Pediatric postmortem CT angiography: validation of vascular access for PMCT angiography in stillbirths, babies and toddlers.

PURPOSE: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA). MATERIALS AND METHODS: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging. RESULTS: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice. CONCLUSION: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used.

[Medicolegal aspects of child abuse]. / Rechtsmedizinische Aspekte der Kindesmisshandlung.

CLINICAL ISSUE: The prevention and clinical diagnostics of maltreatment of children and adolescents represents a great challenge to all medical disciplines concerned; therefore, an interdisciplinary collaboration is indispensable. DIAGNOSTICS: Medicolegal experts require specific radiological examination methods for the differentiation between accidental and non-accidental injuries, depending on the corresponding point in question. In addition, a clear and structured radiological appraisal of the findings is necessary. On the other hand, radiologists require an appropriate succinctly phrased question from the medicolegal expert. PRACTICAL RECOMMENDATIONS: A close collaboration between radiologists and medicolegal experts is mandatory for a better recognition of cases of child abuse; therefore, the joint establishment of diagnostic standards and a comprehensive implementation is necessary.

Multi-energy reconstructions, central electron temperature measurements, and early detection of the birth and growth of runaway electrons using a versatile soft x-ray pinhole camera at MST.

A multi-energy soft x-ray pinhole camera has been designed, built, and deployed at the Madison Symmetric Torus to aid the study of particle and thermal transport, as well as MHD stability physics. This novel imaging diagnostic technique employs a pixelated x-ray detector in which the lower energy threshold for photon detection can be adjusted independently on each pixel. The detector of choice is a PILATUS3 100 K with a 450 µm thick silicon sensor and nearly 100 000 pixels sensitive to photon energies between 1.6 and 30 keV. An ensemble of cubic spline smoothing functions has been applied to the line-integrated data for each time-frame and energy-range, obtaining a reduced standard-deviation when compared to that dominated by photon-noise. The multi-energy local emissivity profiles are obtained from a 1D matrix-based Abel-inversion procedure. Central values of Te can be obtained by modeling the slope of the continuum radiation from ratios of the inverted radial emissivity profiles over multiple energy ranges with no a priori assumptions of plasma profiles, magnetic field reconstruction constraints, high-density limitations, or need of shot-to-shot reproducibility. In tokamak plasmas, a novel application has recently been tested for early detection, 1D imaging, and study of the birth, exponential growth, and saturation of runaway electrons at energies comparable to 100 × Te,0; thus, early results are also presented.

Expression of Hugl-1 is strongly reduced in malignant melanoma.

The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelial-mesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.

A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production.

Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.

Prolactin and glucocorticoid hormones control transcription of the beta-casein gene by kinetically distinct mechanisms.

Transcription of the beta-casein milk protein gene in the HC11 mouse mammary epithelial cell line is induced synergistically by the hormones glucocorticoid and PRL. Sequential treatment of HC11 cells with glucocorticoid and PRL demonstrated that the two hormones had different modes of action on beta-casein transcription. Pretreatment with dexamethasone enhanced the response to subsequent induction by PRL, but not vice versa. Dexamethasone increased the sensitivity of the cells to respond to PRL. The increase in sensitivity was slow, extended for 16 days, and could be rapidly reversed by withdrawal of dexamethasone. The dexamethasone-induced sensitivity for the rapid transcriptional regulation by PRL could be observed with transfected rat beta-casein promoter-chloramphenicol acetyltransferase constructs retaining only 175 basepairs upstream from the transcription initiation site. Expression of the endogenous mouse beta-casein gene was regulated identically to that of the promoter constructs with respect to the synergy of the hormones and their different kinetics of action. In contrast to the slow induction of sensitivity toward PRL, dexamethasone rapidly induced the transcription of a mouse mammary tumor virus long terminal repeat controlled gene in HC11. This demonstrated a normal transcriptional activation of the glucocorticoid receptor in this cell line. Thus, glucocorticoid may regulate beta-casein gene transcription indirectly, inducing or repressing other glucocorticoid-regulated genes, whereas the interaction of PRL with its receptor causes a rapid induction of the beta-casein gene promoter.

Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as well as local signals cooperate in the in vitro regulation of MGF activity.

Neu differentiation factor/heregulin modulates growth and differentiation of HC11 mammary epithelial cells.

The HC11 mouse mammary epithelial cell line has proven to be a valuable in vitro model to study the roles of peptide factors and hormones involved in the growth and differentiation of mammary cells. Treatment of HC11 cells with the lactogenic hormones, dexamethasone, insulin, and PRL (DIP), leads to cellular differentiation and production of the milk protein beta-casein. We have analyzed the effects of Neu differentiation factor (NDF)/heregulin, a newly described activating ligand for erbB-2 and other members of the epidermal growth factor (EGF) receptor family, on cell growth and the expression of milk proteins in HC11 cells. In these cells, NDF induces tyrosine phosphorylation of erbB-2 and erbB-3. Both NDF and EGF stimulate HC11 cell proliferation and promote the responsiveness of HC11 cells to lactogenic hormones. NDF induces the expression of a 22-kilodalton milk protein. This protein is up-regulated by other factors, including dexamethasone, EGF, and basic fibroblast growth factor, and is controlled in a manner distinct from that of beta-casein. Like EGF, NDF inhibits the DIP-induced expression of beta-casein at the level of transcription. The inhibition is due to the negative effect of NDF on the activation of mammary gland factor (MGF/Stat5), a member of the Stat family of transcription factors, which is essential for beta-casein gene expression.

Benzodiazepine antagonist Ro 15-1788 in self-poisoning. Diagnostic and therapeutic use.

Thirteen patients with benzodiazepine overdosage received the specific benzodiazepine antagonist Ro 15-1788. Intravenous administration of 1.5 to 10 mg reversed the central nervous system depression induced by different benzodiazepine compounds within one to two minutes of injection. These case reports indicate that Ro 15-1788 may be an effective tool in the primary management of self-poisoning.

The relaxant and spasmogenic effects of some xanthine derivatives acting on guinea-pig isolated trachealis muscle.

1. Caffeine (10 mM)-induced relaxation of guinea-pig isolated trachealis was attenuated and converted to a small spasmogenic response on cooling to 22 degrees C. The relaxant response was restored on rewarming to 37 degrees C and was abolished by indomethacin (2.8 microM). Cooling to 22 degrees C in the presence of indomethacin revealed spasmogenic responses to caffeine which were abolished on rewarming to 37 degrees C. 2. Trachealis treated with indomethacin (2.8 microM) was repeatedly dosed with acetylcholine (ACh, 10 microM). Caffeine (1 or 10 mM), added as each ACh-induced spasm reached equilibrium, transiently augmented but then suppressed the spasm. On cooling from 37 degrees C to 12 degrees C, the increment in spasm evoked by caffeine increased relative to the spasm evoked by ACh. 3. Trachealis treated with indomethacin (2.8 microM) was repeatedly dosed with caffeine (10 mM). At 37 degrees C caffeine had little effect but it caused spasm when the tissue was cooled to 32 degrees C. Spasm amplitude increased as cooling progressed to 12 degrees C. Similar results were obtained with caffeine (1 mM). 4. At 37 degrees C, caffeine, enprofylline, 1,3,7,9-tetramethylxanthinium (TMX), theobromine, theophylline, xanthine and forskolin each caused concentration-dependent suppression of tracheal tone. Among the xanthine derivatives the rank order of potency was enprofylline greater than theophylline greater than caffeine greater than theobromine greater than xanthine greater than TMX. 5. In trachealis treated with indomethacin (2.8 microM) and maintained at 12 degrees C, the xanthines each caused concentration-dependent spasm. The rank order of potency was theobromine greater than or equal to theophylline greater than or equal to caffeine greater than or equal to enprofylline greater than xanthine greater than TMX. Forskolin was devoid of spasmogenic activity. 6. Trachealis treated with indomethacin (2.8 microM) and maintained at 12 degrees C, was repeatedly dosed with either caffeine (10 mM) or potassium chloride (KCl, 40 mM). Caffeine-induced spasm was attenuated in a Ca2+-free medium containing EGTA (2 mM), modestly at first but subsequently more profoundly. KCl did not evoke spasm at 12 degrees C but at 37 degrees C the KCl-induced spasm was virtually abolished at its first trail in the Ca2+-free, EGTA-containing medium. 7. It is concluded that caffeine, other alkylated xanthines and xanthine itself share a spasmogenic action in guinea-pig isolated trachealis which is best observed when the tissue is treated with indomethacin (2.8 microM) and maintained at 12 degrees C. The spasmogenic action represents the release of Ca2+ from intracellular sites of sequestration and may not depend on the intracellular accumulation of cyclic AMP. The rank order of spasmogenic potency of the xanthine derivatives differs markedly from their rank order of potency in suppressing the spontaneous tone of the trachealis observed at 370C. Since, at 12 degrees C, TMX is spasmogenic at concentrations identical to those causing relaxation at 37 degrees C, it is likely that TMX penetrates the cell. The relaxant effects of TMX do not, therefore, indicate that methylxanthine-induced relaxation is mediated by a receptor located on the external surface of the cell.

Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylates. Direct evaluation with electron spin resonance spectroscopy.

Reactive oxygen radicals such as superoxide and hydroxyl radicals, as well as intermediate unsaturated fatty acid radicals, have been proposed as playing an important role in various diseases including inflammatory bowel disease (IBD). In this study we evaluated radical scavenger properties of aminosalicylates used in the therapy of IBD using spin trapped electron spin resonance spectroscopy. 5-Aminosalicylic acid (5-ASA), 4-aminosalicylic acid and olsalazine had superoxide radical scavenger properties (IC50 = 0.4, 0.4 and 1.0 mM, respectively). 5-ASA and benzalazine also inhibited hydroxyl radicals (IC50 = 6.5 mM). Fatty acid radicals were not inhibited by aminosalicylates. Our results support the hypothesis that therapeutically active compounds may be oxygen radical scavengers and that fatty acid radical scavenging has to be performed by drugs other than aminosalicylates.

Overexpression of the glucocorticoid receptor represses transcription from hormone responsive and non-responsive promoters.

The glucocorticoid receptor (GR) is a regulable transcription factor which can bind to DNA response elements in the vicinity of inducible gene promoters and enhance the rate of transcription initiation. The concentration of endogenously expressed GR has been shown to limit the magnitude of the transcriptional induction response in cultured cells. We have investigated the consequence of increased GR expression on the transcriptional activity of a hormone responsive promoter, the MMTV LTR, and on three non-responsive promoters, the RSV LTR, the SV40 early promoter and the c-fos promoter in transiently transfected cells. Low receptor concentrations allow a slight hormonal induction of the MMTV LTR while maximal inducibility can be observed at intermediate GR concentrations. High GR expression reduces the hormonal induction on the MMTV LTR and also adversely effects transcription from the RSV LTR, the SV40 and c-fos promoters. This repression effect is dependent on GR activation. These experiments suggest that the GR interacts with a nuclear factor that is required for the activation of all four promoters. It is probable that "squelching", i.e. protein-protein complex formation in the nucleus leads to the sequestration of interacting proteins(s) essential for the transcription machinery, causing a limitation for the initiation events.

Electric-field induced effects in acetylcholinesterase.

Acetylcholinesterase from Torpedo marmorata Risso was adsorbed as a monolayer on to a germanium internal reflection plate. The behaviour of the enzyme in strong electric fields was investigated by means of infrared attenuated total reflection (ATR) spectroscopy. A positive potential on the germanium plate was found to result in an electric-field induced dissociation of the -COOH groups of Asp and Glu residues. Independently, a field-induced conformational change of the protein was observed. Since a negative charge on the enzyme facilitates the trapping of positively charged acetylcholine, and this negative charge can be controlled via the potential of the support to which it is adsorbed, a new electrostatic regulation model for acetylcholinesterase activity in excitable membranes is proposed.

Intracardiac malpositioning of a sternoclavicular fixation wire.

A case of intracardiac malpositioning of a sternoclavicular Kirschner pin is reported. After an uneventful closed wire-fixation of sternoclavicular subluxation and a normal postanesthetic recovery, a 17-year-old male patient developed opacification of the right hemithorax and signs of internal bleeding. The lateral chest roentgenogram showed one fixation wire protruding deeply into the anterior mediastinum. Sternotomy showed a large pericardial tear communicating with the right pleural cavity and a puncture hole of the right auricle that had caused a blood loss of 3 L into the pleural space. Although the surgical repair was uneventful, the patient eventually died as a sequelae to prolonged cerebral hypoxemia.

[The value of prenatal ultrasound screening exemplified by abnormalities of the urogenital system. Data from the Styrian malformation register 1985 to 1987]. / Der Wert des pränatalen Ultraschall-Screenings am Beispiel von Fehlbildungen des Urogenitalsystems. Daten aus dem Steirischen Fehlbildungsregister 1985 bis 1987.

Over a three-year period (1985 to 1987), the number of fetal malformations was entered into Styrian Malformation Register (SMR). The data were compared with those of the Austrian Ministry of Health. The SMR collected 137 cases of urinary tract malformations, but only six appeared in the Health Ministry statistics. This discrepancy resulted from the different data collection methods. Presently only a small percentage of fetal abnormalities is officially registered. Using the example of urinary tract malformations this paper shows the value of prenatal ultrasound screening. Such infants must be treated soon after delivery to avoid progression of parenchymal damage. Ultrasound examinations should not be restricted to pregnant women at defined risk. Registration of all prenatally diagnosed--or missed--malformations is a quality-control measurement and improves prenatal diagnosis.

Regional long-term co-operation in the field of nuclear and radiation emergency preparedness.

Emergency preparedness is generally covered by methodical and coordinative activities of the International Atomic Energy Agency (IAEA) in Member States of the IAEA and by the European Commission (EC) in EU Member and EU Accession Countries. However, the regional harmonisation of emergency arrangements is an important trend of emergency preparedness. The present paper gives a couple of illustrative examples for a regional co-operation in the field of emergency preparedness in Central Europe and an overview on international exercises in this region. The penultimate section contains an outlook on future activities regarding regional co-operation in Central Europe. The following topics have been suggested inter alia: the harmonisation of intervention criteria and countermeasures, co-ordination in the field of information of the public, comprehensive bi lateral and multilateral exercises, exchange of experts between the national nuclear emergency centres and inter-comparison calculations of the computer codes.

The Austria-Czech Republic co-operation in the field of radiation-emergency preparedness.

An overview on the long-term information exchange and co-operation between Austria and the Czech Republic in the field of radiation emergency preparedness and evaluation of radiological consequences of NPP accidents is provided. Initiated by the 'Melk Protocol' between the Czech and Austrian governments in December 2000 and its follow-up activities, the information exchange and co-operation between the Czech Republic and Austria in the field of radiation-emergency preparedness have been extended. Among others, a Working Group to compare radiological consequences of Beyond Design Basis Accident with a detailed inter-comparison program concerning atmospheric dispersion models, dose assessment methods and counter- measures was established. Based on this experience, an area for future co-operation in the field of emergency preparedness and information exchange between the Czech Republic and Austria is discussed.

Novel energy resolving x-ray pinhole camera on Alcator C-Mod.

A new energy resolving x-ray pinhole camera has been recently installed on Alcator C-Mod. This diagnostic is capable of 1D or 2D imaging with a spatial resolution of ≈1 cm, an energy resolution of ≈1 keV in the range of 3.5-15 keV and a maximum time resolution of 5 ms. A novel use of a Pilatus 2 hybrid-pixel x-ray detector [P. Kraft et al., J. Synchrotron Rad. 16, 368 (2009)] is employed in which the lower energy threshold of individual pixels is adjusted, allowing regions of a single detector to be sensitive to different x-ray energy ranges. Development of this new detector calibration technique was done as a collaboration between PPPL and Dectris Ltd. The calibration procedure is described, and the energy resolution of the detector is characterized. Initial data from this installation on Alcator C-Mod is presented. This diagnostic provides line-integrated measurements of impurity emission which can be used to determine impurity concentrations as well as the electron energy distribution.

Inpatient treatment of major depression in Austria between 1989 and 2009: impact of downsizing of psychiatric hospitals on admissions, suicide rates and outpatient psychiatric services.

BACKGROUND: During the last 20 years Austrian psychiatric services underwent fundamental changes, as a focus was set on downsizing psychiatric hospitals. Little is known about how restructuring of mental health services affected patients with major depression and suicide rates. METHODS: Monthly hospital discharges from all hospitals in Austria with the diagnosis of unipolar major depression as primary reason for inpatient treatment were obtained for the time period between 1989 and 2008. These data were correlated with relevant parameters from the general health system, such as number of hospital beds, suicide rate, density of psychotherapists and sales of antidepressants. RESULTS: While the number of psychiatric beds was reduced by almost 30%, the total annual numbers of inpatient treatment episodes for depression increased by 360%. This increase was stronger for men than for women. Further on this development was accompanied by a decrease in the suicide rate and an improvement in the availability of professional outpatient mental health service providers. LIMITATIONS: Only aggregated patient data and no single case histories were available for this study. The validity of the correct diagnosis of unipolar major depression must be doubted, as most likely not all patients were seen by a clinical expert. CONCLUSIONS: Our data show that although inpatient treatment for unipolar major depression dramatically increased, reduction of psychiatric beds did not lead to an increase of suicide rates.

The impact of temperament in the course of alcohol dependence.

AIMS: The aim of this study was to assess the impact of temperamental traits in alcohol dependent patients on the course of illness. METHODS: The case files of 116 alcohol dependent patients, according to ICD-10 and DSM-IV-TR, were examined retrospectively. All patients were in treatment between 02/08 and 03/09 at the Psychiatric Department of the General Hospital Vienna, either at the alcohol outpatient clinic or the psychiatric ward, which has the treatment focus on alcohol dependence. The brief TEMPS-M auto-questionnaire was used to assess the temperamental distribution. The dimensions of alcohol dependence have been assessed using the Lesch Alcoholism Typology, a computerized structured interview. The potential effect of temperamental scores on various outcomes describing the course of illness is investigated using multi-variable regression models. RESULTS: Cyclothymic score was the only temperament which significantly influenced the age of onset of alcohol abuse and age of onset of alcohol dependence. Backward selection among temperaments exhibits depressive temperament as most important effect regarding the likelihood of suicide-attempts in the patient's case history and anxious temperament as most important effect regarding having psychiatric treatment focusing on alcohol dependence prior to current in- or outpatient stay. LIMITATIONS: The sample size of this study is small compared to the number of investigated outcomes and temperaments. Further, a healthy control group, matched for age and gender, was not available for comparison of the temperament sub-scores. CONCLUSION: Dominant cyclothymic, but also depressive and anxious temperament, seem to be negative predictors for the course of illness in alcohol dependence. Regarding positive long term outcome specific evidence based medical treatment approaches are needed for these patients.