[Even low-acuity patients prefer hospital-based emergency care : A survey of non-urgent patients in an emergency department with unique regional position]. / Der Notfall "geht" ins Krankenhaus : Eine Befragung von Patienten mit niedriger Dringlichkeit in einer Notfallaufnahme mit regionaler Alleinstellung.

BACKGROUND: Besides increasing numbers of cases in German emergency departments (ED), the spectrum of attending patients is also changing. Patients with acute illnesses tend to prefer EDs to ambulatory care as primary contact point. This study examines the motives for use and use behavior of low-urgent ED-patients. METHODS: Anonymous patient survey in the ED of Wolfsburg Hospital between 12/2015 and 03/2016 with descriptive analysis. All patients with low urgency (Manchester-Triage-System (MTS), levels blue and green) were eligible. RESULTS: 81.5% of respondents (729 evaluable out of 7000 questionnaires distributed) attended the ED between 8:00 a. m. and 5:00 p. m., 70.1 % of them were walk-in patients. The motive most frequently cited was that they would receive better care in the ED (48.3 %). Contrary to acuity assessment, 67.8 % of respondents considered themselves a medium to life-threatening emergency. As alternative option, 49.2 % would choose a nearby clinic in the region for their complaints. CONCLUSION: Self-assessed urgency differs with acuity assessment according to MTS. Patients who fear an acute threat to their health do not use services provided in the ambulatory sector such as the emergency practice of the Association of Statutory Health Insurance Physicians in the immediate proximity sufficiently. Previous approaches for patient navigation do not seem to be successful in this setting. Strengthening of EDs as a single 24/7 access point for emergency care with simultaneous abolition of parallel care structures should be discussed.

[Questionnaire for the utilization of the Emergency Department : Implications for the patient survey]. / Fragebogen zur Inanspruchnahme der Notaufnahmen : Implikationen für die Patientenbefragung.

BACKGROUND: For several years, Emergency Departments (ED) in Germany have observed increasing patient numbers, resulting in ED crowding. This leads to the question of whether patients with nonurgent conditions could also receive adequate treatment in primary care. Our objective was to develop a quantitative questionnaire to investigate in a larger patient group the reasons for this and to describe the implications for a patient survey in the ED. METHODS: The development of the questionnaire was based on a literature search and the results of the qualitative EPICS-2 study. Two pretest surveys were conducted in three EDs at the Charité - Universitätsmedizin Berlin. We included patients aged ≥ 18 years with outpatient treatment and the categories blue (nonurgent), green (standard), or yellow (urgent) according to the Manchester Triage System (MTS). RESULTS: In total, 189 patients were recruited in two surveys (pretest 1: n = 89, pretest 2 n = 100). The final questionnaire includes 24 items, which were evaluated and adapted during both pretests. The items evaluate basic clinical characteristics, reasons for choosing the ED, prior contacts in primary care, utilization of primary care after-hours services as well as sociodemographic characteristics. Data from the hospital information system were used to link the survey data with clinical characteristics. CONCLUSIONS: The questionnaire is based on reasons for ED utilization. We recommend the written, self-applied questionnaire for patient surveys with plausibility checks conducted by staff. It is necessary to consider the heterogenic study surroundings in the ED, which requires a lot of flexibility during data collection.

[Standardized collection of presenting complaints in the emergency room : Integration of coded presenting complaints into the electronic medical record system of an emergency department and their value for health care research]. / Standardisierte Erhebung von Vorstellungsgründen in der Notaufnahme : Implementierung von codierten Vorstellungsgründen in das elektronische Notaufnahmeinformationssystem eines Schwerpunktversorgers und deren Potenzial für die Versorgungsforschung.

BACKGROUND: The point of entry of a patient in emergency care is a symptom or a complaint. To evaluate subsequent processes in an emergency department until a diagnosis is made, this information has to be taken into account. OBJECTIVES: We report the introduction of coded presenting complaints into the electronic medical record system of an emergency department and describe the patients based on these data. METHODS: The CEDIS presenting complaint list was integrated into the emergency department information system of an emergency department (38,000 patients/year). After 8 months, we performed an exploratory analysis of the most common presenting complaints. Furthermore, we identified the most frequent diagnoses for presenting complaint "shortness of breath" and the most frequent presenting complaints for the diagnosis of sepsis. RESULTS: After implementing the presenting complaint list, a presenting complaint code was assigned to each patient. In our sample (26,330 cases), "extremity pain and injury" comprised the largest group of patients (29.5%). "Chest pain-cardiac features" (3.7%) and "extremity weakness/symptoms of cerebrovascular accident" (2.4%) were the main cardiac and neurologic complaints, respectively. They were mostly triaged as urgent (>80%) and hospitalized in critical care units (>50%). The main diagnosis for presenting complaint "shortness of breath" was heart failure (25.1%), while the main presenting complaint for the diagnosis sepsis was "shortness of breath" (18.1%). CONCLUSIONS: Containing 171 presenting complaints, this classification was implemented successfully without providing extensive staff training. The documentation of coded presenting complaints enables symptom-based analysis of the health care provided in emergency departments.

In vivo measurement of the 3D kinematics of the temporomandibular joint using miniaturized electromagnetic trackers: technical report.

OBJECTIVE: The aim of this study was to evaluate the use of miniaturized electromagnetic trackers (1 × 0.5 × 0.5 cm) fixed on teeth of the maxilla and mandible to analyse in vivo the 3D kinematics of the temporomandibular joint (TMJ). A third sensor was fixed to the forehead, and a fourth sensor was used as a stylus pointer to detect several anatomical landmarks in order to embed a local frame on the cranium. Temporomandibular opening/closing, chewing, laterotrusion and protrusion were examined. RESULTS: The prime objective within this study was to rigidly attach electromagnetic minisensors on teeth. The key for a successful affixation was the kevlar interface. The distances between the two mandibular affixed sensors and between the two maxillar affixed sensors were overall smaller than 0.033 cm for position and 0.2° for attitude throughout the temporomandibular motions. The relative motions between a forehead sensor and the maxilla affixed sensor are too big to suggest a forehead sensor as an alternative for a maxilla affixed sensor. CONCLUSION: The technique using miniaturized electromagnetic trackers furthers on the methods using electromagnetic trackers on external appliances. The method allows full range of motion of the TMJ and does not disturb normal TMJ function.

Consideration of anisotropic elasticity minimizes volumetric rather than shear deformation in human mandible.

This article is focused on the role of anisotropic elasticity in the simulation of the load distribution in a human mandible, due to a lateral bite on the leftmost premolar. Based on experimental evidence, orthotropy of the elastic properties of the bone tissue has been adopted. The trajectories of anisotropic elasticity are reconstructed from (i) the organ's geometry and (ii) from coherent structures which can be recognized from the spatial distribution of the grey values coming from computer tomography (CT). A sensitivity analysis comprising various three-dimensional (3D) finite element (FE) simulations reveals the relevance of elastic anisotropy for the load carrying behavior of a human mandible: comparison of the load distributions in isotropic and anisotropic simulations indicates that anisotropy seems to "spare" the mandible from loading. Moreover, a maximum degree of anisotropy leads to kind of load minimization of the mandible, expressed by a minimum of different norms of local volumetric strain, evaluated throughout the organ. The observed optimization with respect to volumetric rather than shear strain seems to confirm the frequently emphazised role of volumetric-strain-induced fluid flow for the stimulation of cellular activity.

beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.

beta-Catenin is an essential molecule in Wnt/wingless signaling, which controls decisive steps in embryogenesis. To study the role of beta-catenin in skin development, we introduced a conditional mutation of the gene in the epidermis and hair follicles using Cre/loxP technology. When beta-catenin is mutated during embryogenesis, formation of placodes that generate hair follicles is blocked. We show that beta-catenin is required genetically downstream of tabby/downless and upstream of bmp and shh in placode formation. If beta-catenin is deleted after hair follicles have formed, hair is completely lost after the first hair cycle. Further analysis demonstrates that beta-catenin is essential for fate decisions of skin stem cells: in the absence of beta-catenin, stem cells fail to differentiate into follicular keratinocytes, but instead adopt an epidermal fate.

Cytochrome P450-dependent renal arachidonic acid metabolism in desoxycorticosterone acetate-salt hypertensive mice.

Cytochrome P450 (P450)-dependent arachidonic acid metabolites may act as mediators in the regulation of vascular tone and renal function. We studied arachidonic acid hydroxylase activities in renal microsomes from normotensive NMRI mice, desoxycorticosterone acetate (DOCA)-salt hypertensive mice, and DOCA-salt mice treated with either lovastatin or bezafibrate, both of which improve hemodynamics in this model. Control renal microsomes had arachidonic acid hydroxylase activities of 175+/-12 pmol. min(-1). mg(-1). The metabolites formed were 20- and 19-hydroxyarachidonic acid, representing approximately 80% and approximately 20% of the total hydroxylation. Treatment with DOCA-salt resulted in significantly decreased hydroxylase activities (to 84+/-4 pmol. min(-1). mg(-1)) of the total microsomal P450 content and a decrease in immunodetectable Cyp4a proteins. Lovastatin had no effect on these variables, whereas bezafibrate increased arachidonic acid hydroxylase activities to 163+/-12 pmol. min(-1). mg(-1). In situ hybridization with probes for Cyp4a-10, 12, and 14 revealed that Cyp4a-14 was the P450 isoform most strongly induced by bezafibrate. The expression was concentrated in the cortical medullary junction and was localized predominantly in the proximal tubules. In conclusion, these results suggest that the capacity to produce 20-hydroxyarachidonic acid is impaired in the kidneys of DOCA-salt hypertensive mice. Furthermore, bezafibrate may ameliorate hemodynamics in this model by restoring P450-dependent arachidonic acid hydroxylase activities. Lovastatin, on the other hand, exerts its effects via P450-independent mechanisms.

Requirement for beta-catenin in anterior-posterior axis formation in mice.

The anterior-posterior axis of the mouse embryo is defined before formation of the primitive streak, and axis specification and subsequent anterior development involves signaling from both embryonic ectoderm and visceral endoderm. Tauhe Wnt signaling pathway is essential for various developmental processes, but a role in anterior-posterior axis formation in the mouse has not been previously established. Beta-catenin is a central player in the Wnt pathway and in cadherin-mediated cell adhesion. We generated beta-catenin-deficient mouse embryos and observed a defect in anterior-posterior axis formation at embryonic day 5.5, as visualized by the absence of Hex and Hesx1 and the mislocation of cerberus-like and Lim1 expression. Subsequently, no mesoderm and head structures are generated. Intercellular adhesion is maintained since plakoglobin substitutes for beta-catenin. Our data demonstrate that beta-catenin function is essential in anterior-posterior axis formation in the mouse, and experiments with chimeric embryos show that this function is required in the embryonic ectoderm.

Impact of nonlinear heat transfer on temperature control in regional hyperthermia.

We describe an optimization process specially designed for regional hyperthermia of deep-seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Using linearly implicit methods in time and adaptive multilevel finite elements in space, we are able to integrate efficiently the instationary nonlinear heat equation with high accuracy. Optimal heating is obtained by minimizing an integral objective function which measures the distance between desired and model predicted temperatures. A sequence of minima is calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. We compare temperature distributions for two individual patients calculated on coarse and fine spatial grids and present numerical results of optimizations for a Sigma 60 Applicator of the BSD 2000 Hyperthermia System.

Polycation-mediated transfection: how to overcome undesirable side effects of sticky DNA complexes.

Using polycationic transfection one encounters undesired persistent binding to cells of sticky polycation/DNA complexes. These complexes simulate transfection under conditions where no uptake is expected e.g. at 4 degrees C if the uptake is by endocytosis. To overcome this problem, using H1/DNA complexes, we developed an easy and nontoxic method for removing the sticky complexes not taken up during the transfection phase. The cells are simply washed with isotonic (0.1 M) MgCl2 solution, which enables the complete removal of the complexes by their rapid dissolution.

Modified Kidner procedure utilizing a Mitek bone anchor.

The recent development of small bone suture anchors has created several potential applications in reconstructive surgery of the foot. Mitek bone anchors are simple to insert, require less aggressive dissection and surgical time than reefing of the redundant posterior tibial tendon, and are a reliable method of tendon-to-bone fixation. Mitek bone anchors are an excellent technique for the treatment of redundant tibialis posterior tendon following a modified Kidner procedure. In modified Kidner procedures involving an excessively large os tibiale externum, Mitek anchoring of the redundant tibialis posterior tendon to the navicular bone is an excellent means for secure plication of the posterior tibial tendon in cases involving intraoperative tendon laxity. A description of the Mitek Anchor System and technique of application in a modified Kinder procedure is presented. The purpose of this study was to describe patient satisfaction and long-term clinical outcomes of the modified Kinder procedure with and without the Mitek bone anchoring system. A retrospective study of the modified Kinder procedure was performed with 13 patients being evaluated, seven with Mitek anchoring and six without. The University of Maryland 100-point Painful Foot Center Scoring System was modified to be more specific to the modified Kinder procedure for assessment of subjective long-term results. Patient overall satisfaction was rated good to excellent by 85.6% of patients in the Mitek group and by 100% of patients in the non-Mitek group. Use of the Mitek anchor allowed for quicker postoperative recovery to resumption of ambulation without assistive devices (average of 3 weeks vs. 4.42 weeks) and a quicker return to pain-free ambulation in normal shoegear (average of 4 weeks vs. 6 weeks). Mitek anchoring of the tibialis posterior tendon, theoretically, increases medial arch support as evidenced by 14% of the Mitek group and 67% of the non-Mitek group requiring postoperative orthotics.

The spread and uptake pattern of intracerebrally administered oligonucleotides in nerve and glial cell populations of the rat brain.

The fate of 15-mer phosphorothioate-modified antisense oligonucleotides to c-fos was followed after their microinjection into rat brain. Using radiolabeled oligonucleotides, it was demonstrated that the bulk of the material stays in the injected region but that a minor part is transported with the projection pathways to regions far away from the site of injection. Using tetramethylrhodamine-isothiocyanate (TRITC) labeling as well as fluorescein isothiocyanate (FITC) labeling, it was found that the oligonucleotides were taken up by a great number of cells within 30 minutes after the injection. A diffuse cytoplasmic staining and also nuclear staining were observed in these cells, which could be identified exclusively as neurons by double labeling for the neuron-specific protein NeuN. At later times (6, 24, and 48 hours), the appearance of the oligonucleotides changed gradually to a punctate cytoplasmic staining, which by electron microscopic analysis was shown to be caused by the presence of the oligonucleotides in intracellular vesicles. The pattern of intracellular fluorescence was changed when the oligonucleotides were injected together with the cationic lipid 1,2-bis(oleoyloxy)-3-(trimethylammonio)propane (DOTAP). A small number of astrocytes and microglial cells were found to be labeled by the oligonucleotides, but only at later times after the injection and exclusively in a punctate cytoplasmic manner. Thus, the uptake of oligonucleotides in the nerve and glial cell populations of the brain might involve different mechanisms, the one in the neurons appearing to be very rapid and potent.

Optimization of temperature distributions for regional hyperthermia based on a nonlinear heat transfer model.

We describe an optimization process specially designed for regional hyperthermia of deep seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat-transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Optimal heating is obtained by minimizing an integral object function which measures the distance between desired and model predicted temperatures. Sequential minima are calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. Numerical results for a Sigma 60 applicator are presented.

From totipotent embryonic stem cells to spontaneously contracting smooth muscle cells: a retinoic acid and db-cAMP in vitro differentiation model.

Vascular smooth muscle cell (VSMC) differentiation is important in understanding vascular disease; however, no in vitro model is available. Totipotent mouse embryonic stem (ES) cells were used to establish such a model. To test whether the ES cell-derived smooth muscle cells expressed VSMC-specific properties, the differentiated cells were characterized by 1) morphological analysis, 2) gene expression, 3) immunostaining for VSMC-specific proteins, 4) expression of characteristic VSMC ion channels, and 5) formation of [Ca2+]i transients in response to VSMC-specific agonists. Treatment of embryonic stem cell-derived embryoid bodies with retinoic acid and dibutyryl-cyclic adenosine monophosphate (db-cAMP) induced differentiation of spontaneously contracting cell clusters in 67% of embryoid bodies compared with 10% of untreated controls. The highest differentiation rate was observed when retinoic acid and db-cAMP were applied to the embryoid bodies between days 7 and 11 in combination with frequent changes of culture medium. Other protocols with retinoic acid and db-cAMP, as well as single or combined treatment with VEGF, ECGF, bFGF, aFGF, fibronectin, matrigel, or hypoxia did not influence the differentiation rate. Single-cell RT-PCR and sequencing of the PCR products identified myosin heavy chain (MHC) splice variants distinguishing between gut and VSMC isoforms. RT-PCR with VSMC-specific MHC primers and immunostaining confirmed the presence of VSMC transcripts and MHC protein. Furthermore, VSMC expressing MHC had typical ion channels and responded to specific agonists with an increased [Ca2+]i. Here we present a retinoic acid + db-cAMP-inducible embryonic stem cell model of in vitro vasculogenesis. ES cell-derived cells expressing VSMC-specific MHC and functional VSMC properties may be a suitable system to study mechanisms of VSMC differentiation.

Subcellular localization of angiotensin II immunoreactivity in the rat cerebellar cortex.

We localized angiotensin II (Ang II) immunoreactivity in the rat cerebellar cortex with immunogold staining methods. Perfusion fixation with high amounts of glutaraldehyde and the use of cryoultramicrotomy caused remarkable changes in immunostaining versus formaldehyde/picric acid fixation. With the use of monoclonal and polyclonal anti-Ang II, Ang II immunoreactivity was prominent in cerebellar neurons such as Purkinje, granule, basket, and stellate cells. At the subcellular level, the peptide was clearly localized in nuclei, and in some cell types, such as endothelial and granule cells, it was nearly exclusively present in the transcriptionally active euchromatin. Intracellular Ang II immunoreactivity was also detected in vesicle-like structures in cytoplasm and mitochondria and at cell-cell contacts. Additional experiments with liver and adrenal tissue confirmed the nuclear localization of Ang II immunoreactivity, suggesting a role of Ang II in the regulation of gene transcription.

Effects of intracellular angiotensin II in vascular smooth muscle cells.

Angiotensin (Ang) II is present inside vascular smooth muscle cells (VSMCs); however, its intracellular functions, if any, are unknown. We tested the hypothesis that intracellular Ang II exerts effects on cytosolic Ca2+ ([Ca2+]i) in VSMCs. Ang II was administered via microinjection. Intracellular Ang II localization was demonstrated by fluorescein-labeled Ang II and electron microscopy. [Ca2+]i was monitored by confocal microscopy with fluo 3. Ang II was identified in endosomes and in the nucleus by both localizing techniques. Microinjection of Ang II (10(-10) mol/L) led to a rapid increase in [Ca2+]i in the cytosol and in the nucleus. The [Ca2+]i increase was due to the influx of extracellular Ca2+ ions. The intracellular Ang II effect was totally inhibited by the concomitant injection of the Ang II antagonist CV-11947. Desensitization of extracellular Ang II receptors, on the other hand, did not influence the intracellular effects, nor did extracellular CV-11947. The increase in [Ca2+]i was observed not only in the microinjected cell but also in directly adjacent VSMCs. In contrast to the microinjected cells, the [Ca2+]i increase in the adjacent cells was mostly due to release from intracellular stores. Pretreatment with thapsigargin abolished the Ang II response in adjacent cells. Microinjection of inositol tris-phosphate induced a [Ca2+]i response in adjacent cells that was similar to the Ang II-induced effects. Preincubation of VSMCs with the uncoupling substances dimethyl sulfoxide and heptanol did not decrease the Ang II response but instead prevented a [Ca2+]i surge in adjacent cells. We conclude that intracellular Ang II binds to intracellular Ang II receptors and elicits an increased [Ca2+]i in the injected cell and, thereafter, cells in the immediate neighborhood. Cell-cell contact is necessary for the Ang II-mediated effects. The data suggest that intracellular Ang II may stimulate a cluster of VSMCs from a single cell via the release of second messengers.

Expression of cytochrome P45011B1 mRNA in the brain of normal and hypertensive transgenic rats.

Cytochrome P45011B1 (11 beta-hydroxylase) was detected in the brain of male rats by in situ hybridization methods. Normal Sprague-Dawley rats were compared to the transgenic strain TGR(mRen2)27, characterized by the expression of the murine Ren-2d renin gene and the development of severe hypertension. Specific riboprobes were generated by in the vitro transcription of a 152 base-pair long cDNA template 35S-labeled riboprobes were hybridized to cryostat sections from adrenal glands and from two different levels of the brain using standard protocols and varying washing conditions. After exposure of the radiolabeled sections to X-ray film, the signals were quantified and compared. Following autoradiography and counterstaining, cytochrome P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis of the adrenal cortex and in distinct layers of the cerebral cortex. High signal densities were obtained in the layers II-IV of the neocortex and in the layer II of the piriform cortex, although the concentrations of cytochrome P45011B1 mRNA were remarkably lower in the central nervous system as compared to adrenal glands. As revealed by the semi-quantitative analysis, there was a slight increase in adrenal 11 beta-hydroxylase mRNA in the transgenic rats, whereas the brain seems to express nearly the same amount of this enzyme in both strains. The cytochrome P45011B1 mRNA expression in distinct cells, probably nerve cells, and especially in regions with high densities of glucocorticoid receptors points to a possible function of brain derived corticosterone in receptor activation.

Adenocarcinoma of the lung with metatarsal metastasis.

Foot pain is a most unusual presentation of metastatic malignancy. Metastases to the hands or feet (acrometastases) have been recognized in only a few cases. A 68-year-old male, with a history of chronic gout, presented with left foot pain for 3 months duration. After conservative treatment failed to relieve his pain, radiographic and eventual bone biopsy of a cystic lesion involving the first metatarsal head revealed a Grade IV adenocarcinoma.