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[Urinary tract injuries in polytraumatized patients].

BACKGROUND: Within the S3 Guideline Project of the European Association of Urology (EAU) an expert committee was set up to develop guidelines for the appropriate management of genitourinary trauma. These European guidelines were accepted in principle as national guidelines by the German Urological Society. Therefore, they also became the basis of the contribution of the German Urological Society to the S3 Guideline Project "Polytrauma" of the German Society for Trauma Surgery. METHOD: For the guideline "management of genitourinary trauma" all the requirements for classification as S3 guidelines were full-filled. The guideline itself was developed in accordance with the principles of "evidence-based medicine". A systematic analysis of literature published between 1966 and 2004 was carried out. The articles retrieved were assessed in respect of study design and clinical relevance and classified following the scheme of the Centre for Evidence-Based Medicine in Oxford. CONCLUSION: In suspected renal injuries the hemodynamic situation of the patient is the benchmark for the diagnostic and therapeutic algorithm. The diagnostic gold standard for the assessment of haemodynamically stable patients is CT scanning. Uncontrolled haemodynamic instability is an indication for immediate explorative laparotomy. Partial ureteral tears are managed by stenting; complete tears by immediate surgical repair. Pelvic fractures are often associated with bladder ruptures. Extraperitoneal bladder ruptures, identified by retrograde cystography, are in most cases safely managed by simple catheter drainage. Intraperitoneal ruptures require surgical intervention. Blood at the meatus may suggest a urethral lesion-blind urethral catheterization should not be attempted. Suprapubic cystostomy and delayed urethroplasty are recommended.

Germany↗

[Injuries of parasagittal bridging veins in fatally wounded victims of motor vehicle accidents].

Experimental data and clinical as well as postmortem experiences have indicated that subdural hematomas are less frequent in acceleration injuries in traffic accidents compared to falls or assaults. The present report demonstrates that this does not hold true in the same way for bridging vein ruptures (one of the predominant causes for subdural bleedings). Ruptures of these vessels without subdural bleeding (SDB) are only seldom mentioned in the literature. However, if no SDB is present, no one will look for these structures. In our institute a systematic analysis of the bridging veins in all cases of lethal blunt head injury is made: prior to the careful morphological preparation we investigate these vessels by radiographic imaging after filling with contrast medium. 6 car passengers (age between 4 and 31 years) which suffered a lethal head injury were examined in the last year. 2 victims had impressed fractures with cerebral compression injuries. In 1 case the base of the skull was broken and in 3 cases no skull fracture was present; no serious focal brain injury had occurred in these 4 cases, but 3 victims had signs of diffuse brain injury. In 5 cases a direct impact of the head against the interior of the car was obvious. In 5 cases ruptures of several bridging veins could be demonstrated. In one case (survival for 3 days) a minor SDB (20 ml) was present and the ruptures had been closed by thrombosis; another victim died at the scene. The other 3 victims survived between 4 and 15 hours without developing SDB and without closing of the ruptures by thrombosis. This combination is surprising and shows that our knowledge concerning the relationship between bridging vein ruptures and SDB is restricted. The frequency of bridging vein lesions in severe head injuries is likely underestimated in the clinical as well as in the postmortem literature. A rapid increase of intracranial pressure after the accident resulting in a collapse of the cerebral circulation is probably responsible for the absence of the SDB in the presented cases.

Accidents, Traffic↗

[Victims of Nazi euthanasia, the so-called T4 action. First results of a project at the German Federal Archives to disclose records of killed patients].

In 1990, previously unknown documents dated from the Nazi era were found in Berlin. They had been preserved in the central archives of the Ministry for State Security (MfS), the secret service of the now former German Democratic Republic (GDR). Nearly 30,000 psychiatric patient files turned out to comprise the smaller part of the records of patients who had been murdered in the 1940/41 "T4 action". More than 70,000 patients of psychiatric asylums were killed by gas in this first campaign of extermination during Nazism, and their files were believed to have been lost. Based on a project to be funded by the German Research Association, this paper offers a brief survey of the developments in historical research about Nazi "euthanasia" and the theories interpreting historical information. The paper will also present a research project dedicated to the memory of the victims of the "T4 action" and to the rediscovered files now conserved in the German Federal Archives in Berlin. The aim is to offer a systematic analysis of 3,000 records in an effort to contribute to the perception of the victims as individuals. The analysis will also include an examination of the selection criteria stipulated by the Nazi psychiatrists (hereditary illness, incurability, and incapacity to work productively) to select patients for extermination. In this way, the decision-making process, criteria, and motives that led to the killing should become more clear. This empirical analysis will help to answer questions concerning the proportion of eugenic and economic motivations and the Nazi rationale behind the extermination campaigns. The project will build upon an earlier preliminary study of a nonrepresentative sample of 185 files. As a preliminary result, it can be said that most of the victims had been hospitalised over long terms and classified as schizophrenic or feeble-minded. A third of the patients killed were considered invalid and not working, and almost 50% were described as working "mechanically". Five per cent of the victims were working "productively".

Crime Victims↗

[The effectiveness of atomoxetine in children, adolescents, and adults with ADHD. A systematic overview].

This paper gives an overview of the pharmacology, efficacy, duration, tolerance, and side effects of atomoxetine for children, adolescents, and adults. A systematic analysis of the published clinical studies and poster abstracts was conducted. Atomoxetine is the first selective inhibitor of the noradrenaline transporter that was approved by the FDA in the US as a nonstimulant for the treatment of ADHD in children, adolescents, and adults. In clinical studies, its efficacy was studied in 4,000 patients. Compared with placebo, atomoxetine proved to be superior with respect to reducing impulsiveness, hyperactivity, and inattention. There are indications that its efficacy is comparable to that of methylphenidate. In general, atomoxetine was well tolerated. The most frequently reported adverse events were decrease of appetite, abdominal problems, tiredness, and vertigo. These were classified as mild and found mostly at the beginning of treatment. The existing results indicate that atomoxetine is promising for the treatment of ADHD in children, adolescents, and adults.

Adolescent↗

[Molecular diagnostics of prostate cancer].

Although a number of studies have identified molecular markers for prostate cancer, their clinical utility remains mainly unclear. Markers, which allow improved determination of the biological aggressiveness of individual prostate cancers, may help to optimize therapeutic management of this heterogeneous tumor type. Here, a subset of molecular markers, which are intensively discussed in the literature or which are supposed to gain clinical utility in the future, are described in more detail. For a better survey, the markers are divided into (a) susceptibility markers, (b) malignancy markers, and (c) aggressiveness markers. The number of markers described as well as the inconsistency across studies in assessing their clinical utility reflect the heterogeneity of prostate cancer also on a genetic level so that it is unlikely that a single marker will gain clinical relevance. Future research must include systematic analysis of the clinical utility of not only single markers but rather of marker profiles in appropriate studies.

Genetic Markers↗

Compulsory admission of mentally ill patients in European Union Member States.

BACKGROUND AND AIMS: A standardised and systematic analysis of commitment laws in the European Union Member States is still missing. This study aimed at gathering, describing and analysing information on the differences or similarities of legal frameworks for involuntary placement and treatment of mentally ill patients across the European Union Member States. METHOD: Information was gathered by means of a detailed questionnaire filled in by experts from all EU Member States. Legal criteria for compulsory admission and details of the assessment and decision process of compulsory admission are outlined. RESULTS: Although common patterns among Member States can be identified upon comparison of crucial legislative or procedural details, these patterns are far from being consistent across all analysed items or approaches. With regard to compulsory admission quotas no significant influence of legal commitment criteria and the involvement of judicial authorities could be found, but Member States with an obligatory inclusion of a legal representative during the commitment procedure showed significantly lower compulsory admission quotas. CONCLUSION: Results of this study show the strong necessity for further research in this field. Common international health reporting standards as annually updated involuntary placement rates detailed for regular and emergency cases seem to be essential.

Commitment of Persons with Psychiatric Disorders↗

Hypothermia in the management of traumatic brain injury. A systematic review and meta-analysis.

OBJECTIVE: Brain injury remains the leading cause of death in cases of trauma in North America and Europe. This article critically appraised and summarised all published and peer-reviewed, randomised, controlled trials of the use of hypothermia in traumatic brain injury. DESIGN: To be included, a study had to be a published, randomised, controlled trial of the use of hypothermia in the management of traumatic brain injury. Pooling of data and meta-analysis of results occurred. SETTING: Conducted at a tertiary level Canadian teaching hospital. PATIENTS AND PARTICIPANTS: Patients were combined from eight randomised, controlled trials to generate a population of 748 severely head-injured patients. MEASUREMENTS AND RESULTS: Eight studies provided data on the efficacy of hypothermia in the management of traumatic brain injury. The pooled odds ratio of mortality in the hypothermic group was 0.81 (95%CI =0.59-1.13, p=0.22). The OR of a poor neurological outcome (GOS 1,2 or 3) was 0.75 (95% CI=0.56-1.01, p=0.06). The odds ratio for pneumonia in the normothermic group was 0.42 (95%CI =0.25-0.70, p=0.001). CONCLUSIONS: Although meta-analysis suggests that iatrogenic hypothermia may confer a marginal benefit in neurological outcome, there does not appear to be clear evidence of lower mortality rates in unselected traumatic brain injury patients. Prolonged hypothermia may confer a benefit, particularly in patients with elevated intracranial pressure refractory to conventional manipulations. Conclusions regarding the use of hypothermia are controversial and not strongly supported by the available evidence.

Brain Injuries↗

Spatial characteristics of neurons in the central mesencephalic reticular formation (cMRF) of head-unrestrained monkeys.

Prior studies of the central portion of the mesencephalic reticular formation (cMRF) have shown that in head-restrained monkeys, neurons discharge prior to saccades. Here, we provide a systematic analysis of the patterns of activity in cMRF neurons during head unrestrained gaze shifts. Two types of cMRF neurons were found: presaccadic neurons began to discharge before the onset of gaze movements, while postsaccadic neurons began to discharge after gaze shift onset and typically after the end of the gaze shift. Presaccadic neuronal responses were well correlated with gaze movements, while the discharge of postsaccadic neurons was more closely associated with head movements. The activity of presaccadic neurons was organized into gaze movement fields, while the activity of postsaccadic neurons was better organized into movement fields associated with head displacement. We found that cMRF neurons displayed both open and closed movement field responses. Neurons with closed movement fields discharged before a specific set of gaze (presaccadic) or head (postsaccadic) movement amplitudes and directions and had a clear distal boundary. Neurons with open movement fields discharged for gaze or head movements of a specific direction and also for movement amplitudes up to the limit of measurement (70 degrees). A subset of open movement field neurons displayed an increased discharge with increased gaze shift amplitudes, similar to pontine burst neurons, and were called monotonically increasing open movement field neurons. In contrast, neurons with non-monotonically open movement fields demonstrated activity for all gaze shift amplitudes, but their activity reached a plateau or declined gradually for gaze shifts beyond specific amplitudes. We suggest that presaccadic neurons with open movement fields participate in a descending pathway providing gaze signals to medium-lead burst neurons in the paramedian pontine reticular formation, while presaccadic closed movement field neurons may participate in feedback to the superior colliculus. The previously unrecognized group of postsaccadic cMRF neurons may provide signals of head position or velocity to the thalamus, cerebellum, or spinal cord.

Action Potentials↗

Surviving high-intensity field pulses: strategies for improving robustness and performance of electrotransfection and electrofusion.

Electrotransfection and electrofusion, both widely used in research and medical applications, still have to face a range of problems, including the existence of electroporation-resistant cell types, cell mortality and also great batch-to-batch variations of the transfection and fusion yields. In the present study, a systematic analysis of the parameters critical for the efficiency and robustness of electromanipulation protocols was performed on five mammalian cell types. Factors examined included the sugar composition of hypotonic pulse media (trehalose, sorbitol or inositol), the kinetics of cell volume changes prior to electropulsing, as well as the growth medium additives used for post-pulse cell cultivation. Whereas the disaccharide trehalose generally allowed regulatory volume decrease (RVD), the monomeric sugar alcohols sorbitol and inositol inhibited RVD or even induced secondary swelling. The different volume responses could be explained by the sugar selectivity of volume-sensitive channels (VSC) in the plasma membrane of all tested cell types. Based on the volumetric data, highest transfection and fusion yields were mostly achieved when the target cells were exposed to hypotonicity for about 2 min prior to electropulsing. Longer hypotonic treatment (10-20 min) decreased the yields of viable transfected and hybrid cells due to (1) the cell size reduction upon RVD (trehalose) or (2) the excessive losses of cytosolic electrolytes through VSC (inositol/sorbitol). Doping the plasma membrane with lipophilic anions prevented both cell shrinkage and ion losses (probably due to VSC inhibition), which in turn resulted in increased transfection and fusion efficiencies.

Animals↗

Artiodactyl emergence is accompanied by the birth of an extensive pool of diverse germline TRDV1 genes.

Molecular cloning of cDNA from gamma/delta T cells has shown that in sheep, the variable domain of the delta chain is chiefly determined by the expression of the TRDV1 subgroup, apparently composed of a large number of genes. There are three other TRDV subgroups, but these include only one gene each. To evaluate the extent and the complexity of the genomic TRDV repertoire, we screened a sheep liver genomic library from a single individual of the Altamurana breed and sheep fibroblast genomic DNA from a single individual of the Gentile di Puglia breed. We identified a total of 22 TRDV1 genes and the TRDV4 gene. A sequence comparison between germline and the rearranged genes indicates that, in sheep, the TRDV repertoire is generated by the VDJ rearrangement of at least 40 distinct TRDV1 genes. All germline TRDV1 genes present a high degree of similarity in their coding as well as in 5' and 3' flanking regions. However, a systematic analysis of the translation products reveals that these genes present a broadly different and specific repertoire in the complementarity-determining regions or recognition loops, allowing us to organize the TRDV genes into sets. We assume that selection processes operating at the level of ligand recognition have shaped the sheep TRDV germline repertoire. A phylogenetic study based on a sequence analysis of the TRDV genes from different mammalian species shows that the diversification level of these genes is higher in artiodactyl species compared to humans and mice.

Amino Acid Sequence↗

Comparative delineation of T cell clonotypes in coexisting syngeneic B16 melanoma.

B16 is a murine melanoma of C57B1/6 origin, which rapidly develops as a tumor when inoculated into syngeneic immunocompetent hosts. Nevertheless, B16 tumors are considered to be immunogenic since tumor regression can be induced by means of immunotherapeutic intervention. Furthermore, B16 melanoma cells express several melanoma-associated antigens that may serve as targets for autologous T cells. To study the in vivo T cell response against B16, with particular emphasis on diversity and systemic involvement, we examined the spectra of T cell clonotypes in coexisting B16 melanoma lesions in C57B1/6 mice. Three tumors from each animal (n = 8) were examined for the presence of clonotypic T cells using the highly sensitive T cell receptor (TCR) clonotype mapping technology. Systematic analysis of the TCRB variable regions 1-16 revealed from 19 to more than 30 clonotypic TCR transcripts in each tumor. To study intra- and inter-individual variations in the T cell response further, more than 600 clono-typic TCR transcripts were compared for sequence identity. Overall, approximately 2% of the T cell clonotypes were detected in more than one tumor from the same animal. Furthermore, none of the detected clonotypes was present in more than one animal, arguing against recurrent or "public" T cell responses against B16 melanoma. Our data strongly suggest that anti-melanoma T cell responses in this murine model encompass mainly localized T cells, and that systemic involvement is limited.

Animals↗

Hydrochemical buffer assessment in agricultural landscapes: from local to catchment scale.

Non-point-source pollution of surface and groundwater is a prominent environmental issue in rural catchments, with major consequences on water supply and aquatic ecosystem quality. Among surface-water protection measures, environmental or landscape management policies support the implementation and the management of buffer zones. Although a great number of studies have focused on buffer zones, quantification of the buffer effect is still a recurring question. The purpose of this article is a critical review of the assessment of buffer-zone functioning. Our objective is to provide land planners and managers with a set of variables to assess the limits and possibilities for quantifying buffer impact at the catchment scale. We first consider the scale of the local landscape feature. The most commonly used empirical method for assessing buffers is to calculate water/nutrient budgets from inflow-outflow monitoring at the level of landscape structures. We show that several other parameters apart from mean depletion of flux can be used to describe buffer functions. Such parameters include variability, with major implication for water management. We develop a theoretical framework to clarify the assessment of the buffer effect and propose a systematic analysis taking account of temporal variability. Second, we review the current assessment of buffer effects at the catchment scale according to the theoretical framework established at the local scale. Finally, we stress the limits of direct empirical assessment at the catchment scale and, in particular, we emphasize the hierarchy in hydrological processes involved at the catchment scale: The landscape feature function is constrained by other factors (climate and geology) that are of importance at a broader spatial and temporal scale.

Agriculture↗

Great Basin land management planning using ecological modeling.

This report describes a land management modeling effort that analyzed potential impacts of proposed actions under an updated Bureau of Land Management Resource Management Plan that will guide management for 20 years on 4.6 million hectares in the Great Basin ecoregion of the United States. State-and-transition models that included vegetation data, fire histories, and many parameters (i.e., rates of succession, fire return intervals, outcomes of management actions, and invasion rates of native and nonnative invasive species) were developed through workshops with scientific experts and range management specialists. Alternative restoration scenarios included continuation of current management, full fire suppression, wildfire use in designated fire use zones, wildfire use in resilient vegetation types only, restoration with a tenfold budget increase, no restoration treatments, and no livestock grazing. Under all the scenarios, cover of vegetation states with native perennial understory declined and was replaced by tree-invaded and weed-dominated states. The greatest differences among alternative management scenarios resulted from the use of fire as a tool to maintain native understory. Among restoration scenarios, only the scenario assuming a tenfold budget increase had a more desirable outcome than the current management scenario. Removal of livestock alone had little effect on vegetation resilience. Rather, active restoration was required. The predictive power of the model was limited by current understanding of Great Basin vegetation dynamics and data needs including statistically valid monitoring of restoration treatments, invasiveness and invasibility, and fire histories. The authors suggest that such computer models can be useful tools for systematic analysis of potential impacts in land use planning. However, for a modeling effort to be productive, the management situation must be conducive to open communication among land management agencies and partner entities, including nonprofit organizations.

Climate↗

[Immunohistochemical characterization of salivary gland tumors with tissue micro-arrays].

Systematic analysis of gene expression in salivary gland tumors is necessary to identify genes associated with specific tumor types. From the salivary gland register of the University Hospital Hamburg-Eppendorf sufficient samples of various tumors were available to generate Tissue Micro-Arrays (TMA). In light of the considerable heterogeneity of salivary gland tumors, this study was aimed at evaluating the suitability of TMA in salivary gland diagnostics and research. Epithelial antigens are not sufficient for a tumor-type-specific characterization. Myoepithelial markers are suitable for distinguishing biphasic tumor types from purely epithelial tumors. The detection of amylase in acinic cell carcinomas, and the detection of steroid hormone receptors in these and other malignant salivary gland tumors particularly in combination with the expression of transcription factors, oncogenes and proliferation associated antigens result in characteristic expression profiles. These may prove to be valuable for further investigations, especially on the molecular level.

Biomarkers, Tumor↗

Spinal cord tumors.

Spinal cord tumors are rare; however, every radiologist should be able to recognize and readily identify those lesions often found in younger patients or children [1, 2, 3, 4, 5, 6, 7, 8,9]. Early diagnosis plays an important role in the management of the lesions and interferes with the prognosis and final outcome of the patient [10]. Plain X-ray of the spine and CT are of limited diagnostic value in cases of intramedullary pathology. Magnetic resonance imaging should be performed as soon as possible and as the first technique whenever an intrinsic spinal cord lesion is clinically suspected. Systematic analysis of the MR images together with a basic knowledge of the most common spinal cord tumors encountered, including astrocytomas, ependymomas, and hemangioblastomas, should provide a correct diagnosis and lead to appropriate treatment subsequently.

Adult↗

Assessment of a systematic expression profiling approach in ENU-induced mouse mutant lines.

Comparative genomewide expression profiling is a powerful tool in the effort to annotate the mouse genome with biological function. The systematic analysis of RNA expression data of mouse lines from the Munich ENU mutagenesis screen might support the understanding of the molecular biology of such mutants and provide new insights into mammalian gene function. In a direct comparison of DNA microarray experiments of individual versus pooled RNA samples of organs from ENU-induced mouse mutants, we provide evidence that individual RNA samples may outperform pools in some aspects. Genes with high biological variability in their expression levels (noisy genes) are identified as false positives in pooled samples. Evidence suggests that highly stringent housing conditions and standardized procedures for the isolation of organs significantly reduce biological variability in gene expression profiling experiments. Data on wild-type individuals demonstrate the positive effect of controlling variables such as social status, food intake before organ sampling, and stress with regard to reproducibility of gene expression patterns. Analyses of several organs from various ENU-induced mutant lines in general show low numbers of differentially expressed genes. We demonstrate the feasibility to detect transcriptionally affected organs employing RNA expression profiling as a tool for molecular phenotyping.

Animals↗

The genetic origin of mouse annexin VIII.

Mouse annexin VIII cDNA was characterized by DNA sequencing of expressed sequence tag clones, molecular systematic analysis, and genetic linkage mapping to investigate its evolutionary origin. Its subfamily identity, divergence pattern, and nucleotide substitution rate were established by comparison with other annexin cDNA and deduced protein sequences. The known phylogenetic association of annexin VIII in an evolutionary clade with annexins XI, IV, V, and VIa identified these close homologs as potential progenitors or duplication products. Cladistic analysis confirmed the base position of annexin XI and its relationship to annexin IV as a direct duplication product. Although annexin VIII also derived from annexin XI, the evolutionary branching order, gene separation times, and mapping results indicated that it was probably a subsequent duplication product of annexin IV about 300 million years ago. Dates were calibrated against the assumed separation time of 75 Mya for rodents from other mammals, divergence rates were based on comparisons of all available annexin species, and relative rate tests implied individually stable gene clocks for most annexins. Linkage mapping of mouse Anx8 to the centromeric region of Chromosome (Chr) 14 placed it in a more distal homology group from previously mapped Anx7 and Anx11. Despite their synteny, the combined proximity and segregation of these three annexins diminished the likelihood that they were mutual gene duplication products.

Amino Acid Sequence↗

Lifestyle issues and genitourinary tumours.

A variety of lifestyle factors, including physical activity, artificial sweeteners, alcohol consumption and smoking, have been reported to contribute to the risk of developing urological malignancies. A great number of epidemiological studies suggest that sports and physical activity may have a preventive influence on genitourinary tumours, especially on the incidence of prostate cancer. Smoking appears to be the most relevant lifestyle factor significantly increasing both incidence and mortality from bladder cancer. Furthermore, there is evidence implicating an association between tobacco use and kidney cancer. In contrast, prostate and testicular cancers are unlikely to be linked to tobacco use. As far as alcohol is concerned, most studies indicate that neither amount nor type of alcohol seems to be clearly associated with a risk of developing urological malignancies. However, some more recent cohort studies suggest a moderately increased risk for prostate and bladder cancer for specific types of alcohol. On the other hand, there is evidence that moderate alcohol consumption may even protect women from developing renal cancer. Since the introduction of artificial sweeteners, reports of potential cancer risks have circulated periodically through the mass media. The wide distribution of these agents and the fact that mostly combinations of the different compounds are added to a broad variety of food, drinks, drugs, and hygiene products complicates a systematic analysis of their potential impact on the development of urological malignancies. Nevertheless, so far not a single study has convincingly demonstrated a statistically significant risk of bladder cancer due to the consumption of artificial sweeteners. This survey demonstrates that the individual assessment of lifestyle factors not only may identify groups with an increased risk for urological malignancies but also clearly displays a potential for tumour prevention.

Alcohol Drinking↗