Power morcellation inside a secure endobag: a pilot study.

INTRODUCTION: Unprotected power morcellation can lead to a spread of previously undiagnosed malignancy. We present a new containment bag with two closable trocar insertion sites to reduce this risk. This pilot study was designed to assess the feasibility of this device under everyday conditions. MATERIAL AND METHODS: The containment bag was used in ten laparoscopic supracervical hysterectomies. We evaluated time requirement for bag insertion into the abdominal cavity and in-bag morcellation. A 2000 ml polyurethane morcellation bag was used for all interventions. All surgeries were carried out in a three-trocar setting. RESULTS: We carried out ten supracervical hysterectomies. No intraoperative complications and no bag ruptures occurred. The meantime requirement to insert the bag and prepare the specimen for morcellation was 10.5 min (range, 7-19 min). The mean specimen weight was 191.9 g (range, 32-710 g). Mean morcellation time was 10.5 min (range, 3-28 min), mean weight of remaining tissue and fluid in the bag after morcellation was 12.1 g (range, 7-19 g). CONCLUSIONS: The presented data demonstrate that the endobag can be successfully applied in the clinical routine. Further studies are required to evaluate additional characteristics, such as individual learning curve and time requirements.

Validation of functional fetal autonomic brain age score fABAS in 5 min short recordings.

With the objective of evaluating the functional maturation age and developmental disturbances we have previously introduced the fetal autonomic brain age score (fABAS) using 30 min fetal magnetocardiographic recordings (fMCG, Jena). The score is based on heart rate pattern indices that are related to universal principles of developmental biology. The present work aims at the validation of the fABAS methodology on 5 min recordings from an independent database (fMCG, Bochum).We found high agreement of fABAS obtained from Jena normal fetuses (5 min subsets, n = 364) and Bochum recordings (n = 322, normal fetuses). fABAS of 48 recordings from fetuses with intra-uterine growth restriction (IUGR, Bochum) was reduced in most of the cases, a result consistent with IUGR fetuses from Jena previously reported. fABAS calculated from 5 min snapshots only partly covers the accuracy when compared to fABAS from 30 min recordings. More precise diagnosis requires longer recordings.fABAS obtained from fMCG recordings is a strong candidate for standardized assessment of functional maturation age and developmental disturbances. Even 5 min recordings seem to be valuable for screening for maturation problems.

Pain medication requirements after sacropexy and combination interventions.

BACKGROUND AND OBJECTIVES: Laparoscopic surgery is associated with reduced morbidity, and postoperative pain is reduced. The aim of this study was to assess postoperative pain intensity, analgesic requirements, and the influence of cofactors after laparoscopic sacral colpopexy. METHODS: The study assessed 287 patients treated with laparoscopic sacropexy for genital prolapse with a Pelvic Organ Prolapse Quantification grade>1. Patients were asked to evaluate their pain postoperatively using a 4-point verbal pain rating scale. In addition, medical records were analyzed regarding the requirement for analgesic medication. RESULTS: Patients distinguished between abdominal pain and shoulder pain after laparoscopy. Abdominal pain reached maximum severity on day 1 and showed a good response to nonsteroidal antiphlogistics, whereas shoulder pain was rarely found (6.27%). Of the patients, 38% required no pain treatment or required 1 dose at most. The need for pain medication reached its climax on day 1 and decreased during the 5 following days. Non-opioid analgesics provided a sufficient therapeutic effect. CONCLUSION: Laparoscopic sacropexy is associated with a moderate degree of postoperative pain. Non-opioid analgesics should be preferred as first-line therapy. The typical shoulder-tip pain showed only a low prevalence in our study group. From our point of view, the low rate of shoulder-tip pain corresponded with the low intra-abdominal carbon dioxide pressure.

Fetal electrocardiographic measurements in the assessment of fetal heart rate variability in the antepartum period.

This study examines signal availability in fetal electrocardiogram (FECG) beat-to-beat acquisition and the accuracy of fetal heart rate variability (HRV) analysis in the clinical setting using a commercially available FECG monitor. Signal availability was examined in 130 FECG recordings of 0.3-17.5 h duration collected in 63 fetuses (25th-42nd week of gestation) under uncontrolled conditions. Identification of R-peaks demonstrated a signal loss of 30% ± 24% with 3.6 ± 1.7 signal gaps per minute. Median duration of the gaps within a recording was 1.8 ± 0.2 s. Per hour of recording, 1.8 ± 2.1 episodes of 5 min of uninterrupted data were found. Signal availability improved with gestational age and was poorer in women with high body-mass index. Fetal HRV between weeks 36-42 was examined on the basis of 5 min RR-interval episodes obtained under controlled quiet conditions in 55 FECG compared to 46 high quality fetal magnetocardiograms. There were no differences in RR-interval duration, its standard deviation and low frequency power. However, various measures of short-term HRV were significantly higher in the FECG data: root mean square of successive differences (10.0 ± 1.8 versus 6.6 ± 3.0 ms, p < 0.001, high frequency spectral power (24 ± 12 versus 13 ± 13 ms(2), p < 0.001) and approximate entropy (0.86 ± 0.16 versus 0.73 ± 0.24, p = 0.007). We conclude that, in spite of considerable signal loss, FECG recordings can accurately estimate heart rate and its overall variance. However, measures that quantify short-term beat-to-beat HRV will be compromised due to possible recurring inappropriate detection of single R-peaks.

What is the "normal" fetal heart rate?

Aim. There is no consensus about the normal fetal heart rate. Current international guidelines recommend for the normal fetal heart rate (FHR) baseline different ranges of 110 to 150 beats per minute (bpm) or 110 to 160 bpm. We started with a precise definition of "normality" and performed a retrospective computerized analysis of electronically recorded FHR tracings. Methods. We analyzed all recorded cardiotocography tracings of singleton pregnancies in three German medical centers from 2000 to 2007 and identified 78,852 tracings of sufficient quality. For each tracing, the baseline FHR was extracted by eliminating accelerations/decelerations and averaging based on the "delayed moving windows" algorithm. After analyzing 40% of the dataset as "training set" from one hospital generating a hypothetical normal baseline range, evaluation of external validity on the other 60% of the data was performed using data from later years in the same hospital and externally using data from the two other hospitals. Results. Based on the training data set, the "best" FHR range was 115 or 120 to 160 bpm. Validation in all three data sets identified 120 to 160 bpm as the correct symmetric "normal range". FHR decreases slightly during gestation. Conclusions. Normal ranges for FHR are 120 to 160 bpm. Many international guidelines define ranges of 110 to 160 bpm which seem to be safe in daily practice. However, further studies should confirm that such asymmetric alarm limits are safe, with a particular focus on the lower bound, and should give insights about how to show and further improve the usefulness of the widely used practice of CTG monitoring.

Intrapartum signal quality with external fetal heart rate monitoring: a two way trial of external Doppler CTG ultrasound and the abdominal fetal electrocardiogram.

OBJECTIVE: The objective of this study was to assess the fetal heart rate (FHR) signal quality of non-invasive abdominal fetal electrocardiogram (fECG) in comparison to the Doppler ultrasound cardiotocogram (CTG) during the first and second stage of labour. STUDY DESIGN: This was a prospective observational study of non-invasive fECG using five abdominally sited electrodes against the traditional Doppler ultrasound CTG probe on 144 patients. Data were analysed for signal quality before and after outlier removal. RESULTS: Abdominal fECG signal quality was significantly better during the first stage of labour in comparison to Doppler CTG (median fECG reliability of 95.7 % vs. median 87.3 % for Doppler, p < 0.001), whereas during second stage of labour, equivalence was demonstrated (p > 0.05). For the first and second stage of labour, fECG showed 106/135 (78.5 %) and 46/98 (46.9 %) women having fetal signal loss below 20 %, respectively. Similarly, Doppler ultrasound demonstrated 104/135 (77.0 %) and 51/98 (52.0 %) women having fetal signal loss below 20 % during first and second stage of labour, respectively. CONCLUSION: The non-invasive abdominal fECG presents an improved FHR signal quality during the first stage of labour and an equivalent signal quality during the second stage.

The German version of the 'ICIQ Vaginal Symptoms Questionnaire' (German ICIQ-VS): an instrument validation study.

INTRODUCTION: No validated questionnaire that evaluates vaginal symptoms is currently available in the German language. Here, we report the translation and validation process of the German ICIQ-VS. SUBJECTS: Pilot study: 10 patients without any specific disease. MAIN STUDY: 58 Patients (cases) suffering from genital descensus higher than grade 1 pelvic organ prolapse quantification (POPQ) and 51 patients (controls) without vaginal affections. METHODS: To establish a cultural-adaptive equivalent in German, recommendations from Guillemin et al. [J Clin Epidemiol 1993;46:1417-1432] were carefully followed. Participants of the main study were asked to fill in the questionnaire at three time points [baseline (T1), 7 days later (T2) and 1 year later (T3)]. Reliability, validity and sensitivity to change were evaluated. RESULTS: In our pilot study, all questionnaire items were correctly interpreted and answered. In the main study, no changes from the original format were observed after translation and cultural adaptation. For the cases, internal consistency was acceptable (Cronbach's alpha 0.72-0.79) and test-retest reliability was moderate to near-perfect for single items (weighted kappa 0.67-0.94). Sensitivity to change and content validity were excellent. Construct validity revealed statistically significant differences between groups. CONCLUSION: The ICIQ-VS has successfully been translated and validated into the German language.

A prospective randomized placebo-controlled study of the effect of acupuncture in infertile patients with severe oligoasthenozoospermia.

In this first prospective, randomized, single-blind, placebo-controlled study, 28 infertile patients with severe oligoasthenozoospermia received acupuncture according to the principles of traditional Chinese medicine (TCM) and 29 infertile patients received placebo acupuncture. A significantly higher percentage of motile sperm (World Health Organization categories A-C), but no effect on sperm concentration, was found after acupuncture compared with placebo acupuncture.

Effect of prenatal antiarrhythmic treatment on cardiac function in a twin pregnancy.

We present a case of supraventricular tachycardia affecting one fetus in a twin pregnancy. Before and after treatment with flecainide and cardioversion, we examined conduction times and heart rate variability (HRV) in both twins on the basis of magnetocardiography. Cardiac conduction times increased in both fetuses but HRV showed opposing effects with a number of HRV measures. This case demonstrates that magnetocardiography not only enables identification of fetal arrhythmia, but also permits the investigation of the effects of antiarrhythmic treatment on the conductive system as well as on interaction with the autonomic nervous system.

Diagnosis, treatment, observation and outcome of fetal supraventricular tachycardia in a twin pregnancy.

BACKGROUND: Magnetocardiography and M-mode fetal echocardiography are non-invasive techniques capable of identifying fetal arrhythmias. The STAN-fetal scalp electrode system can record the fetal echocardiogram in labor. CASE: A patient was admitted to hospital with preterm contractions and cervical insufficiency at 28 weeks of gestation. After treatment with a beta-sympathomimetic drug (Partusisten) one fetus developed supraventricular tachycardia. After terminating the Partusisten medication, there was no effect on the fetal arrhythmia and flecainide therapy was initiated. Maintenance dosages controlled the condition thereafter. Cardiac time intervals of a fetus in labor can be presented, which did not change significantly throughout the first stage of labor. CONCLUSION: Flecainide is an effective therapy for supraventricular tachycardias in a twin pregnancy. Analyzing the cardiac time intervals during pregnancy can improve perinatal outcome.

The stromal cell-derived factor-1alpha dependent migration of human cord blood CD34 haematopoietic stem and progenitor cells switches from protein kinase C (PKC)-alpha dependence to PKC-alpha independence upon prolonged culture in the presence of Flt3-ligand and interleukin-6.

Addition of the inflammatory cytokine interleukin (IL)-6 to the culture medium of human cord blood haematopoietic stem and progenitor cells (HSPCs) has been shown to lead to an altered stromal cell-derived factor-1alpha-dependent migratory phenotype. This study investigated whether this effect was attributed to a differential engagement of protein kinase C (PKC) isotypes. The migratory activity of both Flt3-ligand and Flt3-ligand/IL-6 cultured cord blood HSPCs was PKC-alpha dependent on day 1, but PKC-alpha independent after 5 d of cultivation. PKC-alpha expression was not down-regulated in cells cultured for 5 d indicating a switch of signalling molecules directing cell migration.

Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner.

To date, cancer is still the second most prevalent cause of death after cardiovascular diseases in the industrialized word, whereby the primary cause of cancer is not attributed to primary tumor formation, but rather to the growth of metastases at distant organ sites. For several years it was considered that the well-known phenomenon of organ-specific spreading of tumor cells is mostly a mechanical process either directed passively due to size constraints (mechanical trapping theory) or due to a fertile environment provided by the organ in which tumor cells can proliferate (seed and soil hypothesis). Both mechanisms strongly depend on the adhesive properties of tumor cells either to endothelial cells and/or cancer cells, which are facilitated by a variety of cell adhesion molecules including carbohydrates and integrins. Within the past years it became evident that the organ-specific metastatic spreading of tumor cells does not only rely on heterotypic and homotypic adhesive interactions, but also on the interplay of chemokines and their appropriate receptors. Moreover, the identification of cancer stem cells in various tumor tissues has opened new questions. Cancer stem cells possess self-renewal, differentiation, and tumor-initiating capacities. Thus these cells are ideal candidates to be the seed of a secondary tumor. In the present review we will give a brief overview about the complex process of organ-specific metastasis formation depending on the interplay of adhesion molecules, chemokines, and the putative role of cancer stem cells in metastasis formation.

Alteration in the gene expression pattern of primary monocytes after adhesion to endothelial cells.

Monocytes originate from precursors made in the bone and remain in the circulation for nearly 24 h. Much effort has been done to identify the molecules regulating transendothelial migration of monocytes during inflammatory conditions. In contrast, considerably less is known about the process of constitutive monocyte emigration although nearly 340 million monocytes leave the circulation each day in healthy individuals. Previous studies indicated that chemokines were up-regulated in monocytes cocultured with endothelial cells that induce the retraction of the latter cell type, thereby increasing vascular permeability. Thus, we hypothesized that the utilities required for efficient constitutive monocyte extravasation are generated by monocytes themselves because of adhesion to naïve endothelial cells. To test this hypothesis, cDNA microarray analysis was performed to determine the changes in the gene expression pattern of primary monocytes that have been attached to endothelial cells compared with monocytes that were held in suspension, and we were able to identify three major groups of genes. The first group includes genes such as matrix metalloproteinase 1, monocyte chemoattractant protein 1, and tissue transglutaminase 2, which are likely required for monocyte extravasation. The second group consists of genes that are expressed in phagocytes such as caveolin-1 and CD74. Finally, the third group comprises genes that are expressed in cells of endothelial tissue and cartilage including E-selectin, fibronectin-1, matrix Gla protein, and aggrecanase-2. In summary, we conclude that adhesion of peripheral blood monocytes to naïve endothelial cells has two effects: mandatory extravasation-specific genes are regulated, and the differentiation program of monocytes is initiated.

Testing of functional integrity of p53 protein in primary breast cancer by a rapid quantitative p53-p21 double assay may improve the clinical value of p53.

We hypothesized that inclusion of p21(WAF1), an indicator of biological function, into the p53 assay might improve the clinical value of p53 in breast cancer diagnosis. In primary breast carcinomas (n = 146) and healthy/benign controls (n = 40), the p53 protein was quantified by luminescence immunoassay. The p21 protein was simultaneously measured by quantitative ELISA in a representative subgroup of breast cancers (n = 52) and controls (n = 17). In controls, p53 but not p21 was detectable. In almost all cancer tissues, p53 and p21 expression could be quantified. There was no correlation between the concentrations of both proteins. However, if p53 exceeded a threshold of 1.0 ng/mg protein, p21 expression was significantly reduced compared with samples with p53 below threshold. p21 was normally distributed in the low-p53 subpopulation, but not in the high-p53 group. The histologic parameter 'grade III' was more often found (p = 0.002) in tumors with p53 >1.0 ng/mg protein than in those with p53 below the threshold. Histological criteria of high tumor malignancy were found more often in cases with high p53 but low p21. Consequently, in clinical routine, a quantitative double assay of p53 and p21(WAF1) might help to discriminate breast cancers with preserved or impaired/lost p53 function.

Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.

OBJECTIVE: To determine the effect of luteal-phase acupuncture on the outcome of IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Randomized, prospective, controlled clinical study. SETTING: University IVF center. PATIENT(S): Two hundred twenty-five infertile patients undergoing IVF/ICSI. INTERVENTION(S): In group I, 116 patients received luteal-phase acupuncture according to the principles of traditional Chinese medicine. In group II, 109 patients received placebo acupuncture. MAIN OUTCOME MEASURE(S): Clinical and ongoing pregnancy rates. RESULT(S): In group I, the clinical pregnancy rate and ongoing pregnancy rate (33.6% and 28.4%, respectively) were significantly higher than in group II (15.6% and 13.8%). CONCLUSION(S): Luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.

Visualization of tumor cell extravasation.

In cancer the blood-borne spread of tumor cells leads to the formation of secondary tumors at distant loci, whereby the extravasation of tumor cells is a prerequisite step during hematogenous metastasis. In regard to the fate of endothelial cells located at the site of tumor cell infiltration, tumor cell-endothelial interactions were analyzed using an in vitro real-time model. This model shows the complete sequence of the transmigration process and gave new insights into the complex and dynamic cell-cell and cell-matrix interactions which occur during tumor cell transmigration across the endothelial barrier. An in vitro real-time apoptosis assay permits the distinction between apoptotic cell death from necrotic cell death. This model indicates that transmigration of tumor cell clusters derived from the invasive human bladder carcinoma cell line T24 irreversibly damages the endothelial cells by inducing apoptosis at the site of tumor cell infiltration. It is postulated here that apoptosis induction facilitates the removal of detached endothelial cells, thereby forestalling a local inflammatory response which might be detrimental to extravasating tumor cells.

Gender-related changes in magnetocardiographically determined fetal cardiac time intervals in intrauterine growth retardation.

Prenatal growth deficiencies as well as gender have been associated with cardiovascular disease in later life. It is also known that the duration of fetal cardiac time intervals (CTI) are dependent on fetal development. The aim of this work was to examine the relationship between fetal CTI in healthy and intrauterine growth retardation (IUGR) fetuses, taking gender into account. A total of 269 magnetocardiograms (MCG) were obtained in 47 healthy and 27 IUGR pregnancies. In each signal-averaged MCG, durations of CTI were determined. Age- and heart rate-corrected values were compared between normal and IUGR fetuses separately with respect to gender. Overall, there was an association between atrial and ventricular conduction times and estimated fetal body weight. In female fetuses, IUGR was associated with shorter P WAVE, PQ segment, PR interval, and QRS complex and longer STT and QT intervals. For males, this was so only for P wave, QRS complex, and STT interval. The shortening of conduction times in IUGR may be explained by reduced cardiac muscle mass associated with lower body weight. On the other hand, the gender-specific differences, particularly in the IUGR fetuses may be due to hormonal factors.

Prevention of surgery-induced suppression of granulocyte function by intravenous application of a fermented extract from Viscum album L. in breast cancer patients.

Surgical stress and anaesthetics are able to suppress the immune system. This may accelerate the growth and metastasis of residual cancer cells. As Viscum album L. extracts (VA-E) are known to exert both effects, immunomodulating and apoptosis-inducing properties, a Good-Clinical-Practice-guided, prospective bi-centric phase II study was conducted to measure the influence of a perioperative intravenous application of a VA-E on granulocyte function. In 98 patients with breast cancer, it was shown that a single intravenous application of the standardized VA-E "Iscador M special" in a final concentration of 1 mg/individual prior to surgery prevented the surgery-associated inhibition of the oxidative burst. As no VA-E-related side-effects were observed, this distinct route of application may be a rationale to restrict immunosuppression by surgical stress and anaesthesia.

Role of the beta1-integrin subunit in the adhesion, extravasation and migration of T24 human bladder carcinoma cells.

The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell-cell and cell-matrix interactions. We investigated the role of integrin subunits in the adhesion, extravasation and migration of the highly invasive human bladder carcinoma cell line T24. Here we show that inhibition of the beta(1)-integrin subunit using the specific beta(1)-integrin blocking antibody 4B4 significantly reduces the adhesion to HUVEC and transmigratory activity of T24 cells. The blockade of the beta(1)-integrin subunit also resulted in a significantly reduced locomotory activity of T24 cells. A detailed cell migration analysis on a single cell level revealed that blockade of the beta(1)-integrin subunit leads to an altered migration pattern of single cells but does not influence migration per se. Migration parameters such as time active, velocity and distance migrated were significantly reduced as compared to untreated control cells. Our observations strongly suggest a central role for the beta(1)-integrin subunit in forming the cell-cell and cell-matrix bonds necessary for adhesion, extravasation and migration.

3D-extravasation model -- selection of highly motile and metastatic cancer cells.

Extravasation has been described as a rate-limiting step in the process of hematogeneous metastasis formation. Thereby, transendothelial migration of tumor cells consists of a complex series of events involving multiple cell-cell and cell-matrix interactions. 3D-extravasation assays are valuable tools for the identification of genes, which are the key players at switchboards of the intracellular signaling pathways. In consequence, the combination of 3D-modeling and whole genome expression analysis lead to unravel molecular parameters which descripe distinct clinical phenotypes of cancer and therefore, work as prognosticators, predictors of therapy and new therapy targets.