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.

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.

[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.

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.

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.

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.

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.

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.

The stromal reaction in basal cell carcinomas. A prerequisite for tumour progression and treatment strategy.

Specimens of basal cell carcinomas collected from 28 patients were classified into three groups: superficial, nodular, and infiltrative, according to their microarchitecture. The specimens were then subjected to histological characterization by means of a biotinylated hyaluronan-binding probe (HABP). By using Ki-67 and PCNA the proliferative activity of the BCC tumours was evaluated with immunohistological techniques. In superficial BCC the tumour islands displayed moderate hyaluronan (HA) staining. Feeble proliferation, denoted by modest mitotic activity and weak Ki-67 and PCNA immunoreactivity, occurred within the tumour islands. The surrounding connective tissue resembled normal skin, and no differentiated tumour stroma was observed. In nodular BCC, the HA staining of the tumour strands was weak to moderate, denoting increased proliferative activity. The differentiated surrounding tumour stroma stained strongly for HA. Tumour islands of infiltrative BCC stained weakly to moderately to HA and evidenced intense proliferation. The intensely HA-stained tumour stroma ended abruptly and the adjacent areas were almost devoid of HA. This study showed that the proliferative activity of BCC cells is associated with increased expression of HA in the tumour stroma. Modification of tumour-associated connective tissue indicates a close relationship between the tumour cells and the adjacent matrix. In particular, in infiltrative BCC, such alterations include degeneration and possible modification and remodelling of the surrounding extracellular matrix. These processes involving areas of probable importance for tumour progression, should be considered when deciding the extent of intended surgical resection.

Exchange of three amino acids in the coat protein results in efficient whitefly transmission of a nontransmissible Abutilon mosaic virus isolate.

Geminiviruses are transmitted in a circulative manner by whiteflies, leafhoppers, or treehoppers. The whitefly species Bemisia tabaci (Genn.) is the vector for members of the genus Begomovirus. The closely related bipartite Central American begomoviruses Abutilon mosaic virus (AbMV), Sida golden mosaic virus originating from Costa Rica (SiGMV-CR), and Sida golden mosaic virus originating from Honduras (SiGMV-Hoyv) were used to study transmission by their insect vector. The AbMV isolate is defective in transmission, whereas the two Sida-infecting viruses are readily transmitted by B. tabaci. These three viruses are able to form pseudorecombinant viruses by exchange of genomic components. The pseudorecombinant virus SiGMV-Hoyv A/AbMV B was transmissible, whereas the reciprocal pseudorecombinant virus AbMV A/SiGMV-Hoyv B was not transmitted, indicating that DNA B is not involved in the transmission defect. However, the uptake of the pseudorecombinant virus AbMV A/SiGMV-Hoyv B was much better than AbMV itself, indicating that DNA B or DNA B gene products enhance uptake of viral DNA. Exchange of AbMV coat protein with that of SiGMV-CR resulted in a transmissible chimeric AbMV. Mutagenesis of the AbMV coat protein showed that the exchange of two amino acids, at positions 124 and 149, was sufficient to obtain a whitefly-transmissible AbMV mutant. However, when amino acid 174 was altered in addition to amino acids 124 and 149 AbMV was readily transmitted by B. tabaci. From this we conclude that it is not a concise motif, such as the amino acid triplet, aspartate-alanine-glycine (DAG), involved in aphid transmission of potyviruses, that determines transmissibility of begomoviruses by B. tabaci. Instead it is the composition of the coat protein domain from amino acid 123 to 149, as a minimal transmission domain, with the contribution of amino acids 149 to 174 for efficient transmission.

Host range and symptom variation of pseudorecombinant virus produced by two distinct bipartite geminiviruses.

Within the whitefly group only the species Bemisia tabaci (Gennadius) is the vector. Most whitefly-transmitted geminiviruses possess bipartite DNA genomes, DNAs A and B. Although they are closely related to each other, the production of viable pseudorecombinants between bipartite geminiviruses by reassortment of infectious cloned components is generally limited to strains of a particular virus. Following exchange of cloned genomic components of Sida golden mosaic virus (SiGMV/Hoyv) and Abutilon mosaic virus (AbMV), the pseudorecombinant viruses were infectious in various host plants. The symptom type of pseudorecombinant virus was in most cases determined by DNA B. However, in some host plants also DNA A of the pseudorecombinant virus was involved in the symptom phenotype.

Coat protein gene replacement results in whitefly transmission of an insect nontransmissible geminivirus isolate.

Geminiviruses are transmitted by whiteflies, leafhoppers, or treehoppers. The whitefly species Bemisia tabaci (Gennadius) is the most efficient vector of Subgroup III geminiviruses. An isolate of Abutilon mosaic virus (AbMV), a bipartite geminivirus, was not detectable in the DNA extract from insects by Southern blot analysis, nor was the isolate transmissible by the B-biotype of B. tabaci, although the virus DNA was amplified (by PCR) from some insects. In contrast, Sida golden mosaic virus (SiGMV-Co), a closely related geminivirus, was acquired and transmitted by B. tabaci to various host plants. The coat protein of AbMV was replaced with that of SiGMV-Co. The resulting chimeric AbMV was acquired and transmitted to various host plants by B. tabaci, indicating that the coat protein plays an essential role in the transmission process by B. tabaci.

Nucleotide sequence of a new bipartite geminivirus isolated from the common weed Sida rhombifolia in Costa Rica.

The nucleotide sequence of infectious clones of a geminivirus from Costa Rica that infects Sida rhombifolia was determined. Sida golden mosaic virus (SiGMV-Co) has a bipartite genome (DNAs A and B). Computer analysis showed that the bipartite genome of SiGMV-Co resembles that of other whitefly-transmitted geminiviruses. The DNA A (2605 nt) and DNA B (2587 nt) components have little sequence homology other than within the common region (CR). Analysis of DNAs A and B showed that SiGMV-Co is closely related to bean dwarf mosaic virus (BDMV). SiGMV-Co was introduced via agroinoculation into seven plant species, including tomato and bean.

Is vulvar vestibulitis an inflammatory condition? A comparison of histological findings in affected and healthy women.

Vulvar vestibulitis, as defined by Friedrich, is considered to be inflammatory, despite the fact that the normal histology of this specific area has previously not been characterized. The aim of the present study was to compare the normal histology of the vulvar vestibulum with findings in localized vulvar vestibulitis. Biopsies were taken at the area of the vestibulitis, i.e. at the openings of the Bartholin's duct. Eleven control specimens were examined histologically and compared to 24 specimens obtained from 20 patients. All samples were also tested for human papillomavirus, and they were all negative. In control specimens, as well as in specimens from patients, subepithelial inflammatory cells, sometimes aggregated into lymph follicles and/or small groups of lymphocytes were found. The conclusion is reached that the occurrence of inflammatory cells in vestibular tissue is a normal finding and cannot serve as a histological indicator of vulvar vestibulitis.

Negative modulation of membrane localization of the Raf-1 protein kinase by hyperphosphorylation.

The serine/threonine-specific protein kinase Raf-1 plays a key role in mitogenic signal transduction by coupling Ras to the mitogen-activated protein (MAP) kinase cascade. Ras-mediated translocation to the plasma membrane represents a crucial step in the process of serum-stimulated Raf-1 kinase activation. The exact role of the multisite phosphorylation in Raf regulation, however, is not clear. We have previously reported that the mobility shift-associated hyperphosphorylation of Raf correlates with a reduction of serum-stimulated Raf kinase activity (Wartmann, M., and Davis, R. J. (1994) J. Biol. Chem. 269, 6695-6701). Here we show that incubation of serum-starved CHO cells with D609, a purported inhibitor of phosphatidylcholine-specific phospholipase C, also results in a mobility shift of Raf-1 that is due to hyperphosphorylation on sites identical to those observed following mitogen stimulation. Subcellular fractionation analyses revealed that D609-induced mobility shift-associated hyperphosphorylation was paralleled by a decreased membrane association of Raf-1. Similar results were obtained in an in vitro reconstitution system. Furthermore, PD98059, a specific inhibitor of activation of the MAP kinase kinase MEK, prevented D609-induced Raf hyperphosphorylation and restored the amount of membrane-bound Raf to control levels. Taken together, these data suggest that mobility shift-associated hyperphosphorylation of Raf-1, by virtue of reducing the amount of plasma membrane-bound Raf-1, represents a negative feedback mechanism contributing to the desensitization of the MAP kinase signaling cascade.

Lactogenic hormone activation of Stat5 and transcription of the beta-casein gene in mammary epithelial cells is independent of p42 ERK2 mitogen-activated protein kinase activity.

HC11 mammary epithelial cells have been used to characterize molecular events involved in the regulation of milk protein gene expression. Treatment of HC11 cells with the lactogenic hormones prolactin, insulin, and glucocorticoids results in transcription of the beta-casein gene. Prolactin induces a signaling event which involves tyrosine phosphorylation of the mammary gland factor, Stat5, a member of the family of signal transducers and activators of transcription (Stat). Here we show that HC11 cells express two Stat5 proteins, Stat5a and Stat5b. Phosphopeptide and phosphoamino acid analysis of Stat5a and Stat5b immunoprecipitated from phosphate-labeled HC11 cells revealed that both proteins were constitutively phosphorylated on serine. Lactogenic hormone treatment resulted in the appearance of a tyrosine-phosphorylated peptide in both Stat5 proteins. Consistent with this observation, a Western blot analysis of Stat5a and Stat5b showed that lactogenic hormones induced a rapid, transient increase in phosphotyrosine which paralleled the binding of Stat5 to its cognate recognition sequence in the beta-casein gene promoter. Lactogenic hormone treatment of the HC11 cells also led to a rapid activation of the mitogen-activated protein (MAP) kinase pathway. We examined the role of this pathway in beta-casein transcription using a specific MAP kinase kinase inhibitor, PD98059. Concentrations of PD98059 which completely abrogated lactogen-induced MAP kinase activation did not affect the phosphorylation state of Stat5, its DNA binding activity, or transcriptional activation of a beta-casein reporter construct. This indicates that the MAP kinase pathway does not contribute to lactogenic hormone induction of the beta-casein gene.

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.

The gene for diffuse palmoplantar keratoderma of the type found in northern Sweden is localized to chromosome 12q11-q13.

Hereditary palmoplantar keratoderma is characterized by hyperkeratosis of the skin of palms and soles. An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, frequently complicated by fungal infections, is encountered in northern Sweden with a prevalence of 0.3-0.55%. We have examined two families with this type of palmoplantar keratoderma and localized the causative genetic defect to a 14 cM interval on chromosome 12q11-q13, a region known to contain the keratin type II gene cluster as well as the retinoic acid receptor gamma gene. The palmoplantar keratoderma variant investigated in this study is thus genetically different from epidermolytic palmoplantar keratoderma, which recently has been shown to result from mutations in the gene for the type I keratin 9.