Towards a better consideration of endocrine disruption within the technical guidance for deriving environmental quality standards.

Endocrine-disrupting chemicals (EDCs) are a reason for growing concern because of their substantial and long-lasting deleterious effects on human health and wildlife populations. These include direct effects on aquatic organisms and may be a concern to species feeding on the aquatic food chains and water, including humans. In the European Community, the dedicated legislative tools to protect the aquatic environment and human health from contaminants released to surface waters is the Water Framework Directive (WFD). The achievement of protection goals is assessed through the comparison of concentrations measured in the media and thresholds of no effect called Environmental Quality Standards (EQSs). As EDCs are explicitly mentioned in the WFD, an analysis of the state of the art was undertaken on how far and how consistently ED properties were considered in the derivation of EQS values. Our results reveal substantial heterogeneity according to substance and that among substances with ED evidences, EQSs have been derived without considering ED properties for 70% of them. A methodology to better consider endocrine disrupting properties is proposed and includes a logical and systematic approach to derive EQSs with a proposal to specify additional assessment factors based on the specific hazard and potential uncertainty.

New amidinate complexes of indium(iii): promising CVD precursors for transparent and conductive In2O3 thin films.

For the first time, synthesis of two new amidinate-ligand comprising heteroleptic indium complexes, namely [InCl(amd)2] (1) and [InMe(amd)2] (2), via salt-metathesis and their detailed characterization is reported. For comparison, the earlier reported homoleptic tris-amidinate [In(amd)3] (3) was also synthesized and analyzed in detail especially with respect to the thermal properties and molecular crystal structure analysis which are reported here for the first time. From nuclear magnetic resonance spectroscopy (NMR) and single-crystal X-ray diffraction (XRD), all three compounds were found to be monomeric with C2 (compound 1 and 2) and C3 symmetry (compound 3). Both halide-free compounds 2 and 3 were evaluated regarding their thermal properties using temperature-dependent 1H-NMR, thermogravimetric analysis (TGA) and iso-TGA, revealing suitable volatility and thermal stability for their application as potential precursors for chemical vapor phase thin film deposition methods. Indeed, metalorganic chemical vapor deposition (MOCVD) experiments over a broad temperature range (400 °C-700 °C) revealed the suitability of these two compounds to fabricate In2O3 thin films in the presence of oxygen on Si, thermally grown SiO2 and fused silica substrates. The as-deposited thin films were characterized in terms of their crystallinity via X-ray diffraction (XRD), morphology by scanning electron microscopy (SEM) and composition through complementary techniques such as Rutherford-backscattering spectrometry (RBS) in combination with nuclear reaction analysis (NRA) and X-ray photoelectron spectroscopy (XPS). From UV/Vis spectroscopy, the deposited In2O3 thin films on fused silica substrates were found to be highly transparent (T > 95% at 560 nm, compound 3). In addition, Hall measurements revealed high charge carrier densities of 1.8 × 1020 cm-3 (2) and 6.5 × 1019 cm-3 (3) with a Hall-mobility of 48 cm2 V-1 s-1 (2) and 74 cm2 V-1 s-1 (3) for the respective thin films, rendering the obtained thin films applicable as a transparent conducting oxide that could be suitable for optoelectronic applications.

[Bone void fillers in osteotomies : If, when, and which type?] / Füllung des Osteotomiespalts : Ob, wann und womit?

Medial opening wedge high tibial osteotomy (HTO) is an established procedure for treating medial osteoarthritis of the knee. In order to achieve the desired amount of correction, the osteotomy gap is opened, which creates a bone void in the medial aspect of the proximal tibia. The resulting bone void can either be left alone or be addressed by interposing a variety of different bone void fillers. Autologous and allogenic fillers can be distinguished from synthetic materials. Up to now, few studies have dealt with the usefulness and necessity for bone void fillers in HTO. The following article provides an overview on the currently used bone void fillers, their specific advantages and disadvantages and their influence on clinical and radiographic outcome after HTO.

[Nora's Lesion: A Rare Differential Diagnosis for Benign Peripheral Bone Tumours]. / Die Nora-Läsion: Eine seltene Differenzialdiagnose bei benignen peripheren Knochentumoren.

We report on a bizarre parosteal osteochondromatous proliferation (BPOP), also known as Nora's lesion, in a 43-year-old female patient.

Brain activation during fear conditioning in humans depends on genetic variations related to functioning of the hypothalamic-pituitary-adrenal axis: first evidence from two independent subsamples.

BACKGROUND: Enhanced acquisition and delayed extinction of fear conditioning are viewed as major determinants of anxiety disorders, which are often characterized by a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. METHOD: In this study we employed cued fear conditioning in two independent samples of healthy subjects (sample 1: n=60, sample 2: n=52). Two graphical shapes served as conditioned stimuli and painful electrical stimulation as the unconditioned stimulus. In addition, guided by findings from published animal studies on HPA axis-related genes in fear conditioning, we examined variants of the glucocorticoid receptor and corticotropin-releasing hormone receptor 1 genes. RESULTS: Variation in these genes showed enhanced amygdala activation during the acquisition and reduced prefrontal activation during the extinction of fear as well as altered amygdala-prefrontal connectivity. CONCLUSIONS: This is the first demonstration of the involvement of genes related to the HPA axis in human fear conditioning.

Silent echo-planar imaging for auditory FMRI.

INTRODUCTION: The effect of the acoustic scanner noise produced by gradient coil switching on the auditory evoked BOLD signal represents a well-known problem in auditory functional MRI (FMRI). In this paper, a new low-noise echo-planar imaging (EPI) sequence is presented that is optimized for auditory FMRI measurements. METHODS: The sequence produces a narrow-band acoustic frequency spectrum by using a sinusoidal readout echo train and a constant phase encoding gradient. This narrow band is adapted to the frequency response function of the MR scanner by varying the switching frequency of the sinusoidal readout gradient. RESULTS: Compared to a manufacturer-provided standard EPI sequence, the acoustic noise reduction amounts to up to 20 dBA. Using a simple block design paradigm contrasting presentation of a pure tone during ON blocks and "silence" (absence of the tone) during OFF blocks, the new low-noise sequence was evaluated and compared to the standard EPI sequence. Statistical parametric mapping (SPM) resulted in higher levels of significance of auditory activation for the low-noise sequence. DISCUSSION: These findings strongly suggest that the low-noise sequence may generate enhanced BOLD contrasts compared to the standard EPI sequences commonly used in FMRI.

Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors.

OBJECTIVE: To assess the value of spectroscopic and perfusion MRI for glioma grading and for distinguishing glioblastomas from metastases and from CNS lymphomas. METHODS: The authors examined 79 consecutive patients with first detection of a brain neoplasm on nonenhanced CT scans and no therapy prior to evaluation. Spectroscopic MRI; arterial spin-labeling MRI for measuring cerebral blood flow (CBF); first-pass dynamic, susceptibility-weighted, contrast-enhanced MRI for measuring cerebral blood volume; and T1-weighted dynamic contrast-enhanced MRI were performed. Receiver operating characteristic analysis was performed, and optimum thresholds for tumor classification and glioma grading were determined. RESULTS: Perfusion MRI had a higher diagnostic performance than spectroscopic MRI. Because of a significantly higher tumor blood flow in glioblastomas compared with CNS lymphomas, a threshold value of 1.2 for CBF provided sensitivity of 97%, specificity of 80%, positive predictive value (PPV) of 94%, and negative predictive value (NPV) of 89%. Because CBF was significantly higher in peritumoral nonenhancing T2-hyperintense regions of glioblastomas compared with metastases, a threshold value of 0.5 for CBF provided sensitivity, specificity, PPV, and NPV of 100%, 71%, 94%, and 100%. Glioblastomas had the highest tumor blood flow values among all other glioma grades. For discrimination of glioblastomas from grade 3 gliomas, sensitivity was 97%, specificity was 50%, PPV was 84%, and NPV was 86% (CBF threshold value of 1.4), and for discrimination of glioblastomas from grade 2 gliomas, sensitivity was 94%, specificity was 78%, PPV was 94%, and NPV was 78% (CBF threshold value of 1.6). CONCLUSION: Perfusion MRI is predictive in distinguishing glioblastomas from metastases, CNS lymphomas and other gliomas vs MRI and magnetic resonance spectroscopy.

[First experience with a critical incident reporting system in surgery]. / Critical incident reporting system. Erste Erfahrungen in der Chirurgie.

Systems that record critical incidents were initially developed for aeronautics and are being increasingly applied in medicine. The objective is to detect problems inherent to systems and system errors before they lead to complications or do harm to patients. We report our preliminary experience with a critical incident reporting system (CIRS). Since February 1 2001, all employees of our surgical department have been able to report incidents, anonymously or candidly, to a central board using a standardized documentation form. The results are presented at monthly internal quality meetings, where two to three crucial incidences are thoroughly discussed. New information is communicated and put into practice as quickly as possible. A total of 424 incidents were reported from February 1, 2001 to December 31, 2003. Reversible damages, some of which resulted in prolonged hospitalization, were consequential to 22% of the cases. Thirteen percent were classified as "near miss" (almost incidents), whereas 65% had no consequences for patients. As expected, doctors and nurses were most frequently involved, as 36% of the reported incidents occurred in connection with the prescription and administration of medication. In particular, the near miss category revealed system errors which in 85% of cases had immediate consequences for therapeutic procedures. Based on our initial experiences, working with CIRS may be evaluated as positive. The open discussion of incidents and errors also revealed minor but often significant system errors, which resulted in alteration of our internal proceedings and thus improved the quality and safety of treatment.

[Noninvasive measurement of relative cerebral blood flow with the blood bolus MRI arterial spin labeling: basic physics and clinical applications]. / Nichtinvasive Messung des relativen zerebralen Blutflusses mit der MR-Blutbolusmarkierungstechnik (arterial-spin-labeling): Physikalische Grundlagen und klinische Anwendungen.

Knowledge of tumor blood flow is important for diagnosis and follow-up of brain tumors after therapy, especially to discriminate necrosis from tumor recurrence after radiation or chemotherapy. Meanwhile, perfusion and diffusion MRI, besides MR-angiography, are state of the art in stroke imaging. Until now, perfusion imaging was mostly performed using the first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) MRI. The MRI-based arterial spin labeling technique (ASL) is a novel approach for measuring relative cerebral blood flow (rCBF) without using extrinsic contrast agents, by labeling spins of flowing arterial blood as intrinsic contrast agent. This article describes physical basics of ASL and shows clinical examples in neuroimaging such as in meningeoma, glioblastoma, oligodendroglioma, and cerebral ischemia, using the Q2TIPS ASL technique. Gray matter is clearly visible, while the observed white matter signal obtained by Q2TIPS is only slightly higher than background noise. Venous blood causes artefacts in the sagittal sinus and other large superficial veins in the subarachnoid space. Meningeoma and glioblastoma show elevated rCBF, whereas oligodendroglioma and cerebral ischemia have reduced rCBF values. Arterial-spin-labeling techniques are noninvasive tools for measuring rCBF within 5 min, using a standard MRI scanner.

[Kirschner wire transfixation of syndesmosis rupture--an alternative treatment of type B and C malleolar fractures]. / Die Kirschnerdraht-Transfixation der Syndesmosenruptur--Eine alternative Behandlung von Malleolarfrakturen Typ B und C.

After completing ORIF of the lateral malleolus, the standard technique for fixation of the syndesmosis involves placement of a 3.5 mm locking screw across the fibula to the tibia. Alternative there is a possibility to make the transfixation with two 1.6 mm Kirschner wires introduced obliquely across the distal tibiofibular syndesmosis. No early removing of the implant is necessary. This retrospective study was conducted on a total of 50 cases of Weber type B or C malleolar fractures with syndesmotic rupture between 1988 and 1996. In 45 patients (90%) there is no complication seen for the transfixation, but in five patients a Kirschner wire dislocation was observed. We were able to review 36 of these patients after a median follow-up of 8.3 years (range 5-12 years). The results were evaluated using objective, subjective and roentgenographic criteria. Subjective rating had 29 patients (81%) with very good or good results. Good radiological results were found in 29 patients (81%). Concluding of this results the Kirschner wires transfixation is a technical simple method with good or very good results.

Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration. INTERVENTION: After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds' duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance. MAIN OUTCOME MEASURES: In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone. RESULTS: Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination. CONCLUSIONS: Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.

Transpupillary thermotherapy.

Hyperthermia has long been recognized as potentially useful in the treatment of human neoplasms. Only recently has technology allowed hyperthermic treatment to be delivered to ocular structures in the form of ultrasound, microwave, or ferromagnetic energy. A novel technique, transpupillary thermotherapy, allows the direct application of hyperthermic energy to posterior segment ocular structures. The treatment of two posterior segment diseases, choroidal melanoma and choroidal neovascularization attributable to age related macular degeneration, are reviewed in this article.

c-Myb trans-activates the human DNA topoisomerase IIalpha gene promoter.

DNA topoisomerase IIalpha (topo IIalpha) is an essential proliferation-dependent nuclear enzyme which has been exploited as an anti-tumor drug target. Since the proliferative status of human leukemia cells is associated with expression of the c-myb proto-oncogene, c-Myb was investigated as a trans-activator of the topo IIalpha gene. Using topo IIalpha promoter-luciferase reporter plasmids, c-myb expression caused trans-activation of the topo IIalpha promoter a maximum of approximately 4.5-fold over basal levels in HL-60 human promyelocytic leukemia cells. Trans-activation was submaximal with higher levels of c-myb expression plasmid but a Myb protein lacking its negative regulatory domain resulted in approximately 19-fold trans-activation. Mutagenesis and 5'-deletion studies revealed that Myb trans-activation was mediated via a Myb-binding site at positions -16 to -11 and that this region governed the bulk of basal topo IIalpha promoter activity in human leukemia cells. Trans-activation of topo IIalpha by c-Myb was lymphoid- or myeloid-dependent. However, B-Myb, a more widely-expressed Myb family member, caused topo IIalpha trans-activation in both HL-60 cells and HeLa epithelial cervical carcinoma cells. These data provide evidence for a new Myb-responsive gene which is directly linked to and required for cellular proliferation.

Ultrastructural changes of Trichomonas vaginalis prior and after cryopreservation.

Fine structural changes of Trichomonas vaginalis are described prior and after the freezing process in liquid nitrogen. Dimethyl sulfoxide (DMSO) used as the cryoprotectant caused distinct alterations of the cytoplasm when trichomonads were equilibrated with 5% DMSO under various experimental conditions. Changes were bubble-like protrusions, fissuration and/or vacuolation of the cytoplasm, doubling and removal or/and rupture of the cell membrane. Apart from these findings cryopreservation caused marked alterations on the hydrogenosomes, such as condensation and flocculence of the usually homogeneous contents; in addition numerous hydrogenosomes fused while loosing membrane at the site of fusion. However, several parasites revealed normal hydrogenosomes after the freezing process. It is assumed that these organisms survived freezing and thawing as demonstrated by successful cultivation of recovered trichomonads.

Small cytoplasmic RNAs from rat liver mRNP particles. Studies on their structure and function.

Free cytoplasmic 40S mRNP particles from rat liver were treated with EDTA and separated into two populations of RNP particles with sedimentation maxima of 20S and 35S, respectively. A characteristic set of distinct scRNAs is found for 20S and 35S RNP particles. The sequences of two of the most abundant scRNAs from 20S RNP particles with chain lengths of 104 (alpha 1-RNA) and 124 (beta 1-RNA) nucleotides, respectively, are presented. alpha 1-RNA shows a high sequence homology to the 3'-end of 18S rRNA. Since alpha 1-RNA carries a cap, it cannot be a degradation product of 18S rRNA. The beta 1-RNA is strongly post-transcriptionally modified, but uncapped. When the individual scRNAs of 20S and 35S RNP particles isolated from preparative polyacrylamide gels were assayed for their capability to inhibit in vitro protein synthesis, several potent translational inhibitory RNAs were detected. Particularly, the scRNAs of 147,203 and 263 nucleotide length associated with the 35S RNP particles turned out to be strong inhibitors of protein synthesis.

Vitreous hemorrhage complicating retinal astrocytic hamartoma.

Tuberous sclerosis classically presents a triad of mental deficiency, seizures and adenoma sebaceum. Among the ocular manifestations are astrocytic hamartomas in the retina. This paper describes the case of a 24-year-old man with tuberous sclerosis who had recurrent vitreous hemorrhage from a large epipapillary astrocytic hamartoma in the left eye. Pars plana vitrectomy cleared the vitreous and bimanual bipolar coagulation of tumor bleeding points was done. Fragments of the friable tumor were obtained with the vitrectomy instrument and were prepared for tissue culture, histology, and electron microscopy. Although pars plana vitrectomy offers certain advantages over other methods of biopsy, it does present a danger of extraocular seeding of malignant cells; therefore, it is not recommended in cases with probable intraocular malignancy.