast cancer patients were staged according to the TNM classification stages 0-IV (by UICC) in patient groups with a compatible prognosis. Median and range of each stage were investigated. The cut-off values (95th and 97.5th percentile of control group) of VEGF, TPA, CA15-3 and CEA were determined; sensitivities for each parameter and for all combinations of two parameters were investigated for these cut-offs and the receiver operating characteristic (ROC) curves were calculated. The differences between the control group and stages 0-3 were shown to be non-significant for CA 15-3 and CEA but significant for VEGF and TPA. Significant differences were found in stage 4 for VEGF and all three markers. The increase in sensitivity of VEGF from stage 0 to stage 3 and the decrease from stage 3 to stage 4 can be interpreted based on the role of VEGF in the angiogenesis. The quantification of VEGF could give additional information for selecting patients for systemic adjuvant therapy.

[Urinary incontinence--taboo during postmenopause]. / Harninkontinenz--Tabuthema in der Postmenopause.

Urinary incontinence affects 30-60% of all women in the postmenopause. More and more women want to remove the taboo attached to incontinence, because they do not accept the reduction in quality of life, social and domestic activities. Detrusor instability (urge incontinence) and/or urethral sphincter incompetence (genuine stress incontinence) are the principal mechanisms, which lead to involuntary urine loss in older women. It is quite evident that additional factors as hypoestrogenism and urogenital atrophy influence urinary incontinence. Since in the postmenopause urge incontinence combined with urogenital atrophy its found predominantly, pharmacologic therapy with anticholinergic drugs and estrogen replacement are generally effective. Surgical therapy should be restricted to older women with genital prolapse and/or stress incontinence. In genuine stress incontinence, estrogen replacement therapy can lead to subjective improvement, but urodynamic parameters do not change objectively.

A new screening test for toxicity testing of dental materials.

OBJECTIVES: The development of a micro plate assay for cytotoxicity testing of dental materials based on a bioassay using brine shrimp larvae (artemia salina) as sensitive organisms. METHODS: Brine shrimp larvae are commonly used for cytotoxicity assays in pharmacology. These larvae are sensitive to toxic substances. The ratio between dead larvae (no motility) and living larvae (high motility) in comparison to a control without any toxic substances is used to estimate the toxicity of the test solutions. The test materials (Arabesk((R)), Solitaire((R)), Pertac((R)) II, Tetric((R)), Herculite((R)) and the compomer materials Dyract((R)), Hytac((R)), Compoglass((R))) were polymerized and consecutively milled. After incubation of 1g in 4ml distilled water at 37 degrees C for 48h, the solid materials were separated by centrifugation. The solutions were equibrilated with NaCl to a salt content of 25g/l. Aliquots of 200microl were distributed in eight micro wells and 50microl of a artemia salina containing (n=8-14) solution were added to each well. As controls eight wells with 250microl salt solution containing a comparable number of brine shrimp were used. At baseline, after 2, 5, 24 and 48h, the dead shrimp were counted using a stereo microscope. Finally all shrimps were sacrificed using Na-acid (5%) and counted to get the number of shrimps per well. RESULTS: All compomers and Solitaire caused 100% brine shrimp lethality after 24h and showed significantly (p<0.01, signed rank test) higher toxicities than the remaining composites. With the exception of Pertac II, all composites showed significantly higher toxic values than the control. Pertac II did not show any differences from the controls used. CONCLUSIONS: This new technique has some advantages for toxicity testing of restorative materials, because it can quickly be carried out at low costs. The disadvantage is the high quantity of material used and the low sensitivity.

[Redox sensitive behavior of selenite in the presence of reactive oxygen species. Are there nonenzymatic direct reaction pathways]. / Zum redoxsensitiven Verhalten von Selenit in Gegenwart reaktiver Sauerstoffspezies. Gibt es nichtenzymatische direkte Reaktionswege?

From extensive research over the last decade it has been known that selenium is essential as necessary component of selenoaminoacids and of specific enzymes. Among others, the redoxpair GSH/GSSG is closely connected with antioxidative processes. Moreover it inhibits and/or activates molecular key reactions with the involvement of various small reactive O- and N-species. We investigated the direct interaction of selenite with components of the respiratory burst of human blood cells, considering the redoxamphoterie of alkali-selenite. Selenite tend to redox-disproportation depending on the pH-value. Whether selenite leads to oxidation or reductation is dependent not only on the pH-value, but also on the redox-potential of the reaction partners. In in-vivo adapted in-vitro conditions (ph = 7.4; mumolar concentrations of reaction partners) we observed the following results: 1. SeO3(2-) is not oxidized by H2O2/NO or triplet-oxygen, when the oxidatives are applied alone; 2. SeO3(2-) is quantitatively oxidized from SeO4(2-) by the combination H2O2/NO2- or O2-/NO; 3. SeO3(2-) is semiquantitatively oxidized by singlett oxygen to SeO4(2-). The composition of reaction products was measured by 77Se-NMR-spectroscopy. The reactive intermediate product for the 2. reaction should be peroxynitrite (HOONO). One cannot rule out the possibility that HOONO reacts on a large scale with H2O2 to singlett oxygen. Subsequently singlett oxygen oxidizes selenite. The pathophysiological impact of singlett oxygen in processes like arteriosclerosis is now being investigated. It has been supposed, that singlett oxygen is participating in processes of lipidperoxidation invivo. Further investigations have to show, to what extent selenite is effective as direct 1O2-scavanger.

[Hyperthyroidism and acute renal failure in partial bladder mole]. / Hyperthyreose und akutes Nierenversagen bei partieller Blasenmole.

We report on a 31-year-old II gravida I para treated because of a hydatidiform mole, hyperthyroidism and acute renal failure in the 16th week of pregnancy. The pathomechanism of trophoblast-induced hyperthyroidism will be discussed. To our knowledge this is the first report on acute renal failure in association with trophoblast-induced hyperthyroidism.

Elution parameters and HPLC-detection of single components from resin composite.

The toxic effects of mercury derived from amalgam fillings have been a focus of controversy in Germany during the last 25 years. As alternatives to amalgam, composites are used widely to restore anterior and posterior permanent teeth. This study quantifies the amount of TEGDMA and methacrylic acid that can be derived from a polymerized commercial hybrid composite material. Different specimens were made with different curing methods with and without an oxygen inhibition layer. To simulate the removal of composite fillings, some samples were pulverized. The specimens were eluted in distilled water at 37 degrees C for different time intervals. To check the influence of acid conditions, pulverized material was incubated in 6 M HCl. The separation of the eluted chemical resin components was done by HPLC. A defined mixture of pure components was used as an external standard for the identification and quantification of the eluted components. The results focus on the release of triethylengly-coldimethacrylate (TEGDMA) and methacrylic acid. Concerning the different incubation methods, the results showed higher TEGDMA elution with oxygen inhibited surface layer and with the pulverized samples. Within acid conditions, the amount of TEGDMA found was low, but the amount of methacrylic acid increased. Small resin monomers like TEGDMA are primarily eluted from composite in aqueous solutions. Within acid conditions a hydrolytic disintegration of the ester bonding of the monomers could be observed. Methacrylic acid--a substance with allergenic potential--could be detected.

[Fetal acidemia and neonatal encephalopathy]. / Fetale Azidämie und Neugeborenenenzephalopathie.

OBJECTIVE: The purpose of this study was to determine the significance of fetal acidemia for newborn encephalopathy (NEP) and for the combination of NEP and multiorgan system dysfunction (MOS). In particular the influence of acidemia will be contrasted with criteria of pregnancy and delivery. STUDY DESIGN: 248 infants delivered with cord umbilical arterial pH < 7.15 (UApH) were retrospectively studied. Infants with similar or identical neonatal characteristics formed different groups: unaffected neonatal development, NEP, NEMO (NEP combined with MOS), other diseases, infection, exitus letalis. Statistics and calculations were done by means of factor analysis, univariate analysis, Student-Newman-Keuls-test, and Chi 2-test (p < 0.05). RESULTS: Twenty seven infants with UApH < 7.15 suffered from NEP. NEP in combination with MOS occurred in 11 cases. There was no relationship between the degree of acidemia and a single NEP. Infants with NEMO differ from all other groups in their mean UApH (p < 0.05). The Apgar scores 1 min and 5 min (A1, A5) separated newborns with unaffected neonatal development from all other groups (p < 0.05). UApH-differences in the group: NEMO resulted from a combination of acute intranatal fetal distress and operative delivery and a combination of A1, A5, preterm delivery, and pathologic CTG (p < 0.01). CONCLUSIONS: The degree of acidemia impacts the occurrence of NEMO. However, UApH alone does not predict this combination of characteristics. The Apgar score should be taken into account to evaluate an acidemic UApH. In case of acidemia complex factors of pregnancy and delivery are associated with an increased risk of NEMO.

Comparison of tissue polypeptide antigen (TPA) with cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) in follow-up of breast cancer.

Cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were measured in 679 sera of breast cancer patients and in 94 sera of women without breast cancer. The tumour markers were determined using immunoluminometric assays (ILMA). The assays are characterised by an inter-assay-imprecision and intra-assay-imprecision <4 %. The breast cancer patients were staged according to the TNM classification stage 0-IV (by UICC) in patient groups with a compatible prognosis. Median and range of each stage were investigated. The cut-off values (95th and 97.5th percentile of control group) of CA 15-3, CEA and TPA were determined; specificity, sensitivity, positive and negative predictive value (PV) and efficiency were investigated for these cut-off's and the receiver operating characteristic (ROC) curves were calculated. The differences between control group and stage 0-3 were shown as non-significant for CA 15-3 and CEA but significant for TPA. Significant differences were found in stage 4 for all three tumour markers. The three tumour markers did not have differences in specificity, positive and negative PV and efficiency. TPA and CA 15-3 demonstrated comparable results in sensitivity and ROC curve analyses. These results were better than those from CEA.

-Case report of clinical and pathophysiological similarities of Moschkowitz disease and HELLP syndrome-. / Kasuistik zu klinischen und pathophysiologischen Gemeinsamkeiten von Morbus Moschcowitz und HELLP-Syndrom.

This case report describes for the first time a manifestation of thrombotic thrombocytopenic purpura (TTP, Moschcowitz's disease) during pregnancy. The characteristic neurologic symptoms of TTP were missing, while the typical clinical signs of the HELLP syndrome could be observed. Furthermore the biochemical proof of TTP was obtained by tracing ultra-large clotting factor VIII (von Willebrand factor) multimers in the patient's plasma. Thus the assumption is supported that TTP and HELLP syndrome are diseases of one pathophysiological entity with different symptomatologies. Because of the frequent relapse of TTP, differentiation between TTP and HELLP syndrome is of great clinical importance, independent of future pregnancies.

[Administration of pethidine in labor with meconium contaminated amniotic fluid: effect on fetal outcome and respiratory disorders]. / Pethidin-Anwendung bei Geburten mit mekoniumhaltigem Fruchtwasser: Einfluss auf fetal outcome und respiratorische Störungen.

OBJECTIVE: The aim of the study was to evaluate the effects of maternal pethidine administration on fetal outcome and incidence of neonatal respiratory distress in deliveries with meconium stained amniotic fluid (MAF). STUDY DESIGN: Between 1989 and 1992, 849 live infants had MAF. For pain relief during labor 214 women received pethidine 50-150 mg i.m. The control group included 401 infants with MAF, who were not exposed to sedatives, analgesics, and anesthetics during labor. Fetal cord pH, Apgar 1 min (A1), Apgar 5 min (A5), and incidence of respiratory distress were compared retrospectively between the groups. Statistics and calculations were done by means of uni- and multivariate analyses. RESULTS: The presence of thickened MAF increased significantly the risk of low A1, low A5, low arterial cord pH, and the incidence of respiratory distress (p = 0.003, = 0.0003, = 0.016, = 0.000). Infants with thickened MAF, low A1, and low fetal cord pH proved to have an exceedingly high risk of respiratory distress. The application of pethidine (0 mg, 50 mg, 100-150 mg) does not discriminate the variables as arterial cord pH, A1, A5, and the incidence of respiratory distress significantly. However the medium cord pH values of infants without pethidine (7.27, s = 0.075) and with 100-150 mg pethidine (7.25, s = 0.078) were significantly different (p = 0.0006). The incidence of arterial pH, 7.10 did not differ significantly in cases with different pethidine doses. CONCLUSIONS: Thickened MAF is an obstetric hazard with small but significantly increased risks for poor fetal outcome and neonatal respiratory distress. This study failed to identify additional neonatal risks engendered by use of pethidine in cases of MAF.