[Ambulant Management in Case of Premature Rupture of Membranes (PROM) at Term: Maternal and Perinatal Outcome]. / Ambulantes Management bei vorzeitigem Blasensprung (VBS) am Termin. Eine Outcome-Analysestudie bei ambulantem vs. stationärem Management.

Introduction: It is estimated that after premature rupture of membranes (PROM) at term, 60% of all women go into labour within 48 h, 95% within 72 h. Often labour is induced after 24 h because the risk of maternal and neonatal infection rises. The majority of clinicians advise hospital care to allow monitoring and detection of problems. But for low-risk patients who meet strict inclusion criteria, sometimes home management is possible. This study examines the safety and costs of home management. Material and Methods: We included 239 patients with PROM at term, 202 of them with hospital and 37 with home management. Patients who met the inclusion criteria were checked 12 h after PROM and were induced by the end of 24 h if labour had not begun spontaneously. Results: There were no differences in maternal or neonatal outcome. Women with home management were likely to spend less time in hospital and this was associated with reduced costs. Conclusion: Women with outpatient management of PROM had a shorter hospitalization stay without negative impact on maternal or fetal outcome. In times of increasing financial pressure on the medical system, outpatient management for PROM seems to be a viable option.

Time-resolved analysis of transcriptional events during SNAI1-triggered epithelial to mesenchymal transition.

The transcription regulator SNAI1 triggers a transcriptional program leading to epithelial to mesenchymal transition (EMT), providing epithelial cells with mesenchymal features and invasive properties during embryonic development and tumor progression. To identify early transcriptional changes occurring during SNAI1-induced EMT, we performed a time-resolved genome-scale study using human breast carcinoma cells conditionally expressing SNAI1. The approach we developed for microarray data analysis, allowed identifying three distinct EMT stages and the temporal classification of genes. Importantly, we identified unexpected, biphasic expression profiles of EMT-associated genes, supporting their pivotal role during this process. Finally, we established early EMT gene networks by identifying transcription factors and their potential targets which may orchestrate early events of EMT. Collectively, our work provides a framework for the identification and future systematic analysis of novel genes which contribute to SNAI1-triggered EMT.

Retraction: miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers.

At the request of the University of Luxembourg and following an external investigation, the Editor and Publisher have agreed to retract this paper owing to unreliable data.

Endoscopic adrenalectomy for pheochromocytoma: difference between the transperitoneal and retroperitoneal approaches in terms of the operative course.

BACKGROUND: Due to the intraoperative catecholamine secretion with hemodynamic changes, a larger tumor size and marked neovascularization, as compared with other adrenal pathologies, endoscopic adrenalectomy for pheochromocytoma represents a particular challenge involving a more difficult and morbid procedure. The aim of this study was to identify the optimal surgical approach for endoscopic adrenalectomy in patients with pheochromocytoma. METHODS: Over a period of 10 years (February 1994 to June 2004), 38 consecutive patients underwent endoscopic adrenalectomy for pheochromocytoma. As three patients underwent a bilateral procedure, a total of 41 adrenalectomies were performed. The transperitoneal approach was carried out in 23 patients, whereas 18 patients underwent a retroperitoneal adrenalectomy by a single operative team. Perioperative parameters were prospectively followed. RESULTS: There was no conversion to the open procedure. Intraoperative hypertensive episodes occurred in 21 patients (55.3%) and were controlled by antihypertensive agents. In 11 patients (28.9%), blood pressure values rose to above 200 mmHg (> 1 min). A comparison between the retroperitoneal and transperitoneal procedures did not show a significant difference between the maximum intraoperative systolic (p = 0.730) and diastolic (p = 0.663) blood pressure values although intraoperative blood pressure peaks were seen more frequently during retroperitoneal adrenalectomy. The operative time was shorter for the patients who had transperitoneal adrenalectomy than compared to for those who had retroperitoneal adrenalectomy, although the difference was not significant. The intraoperative blood loss, perioperative morbidity, and length of postoperative hospital stay did not differ significantly between the surgical techniques (p > 0.05). CONCLUSION: After adequate preparation, endoscopic adrenalectomy may be performed in patients with pheochromocytoma via both the retroperitoneal and the transperitoneal approaches. The shorter operating time, less frequent intraoperative blood pressure peaks, and the better overview of the operating field recommend the transperitoneal approach with the patient placed in a lateral position as the preferred operative procedure.

Release of glutamate, nitric oxide and prostaglandin E2 and metabolic activity in the spinal cord of rats following peripheral nociceptive stimulation.

Peripheral tissue injury and inflammation may result in a facilitated spinal nociceptive transmission and central sensitization. Particularly, nitric oxide (NO) and prostaglandins (PGs) have been shown to be key mediators involved in the induction and maintenance of this state. By means of spinal cord microdialysis we have determined interstitial glutamate, NO (NO2-/NO3-), PGE2, glycerol, glucose and lactate concentrations in the dorsal horns of the spinal cord following peripheral nociceptive stimulation to gain further insight into the link between excitatory neurotransmitters and metabolic functions in the spinal cord during nociception. Formalin and zymosan injection into one hind paw evoked a biphasic release of glutamate and NO with the glutamate peaks preceding those of NO. Moreover, zymosan induced a biphasic increase of interstitial glycerol concentrations accompanied by an increase of interstitial lactate indicating metabolic disturbances. In contrast, formalin injection led to an elevation of dialysate glucose concentrations which may be interpreted as an indication of enhanced metabolic activity. The sequential release of glutamate and NO in the dorsal horns of the spinal cord in response to peripheral nociceptive stimulation supports the theory that NO may act as a retrograde transmitter. The metabolic changes observed after formalin and zymosan injection suggest that an intense peripheral nociceptive stimulation may not only activate but also disturb metabolic activity and possibly membrane integrity in the spinal cord.

Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis.

In a randomized double-blind study, 36 patients with osteoarthritis of the knee, hip, and/or spine were treated orally with a daily dose of S-adenosylmethionine (SAMe)(1,200 mg) or indomethacin (150 mg) over a period of four weeks. Pretreatment and posttreatment clinical parameters were determined and assessed according to a standard scoring system. SAMe therapy significantly improved the total score obtained by the sum of all clinical findings, as compared with pretreatment values. Similar improvement was evident in indomethacin-treated subjects. Two patients in the SAMe group reported slight nausea after two weeks of therapy, whereas adverse effects developed in seven patients in the indomethacin group.

Extracting the dynamics of perceptual switching from 'noisy' behaviour: an application of hidden Markov modelling to pecking data from pigeons.

When studying animal perception, one normally has the chance of localizing perceptual events in time, that is via behavioural responses time-locked to the stimuli. With multistable stimuli, however, perceptual changes occur despite stationary stimulation. Here, the challenge is to infer these not directly observable perceptual states indirectly from the behavioural data. This estimation is complicated by the fact that an animal's performance is contaminated by errors. We propose a two-step approach to overcome this difficulty: First, one sets up a generative, stochastic model of the behavioural time series based on the relevant parameters, including the probability of errors. Second, one performs a model-based maximum-likelihood estimation on the data in order to extract the non-observable perceptual state transitions. We illustrate this methodology for data from experiments on perception of bistable apparent motion in pigeons. The observed behavioural time series is analysed and explained by a combination of a Markovian perceptual dynamics with a renewal process that governs the motor response. We propose a hidden Markov model in which non-observable states represent both the perceptual states and the states of the renewal process of the motor dynamics, while the observable states account for overt pecking performance. Showing that this constitutes an appropriate phenomenological model of the time series of observable pecking events, we use it subsequently to obtain an estimate of the internal (and thus covert) perceptual reversals. These may directly correspond to changes in the activity of mutually inhibitory populations of motion selective neurones tuned to orthogonal directions.

Improved detection and differentiation of poleroviruses infecting beet or rape by multiplex RT-PCR.

Three distinct species of virus inducing yellowing of beet, Beet mild yellowing virus (BMYV), Brassica yellows virus (BrYV, synonym BWYV) and Beet chlorosis virus (BChV) have been characterised from the genus Polerovirus. Until recently, no available tools were available to allow accurate and reliable distinction of the three species. Based on previous nucleotide sequence alignments and phylogenetic studies, we show that the use of molecular methods enabled the discrimination of these three beet Polerovirus species, but with differences in efficiency and specificity. Primers CP+ and CP- encompassing ORF-3, which encodes the coat protein, allowed the amplification by RT-PCR of a fragment of 563 bp for all isolates. Molecular methods such as SSCP or RFLP were able to discriminate these fragments by utilizing the differences in sequence. However, SSCP is a highly sensitive technique and was not suitable for the distinction of the Polerovirus species, because all isolates tested displayed a unique pattern. Analysis of the ORF3 RT-PCR products, digested with SmaI, RsaI and AccI restriction enzymes revealed four distinct patterns specific for the three species. However, point mutations can alter the RFLP patterns, making the interpretation of the results difficult. Primers were designed to amplify specifically sequences corresponding to ORF-0 of the three viral species. By using the three new sets of ORF-0 specific primers and CP+/CP- primers in a single multiplex RT-PCR, the detection and discrimination of the three beet Polerovirus species was possible in infected plants. The multiplex RT-PCR method provides a reliable and highly sensitive method to detect and identify viral species and will be of great interest for epidemiological studies of beet poleroviruses.

Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee.

Hylan G-F 20, which is derived from hyaluronan, is a highly purified, elastoviscous fluid with rheologic properties similar to those of synovial fluid in the knee joints of healthy young persons. The efficacy and safety of viscosupplementation with hylan G-F 20 were evaluated in a multicenter, double-masked clinical study in patients with chronic idiopathic osteoarthritis (OA) of the knee of 1 to 30 years' duration. Three intra-articular injections of 2 mL hylan G-F 20 were administered 1 week apart to 57 knees. The control group (60 knees) received 2 mL of physiologic buffered saline solution at the same intervals. Patients were predominantly female (65%), with a mean age of 62 years and mean weight of 76 kg. Using a visual analogue scale, patients assessed the following clinical variables: pain during weight-bearing, pain at rest during the night, reduction of pain during the most painful movement of the knee, and treatment success. Evaluators also assessed patients' loss of activity while performing difficult daily tasks and treatment success. There was dramatic early improvement in all six variables with hylan G-F 20 beginning after the first injection; the improvement continued through the study end points. The differences between hylan G-F 20 and saline treatment were statistically significant for all outcome measures. In the hylan G-F 20 group, 39% to 56% of patients were free or nearly free of weight-bearing pain 10 to 24 weeks after the last injection. Treatment with saline was less effective, with fewer than 13% of patients free or nearly free of weight-bearing pain. Use of rescue therapy was significantly greater in the saline group than in the hylan G-F 20 group. No adverse events were observed in the injected joint after hylan G-F 20 treatment. These results demonstrate that hylan G-F 20 is effective and well tolerated in the management of chronic idiopathic OA.

The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan.

The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan.

Evidence for multistability in the visual perception of pigeons.

Perceptual multistability refers to cases where perception alternates between two or more interpretations of an unchanging sensory stimulus. In a first experiment we trained eight pigeons to discriminate horizontal and vertical apparent motion stimuli and then presented a multistable display. In five cases their behavior showed alternations similar to human experiments. In a second experiment we varied the aspect ratio of the display in order to support the hypothesis of a percept-driven nature of the switching behavior. The pecking rates and mean phase durations varied as predicted. This is the first evidence of visual multistability in animals confronted with classical ambiguous figures. The data suggest a stochastic mechanism.

Generalization and discrimination of shape orientation in the pigeon.

Pigeons learned to peck a green key on which parallelogram-shapes were projected; they then received generalization tests in which the orientation of the parallelogram was varied. Nondifferential training produced very little eventual stimulus control along the orientation dimension, but when training included S- trials (absence of the parallelogram) subjects responded consistently more to certain orientations than to others. Unlike typical results for visual generalization (e.g., line-tilt), the tilt gradients obtained for this complex stimulus were bimodal, supporting predictions on the basis of human perceptual data. However, unimodal gradients could be produced by specific discrimination training along the orientation dimension. Other forms of intradimensional training also produced relatively steep gradients, often characterized by unexpected but consistent secondary peaks. An attempt to obtain inhibitory gradients (S+: green key; S-: parallelogram on a green background) resulted in virtually zero responding all along the shape-orientation dimension; therefore, specific inhibitory control could not be evaluated. All these experiments suggest that definition of this complex stimulus dimension in terms of mere "angular orientation" is inappropriate, and alternative interpretations are discussed.

[The idiopathic pain syndrome]. / Das Idiopathische Schmerzsyndrom (I.S.S.).

Acute pain is "the barking police-dog of our health". It represents an efficient system of information introducing or evoking a series of defensive mechanisms concerning acute illness, whereas the chronic ache is senseless, because it doesn't take over any protective functions; on the contrary, it burdens the total organism, especially the vegetativum and the psyche as well. Chronic pain very often renders independent, then it is no longer any symptom of a disease, but the disease itself: the idiopathic or unspecific syndrome of pain. Analyzing, for example, rheumatological aspects of a case, you can recognise that there exist continuous transitions from concrete local pain to diffuse indefinite psychalgia, whilst that gliding scale is more and more defined by psychic causes. Many aspects of cases imply a lot of such components. Obviously those syndromes of diseases are increasing where only pure psychosomatic facts exist, that is to say when soma is not the primary source but the scenery.

[The choice between transperitoneal and retroperitoneal adrenalectomy. A prospective study]. / Transperitoneale oder retroperitoneale Adrenalektomie. Ergebnisse einer prospektiven Verlaufsbeobachtung.

INTRODUCTION: The aim of this prospective study was to evaluate the optimal surgical approach to endoscopic adrenalectomy. PATIENTS AND METHODS: Between March 1997 and February 2003, we performed 221 endoscopic adrenalectomies in 202 patients (right side 83, left side 100, bilateral 19), with an conversion rate of 2,5%. In 197 patients endoscopic adrenalectomy was carried out via retropertioneal approach 128 times and via transperitoneal approach 88 times. RESULTS: Endoscopic adrenalectomy was performed in 98% of the total number patients. No statistically significant influence ( P=0.05) was found for the parameters intraoperative blood loss, rate of postoperative complications, or duration of hospitalization in regard to the procedure. The operative time and learning curve were significantly longer with the retroperitoneal approach. Multivariate analysis identified surgical approach, tumor size (5 cm), and body mass index (25) as independent factors for operative time. CONCLUSION: The lateral transperitoneal approach is the optimal procedure for endoscopic adrenalectomy.

[The status of regional long-term chemotherapy in liver metastasis]. / Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen.

In numerous tumors, metastasis can be limited to the liver. In non-resectable patients, regional treatment modalities, especially arterial cytostatic infusion, are favored in contrast to systemic chemotherapy, whereas intraportal or intraperitoneal application is not successful. Improved results with high response rates have been reported after development of intra-arterial (i.a.) long-term regimens with FUdR in patients with colorectal liver metastases using implantable pumps and ports. However, a survival benefit could only be demonstrated in comparison with a control group only treated symptomatically. Because of several reports on major local toxicity of i.a. FUdR treatment (i.e. chemical hepatitis and biliary sclerosis) several other effective i.a. 5-FU regimens have been developed. A randomized study has demonstrated superiority of i.a. 5-FU versus i.a. FUdR. In comparison with systemic treatment, superiority has only been demonstrated in patients with an intrahepatic tumor burden of < 25%. Publications about regional treatment of patients with breast, gastric cancer or carcinoid liver metastases are rare. Despite the high response rates reported, the benefit of arterial chemotherapy remains questionable. Overall, local long-term chemotherapy cannot be recommended outside of studies as a primary treatment. However, extensive experience and new drugs support the idea of conducting further regional studies.

Aggressive Breast Cancer during Pregnancy with a Rare Form of Metastasis in the Maternal Placenta.

Breast cancer is the second most common cancer diagnosed during pregnancy. Here we describe a 29-year-old patient with a recurrence of breast cancer with simultaneous brain, pulmonary and placenta metastasis. An overview of the literature on placenta metastases is provided together with a report on the interdisciplinary medical management.

Nocturnal blood pressure but not insulin resistance influences endothelial function in treated hypertensive patients.

The impact of insulin sensitivity, casual blood pressure and 24-h ambulatory blood pressure on endothelial function was studied in treated hypertensive subjects. Flow-mediated dilatation of the brachial artery after reperfusion was used to determine endothelial function. Insulin sensitivity indices were obtained by using the homeostasis model assessment, after 75 g Dextrose oral glucose tolerance tests (Matsuda index) and the euglycemic hyperinsulinemic clamp (M-value) in 49 patients with arterial hypertension. The insulin sensitivity indices were compared with healthy controls matched for body weight, age and sex (n=23). Hypertensive patients under therapy were insulin resistant, had higher LDL-cholesterol levels, higher blood pressure and lower endothelial function than healthy controls. Flow-mediated dilatation showed, in the study population being treated for arterial hypertension, no relationships of all insulin sensitivity indices with flow-mediated dilatation, casual blood pressure in the morning before the tests and 24-h ambulatory blood pressure. Flow-mediated dilatation was strongly influenced by nocturnal systolic and diastolic 24-h ambulatory blood pressure (systolic: R²=0.0943, P<0.05; diastolic: R²=0.0947, P<0.05). Therefore, endothelial function in these patients is predominantly influenced by nocturnal systolic and diastolic blood pressure and not by insulin sensitivity.

miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers.

Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3'-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.