Persistent Detwinning of Iron-Pnictide EuFe_{2}As_{2} Crystals by Small External Magnetic Fields.

Our comprehensive study on EuFe_{2}As_{2} reveals a dramatic reduction of magnetic detwinning fields compared to other AFe_{2}As_{2} (A=Ba, Sr, Ca) iron pnictides by indirect magnetoelastic coupling of the Eu^{2+} ions. We find that only ∼0.1 T are sufficient for persistent detwinning below the local Eu^{2+} ordering; above T_{Eu}=19 K, higher fields are necessary. Even after the field is switched off, a significant imbalance of twin domains remains constant up to the structural and electronic phase transition (190 K). This persistent detwinning provides the unique possibility to study the low temperature electronic in-plane anisotropy of iron pnictides without applying any symmetry-breaking external force.

EuFe2(As(1-x)P(x))2: reentrant spin glass and superconductivity.

By systematic investigations of the magnetic, transport, and thermodynamic properties of single crystals of EuFe(2)(As(1-x)P(x))(2) (0≤x≤1), we explore the complex interplay of superconductivity and Eu(2+) magnetism. Below 30 K, two magnetic transitions are observed for all P substituted crystals, suggesting a revision of the phase diagram. In addition to the canted A-type antiferromagnetic order of Eu(2+) at ∼20 K, a spin glass transition is discovered at lower temperatures. Most remarkably, the reentrant spin glass state of EuFe(2)(As(1-x)P(x))(2) coexists with superconductivity around x≈0.2.

Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments.

BACKGROUND: Irreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time. MATERIAL AND FINDINGS: The patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8-16.93) for Gleason 6, 14.6% (CI95: 8.8-23.7) for Gleason 7 and 39.5% (CI95: 23.5-61.4) for Gleason 8-10. CONCLUSION: The results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore.

Comparative assessment of the functional p53 status in glioma cells.

BACKGROUND: p53 is the most frequently mutated gene in human cancers and its functional integrity is an important predictor of treatment response and clinical outcome. The majority of mutations found in different types of cancer cluster within the DNA binding domain encoded by exons 5-8. In clinical specimens the functional status of p53 is, therefore, often evaluated by direct mutation analysis of exons 5-8 or indirectly by immunostaining and evaluation of the subcellular localization pattern or protein accumulation. MATERIALS AND METHODS: In a panel of glioma cell lines, the status of the P53 gene was analyzed by temperature gradient gel electrophoresis (TGGE) of exons 5-8 and direct sequencing of all p53 exons. The nuclear accumulation of p53 in unstressed cells was assessed by immunostaining. These data were correlated with stress induction of the p53 protein, nuclear translocation and a direct determination of the transcriptional activity of endogenous p53 protein and induction of p53 target genes. RESULTS: Our analysis demonstrated that a p53 gene mutation analysis limited to exons 5-8 and analysis of immunostaining patterns can not serve as reliable predictors of functional p53 in tumor cells. Conversely, in some presumably rare cases, the transcriptional activity of p53 may be retained in tumor cells in the presence of a mutation and a pathological immunostaining pattern. In our analysis, the constitutive dephosphorylation at Ser 376 correlated with the nuclear accumulation of p53, but not with the transcriptional activity of the protein. This suggests that constitutive dephosphorylation at Ser376 may be one of the factors determining stabilization of mutant and wild-type p53, which is frequently observed in glial tumors. CONCLUSION: The incidence of a dysfunctional p53 protein in gliomas may be higher than expected, based on a single parameter evaluation by mutation analysis of exons 5-8 or assessment of p53 accumulation and subcellular localization by immunostaining.

Thromboxane synthase regulates the migratory phenotype of human glioma cells.

The capacity of glial tumor cells to migrate and diffusely infiltrate normal brain compromises surgical eradication of the disease. Identification of genes associated with invasion may offer novel strategies for anti-invasive therapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, has been identified by differential mRNA display as being overexpressed in a glioma cell line selected for migration. In this study TXsyn mRNA expression was found in a large panel of glioma cell lines but not in a strain of human astrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glial tumors and in reactive astrocytes, whereas it could not be detected in quiescent astrocytes and oligodendroglia of normal brain. Glioma cell lines showed a wide range of thromboxane B2 formation, the relative expression of which correlated with migration rates of these cells. Migration was effectively blocked by specific inhibitors of TXsyn, such as furegrelate and dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were less effective. Treatment with specific inhibitors also resulted in a decrease of intercellular adhesion in glioma cells. These data indicate that TXsyn plays a crucial role in the signal transduction of migration in glial tumors and may offer a novel strategy for anti-invasive therapies.

Effect of EDTA and citrate on the functional activity of the first component of complement, C1, and the C1q subcomponent.

The first component of complement, C1, is a calcium-dependent complex of the three distinct subcomponents, C1q, C1r, and C1s. Earlier observations revealed that treatment of C1 with EDTA led to a loss of hemolytic C1 activity even after recalcification. Therefore, it was of interest to study whether EDTA has an additional effect on C1 and its subcomponents, beside its chelating capacity. The chelating effect of EDTA was compared to that of citrate. It was found that treatment of C1 or C1 with EDTA followed by addition of Ca++ led to a loss of hemolytic activity up to 90%, depending on EDTA concentration. Even pretreatment of EDTA with varying amounts of Ca++ did not prevent the inactivation of C1 or C1. In contrast, after dissociation of C1 or C1 by citrate, 100% of the original C1q activity is recoverable on addition of C1q deficient serum as source of C1r and C1s. EDTA-treated serum, however, showed a concentration-dependent loss of hemolytic C1q activity, indicating an inhibitory effect of EDTA on C1q. EDTA-treated C1q, fluid phase or bound to EA, was no longer able to form an hemolytically active C1 complex by interaction with C1r and C1s.

Dissecting glioma invasion: interrelation of adhesion, migration and intercellular contacts determine the invasive phenotype.

The invasive cellular behavior of malignant gliomas is determined by receptor mediated cell-substratum contacts and cell-cell interaction as well as cellular locomotion. This study attempts to break down the complex phenomena of the invasive process into their components of attachment to neighboring cells, aggregate formation, adhesion to matrix substratum, migration and invasion into three-dimensional cellular aggregates separately analyzed in different in vitro assay systems. Using a panel of 13 glioma cell lines, adhesion to non-specifically or merosin coated surfaces was correlated to monolayer cell migration and dissemination of tumor cells from aggregates plated on these substrates. The formation kinetics of aggregates were determined and compared to the ability of these cells to rapidly attach and form mechanically stable cell-cell contacts. The motility rates in the different assay systems as well as cell-cell attachment was correlated to invasion of re-aggregated tumor cells into fetal rat brain. A tight positive correlation was found for substrate adhesion and monolayer migration. In contrast, cell-substratum contacts had little influence on dissemination of cells out of three-dimensional aggregates and no association between monolayer migration and migration of cells out of aggregates was detected. The ability of glioma cells to rapidly form aggregates was associated with enhanced migration out of aggregates. The capacity to invade fetal rat brain aggregates was correlated with the capacity to form stable intercellular adhesion as measured in a cell-cell adhesion assay. Invasion in this system was not found to be associated with migration in monolayer or with migration out of tumor aggregates. This study highlights that current in vitro assays for invasion only represent isolated aspects of the multi-cascade process which is involved in tumor cell invasion.

Towards in-vitro prediction of an in-vivo cytostatic response of human tumor cells with a fast chemosensitivity assay.

The objective of this study is to evaluate a novel approach to chemosensitivity testing with respect to its predictive value in the selection of clinically effective cytostatic drugs to optimize the therapeutic treatment of cancer. The chemosensitivity assay, which we used in this study, has its roots in pharmaceutical drug screening and the surrounding intellectual property is protected by various patent applications and trademarks. Therefore, we will refer to this test in the following pages as ChemoSelect. ChemoSelect is a sensor-chip based diagnostic test, which permits the functional and continuous real-time measurement of induced tumor cell cytotoxicity following the administration of chemotherapeutic drugs. Chemosensitivity is measured through the reduction of the excretion of lactic and carbonic acids--by-products of the metabolic processes of glycolysis and respiration and a parameter for cell vitality--generated specifically by ATP hydrolysis and lactic acid production. We used this test to study the applicability of this assay for tumor cells based on the analysis of tumor cell lines and tumor specimens. In this preliminary study, this test was studied in predicting chemoresistance and chemosensitivity in cell lines and tumor specimens for which the result was already predetermined by the properties of the cell line or the tumor specimen used in the experiment. The applicability in a clinical setting was studied by confirming the trends on selected drug sensitivity and drug resistance with an interim analysis of an ongoing clinical study in selected patients with breast cancer undergoing neoadjuvant chemotherapy. The minimum detection limit of cells and biologic cell responses, an important variable determining the applicability of the test in routine clinical use, was also assessed. ChemoSelect avoids many of the limitations of existing chemoresistance assays and provides more comprehensive information and output, as it has a 24-h turnaround time, is applicable to the majority of solid tumors and available cytostatic drugs, does not need more than 10(5) cells in total, cultivated tumor cells, provides dynamic monitoring of cellular responses through on-line data read-out during the perfusion with drugs and can be extended to the analysis of novel therapeutic modalities such as biologics.

Glioma cell adhesion and migration on human brain sections.

Within the brain, dissemination of glioma cells follows myelinated fiber tracts and extracellular matrix containing structures such as the basement membranes of blood vessels. These patterns represent the two major routes of invasion frequently observed in clinical disease. Previously, we have characterized the substrates for preferential glioma adhesion and migration on purified ECM protein. In this study sections of human brain from different anatomical regions were used as adhesive substrates and also characterized for the presence and distribution of matrix proteins. Adhesion of marker gene transfected glioma cell suspensions to different regions and anatomical structures of human brain was quantified using a computer assisted image analysis system. Monoclonal antibodies against different adhesion molecules were used to inhibit glioma cell attachment ot specific anatomical structures. In addition, glioma cell aggregates were allowed to adhere to brain sections and single cells were observed to migrate out of these aggregates. Scanning electron microscopy was used to morphologically study the preferred routes of glioma dissemination on brain sections. In brain sections different kinetics of cell adhesion to distinct structures were observed. Within 15 minutes cells adhered and spread on blood vessels and arachnoid tissue containing sections. Choroid plexus and the ventricular wall were also adhesive structures. Adhesion to cortex required 1 hour, while adhesion and spreading on myelinated fiber tracts was retarded and required several hours of incubation. The predominant matrix proteins in small vessels were found to be laminin, collagen type IV, and fibronectin. Choroid plexus and the ependyma showed a similar composition of matrix proteins. Arachnoid fibers contained different types of collagens, predominately type I and III, whereas the only matrix protein identified in the subependyma was fibronectin. Antibodies to the alpha 2, alpha 3, and beta 1 integrin subunits completely blocked adhesion to arachnoid tissue, anti-NCAM inhibited attachment to cortex. Adhesion to blood vessels in brain sections could only be inhibited to 50% by anti-integrin beta 1. Antibodies to the av containing integrin av beta 3 also blocked 50% of adhesion to vessels. Our findings indicate that adhesion of glioma cells to brain sections most rapidly takes place on ECM protein containing regions, especially blood vessels which may serve as guiding structures for glioma dissemination.

Darlucins A and B, new isocyanide antibiotics from Sphaerellopsis filum (Darluca filum).

Two new xanthocillin type antibiotics, darlucin A (1) and B (2), were isolated from fermentations of Sphaerellopsis filum (Darluca filum). Their structures were established by spectroscopic methods. The darlucins are the first known compounds with a 1,2-diisocyanoalkene moiety. Both compounds exhibited antibacterial, antifungal and weak cytotoxic activities.

[Functional angiography of the arteries near the knee joint: consequences for stent implantation?]. / Funktionsangiographie der kniegelenknahen Arterien: Konsequenzen für die Stentimplantation?

Angiographic studies of the arteries adjoining the knee in 25 patients show extensive kinking and stenoses of the popliteal artery and less frequently of the distal femoral artery during flexion of the knee joint. This is due to the loss of elasticity with increasing age forcing the vessel into a tortuous course during shortening of the pathway of the popliteal artery with knee flexion. Independent of the principle of the different stents available they probably will not increase the contractility of the stented vessel in the longitudinal axis. It is to expect that after implantation of stents into the popliteal artery kinking will occur predominantly in the original segments of the vessel and at the transitions to the stented segments leading to intimal damage by shear forces thus propagating local progress of atherosclerosis.

[Magnetic resonance tomography in the diagnosis of cervix cancer. Computed tomographic and histological correlations]. / Magnetresonanztomographie in der Diagnostik des Kollumkarzinoms. Computertomographische und histologische Korrelation.

The value of magnetic resonance tomography in the diagnosis of carcinoma of the cervix was studied in a prospective series of 20 patients. The results were compared with those of computed tomography and with the clinical findings. The diagnosis depended on the postoperative histology. Gynaecological examination proved superior to imaging methods in determining the extent of local tumour spread. Tumour involvement of the regional lymphatic system was better demonstrated by MRT than by CT. Exact staging proved inadequate with both these methods and the new imaging methods have not produced any changes in operative planning or technique.

[The feasibility of magnetic resonance tomography in the diagnosis of non-palpable breast tumors]. / Möglichkeiten der Magnetresonanztomographie in der Diagnostik nicht palpabler Mammatumoren.

This study deals with the role of MRI in elucidating clinically silent lesions of the breast with indeterminate changes on mammography. MRI localisation of suspected lesions was possible in all cases by using double coils after contrast enhancement of the glandular tissue, independent of the findings on mammography. Inability to demonstrate micro-calcification did not prove a disadvantage. MRI cannot provide a definite tissue diagnosis, since there is overlap between the appearances of malignant and benign lesions.

[CT arthrography in the diagnosis of shoulder instability]. / Möglichkeiten der CT-Arthrographie in der Diagnostik von Schulterinstabilitäten.

In the course of a prospective study, CT arthrography was carried out on 40 patients with shoulder instability. In 35 of these patients a lesion of the capsule and labrum was demonstrated, indicating glenohumeral instability; in three patients this was shown primarily by CT arthrography. In three patients, multidirectional instability was demonstrated. In four patients there was an isolated lesion of the labrum, whereas in one patient all the findings were normal. Compared with the capsulo-labral lesions, bone changes involving the head of the humerus and the glenoid were of lesser importance, although their severity affected the choice of operative treatment in four patients. Fifteen of the 40 patients have undergone surgery so far and in all cases the findings on CT arthrography could be confirmed.

The development of an instrument to match individuals with disabilities and service animals.

PURPOSE: There has been an increase in the use of service animals assisting persons with disabilities in the past decade. However many of the service dog agencies do not utilize an assessment that is designed to match the person to the animal in the rehabilitation and psycho-social domains. The purpose of this study was to develop the Service Animal Adaptive Intervention Assessment (SAAIA) and to measure the content validity, inter-rater reliability and clinical utility of the assessment. METHOD: Two subject groups were used. Subject group one had 43 subjects who measured the content validity and clinical utility of the SAAIA Survey. Subject group two had 12 subjects who measured the inter-rater reliability by completing the SAAIA using information obtained through a video-taped client case scenario. RESULTS: Content validity results indicated a good to high percentage of agreement and a fair percentage of agreement for clinical utility. Inter-rater reliability results indicate good to high agreement on six of the eight variables of the SAAIA. However, the Kappa score indicates low inter-rater reliability. CONCLUSION: Results indicate the SAAIA has good content validity and inter-rater reliability and fair clinical utility based on percent agreement. However, further research is needed on the reliability of the SAAIA.

(+)-10 alpha-Hydroxy-4-muurolen-3-one, a new inhibitor of leukotriene biosynthesis from a Favolaschia species. Comparison with other sesquiterpenes.

A new inhibitor of leukotriene biosynthesis, (+)-10 alpha-hydroxy-4-muurolen-3-one (1), was isolated from fermentations of Favolaschia sp. 87129. Its structure was established by spectroscopic methods. The compound exhibited no antifungal or antibacterial activities. The effects of 1 on leukotriene biosynthesis were compared with (+)-T-cadinol, (-)-3-oxo-T-cadinol, and (+)-3 alpha-hydroxy-T-cadinol, three related sesquiterpenes.

[Surgical therapy of achalasia after prior pneumatic dilatation]. / Operative Therapie der Achalasie nach vorausgegangener pneumatischer Dilatation.

Of 15 patients operated on for achalasia in the Department of General and Abdominal Surgery at the University of Mainz between September 1985 and April 1990, 14 were followed-up. All the patients had received an extramucous myotomy combined with Dor's semifundoplication; in twelve, one or more preoperative balloon dilatations had been performed. The results are reported in this study. The average age of the patients was 55.3 years (18 to 76 years), and the average follow-up period 21 months (six to 53 months). No postoperative complications were seen in any of the case. All patients reported appreciable improvements in their symptoms, six being completely symptom-free. Occasional dysphagia was reported in six cases, one patient had occasional, another frequent, nocturnal heartburn, which however had already presented preoperatively. In all seven cases submitted to postoperative radiological examination, the diameter of the esophagogastric junction was increased, and the diameter of the middle-third of the esophagus decreased. No gastroesophageal reflux or signs of inflammation were seen in any of the cases. The low complication rate and the high success rate despite prior balloon dilatation or bougienage support the use of Heller's operation combined with Dor's semifundoplication for the surgical treatment of achalasia after failed balloon dilatation.

Teaching and assessment in otolaryngology and neurology: Does the timing of clinical courses matter?

Little is known about the effectiveness of clinical courses as a learning environment. To accurately assess performance in these courses, equal conditions for all candidates are required. We investigated the influence of the proximity of the course to the students test taking, the students' learning styles, and their self-motivation for learning in relation to performance success. One hundred and eleven students were randomized into eight groups, each attending a 2 week course in otolaryngology with a high proportion of patient-related teaching, and a 2 week long course in neurology with a low level of patient-related teaching. All students took multiple-choice end-of-term exams to assess their knowledge in both subjects. There was a different time interval between the course participation and the test taking for each of the groups. Performance success was correlated with the different groups, as well as with the type of learning style (LIST questionnaire) and with motivation for learning (study interest questionnaire). Explorative rank variance analysis showed a significant correlation between students' performance on the written exam and the time interval between completion of the neurology course and test-taking, with the shortest interval corresponding to highest scores (P = 0.002). There was no such effect on the success rate in otolaryngology (P = 0.28). Study motivation was not the major component for performance success, but a strong correlation between the use of strategic and deep learning styles and success in the exam was observed (R = 0.62; P < 0.001). The duration of time between a clinical course with little practical teaching and the students' taking of the exam plays a significant role on performance success; this effect does not occur in a course with a high proportion of practical patient-related teaching. More studies on clinical courses are needed to establish how students can be given adequate opportunities to develop necessary skills for patient care and for objective success on assessment. With such further information, the effectiveness of clinical courses as a learning experience might be enhanced.