Atopy patch testing with aeroallergens in a large clinical population of dermatitis patients in Germany and Switzerland, 2000-2015: a retrospective multicentre study.

BACKGROUND: The diagnostic significance of the atopy patch test for the management of dermatitis possibly triggered by aeroallergens is still controversial. However, sufficiently large studies with routinely tested standardized aeroallergen patch test preparations in dermatitis patients are lacking. OBJECTIVE: To evaluate the reaction frequency and the reaction profiles of 10 until mid-2015 commercially available, standardized aeroallergen patch test preparations of the 'Stallerpatch' test series (Stallergenes, Antony Cedex, France) in a large multicentre patient cohort. METHODS: A retrospective data analysis of patients with suspected aeroallergen-dependent eczematous skin lesions was performed, who were patch tested in 15 Information Network of Departments of Dermatology-associated clinics between 2000 and 2015. Patients were stratified according to their atopic dermatitis (AD) status. RESULTS: The study group included 3676 patients (median age 41 years, 34.8% males, 54.5% AD). The most common aeroallergens causing positive patch test reactions were Dermatophagoides pteronyssinus (19.6%), Dermatophagoides farinae (16.9%), birch (6.2%), timothy grass (6.0%), cat dander (5.4%), mugwort (4.9%) and dog dander (4.6%). Reactions to other pollen allergen preparations, that is 5 grasses (3.2%), cocksfoot (2.1%) and plantain (1.6%), were less common. Positive patch test reactions to aeroallergens were consistently more frequent in patients with AD. These patients showed proportionally less dubious, follicular, irritant and weak positive reactions. Independent of AD status, a patient history of past or present allergic rhinitis was associated with an increased chance of a positive aeroallergen patch test reaction to pollen allergens. CONCLUSION: The aeroallergen patch test is a useful add-on tool in clinical routine, especially in patients with AD and/or respiratory allergy. A patch test series comprising Dermatophagoides pteronyssinus, Dermatophagoides farinae, birch, timothy grass, cat dander and mugwort seems to be suitable. Controlled studies with specific provocation and elimination procedures are required to further evaluate the diagnostic significance of the proposed screening series.

[Effect of humor training on stress, cheerfulness and depression in patients with coronary artery disease and refractory angina pectoris]. / Effekt von Humortraining auf Stress, Heiterkeit und Depression bei Patienten mit koronarer Herzkrankheit und therapierefraktärer Angina pectoris.

BACKGROUND: Angina pectoris refractory to conventional medical treatment is a common phenomenon in patients with stable coronary artery disease (CAD). Many of these patients suffer from depression and generate substantial costs in the healthcare system. Therefore, the development of new therapeutic concepts is of particular importance. This study investigated whether professional, structured humor training has a positive effect on the symptoms of patients with treatment refractory angina pectoris. METHODS: Between 2013 and 2014 a total of 35 patients with stable CAD were included. Enrolment was possible if patients suffered from treatment refractory angina pectoris (Canadian Cardiovascular Society, CCS grades II-IV) despite optimal antianginal medication and exhaustion of options for myocardial revascularization. Previously, 25.8% of the patients had had a myocardial infarction. In this study, a professional humor coaching was conducted with a duration of 7 weeks. In order to evaluate the effects of the coaching, the following examinations were performed before and after the intervention: exercise stress test (treadmill), hair segment cortisol analysis, Beck Depression Inventory (BDI), the Trier Inventory for the Assessment of Chronic Stress (TICS) and the State-Trait-Cheerfulness Inventory (STCI). RESULTS: Out of the 35 initially recruited patients 31 completed the study. The mean age was 65.5 years and 94.5% were female. There was a significant improvement in cheerfulness (STCI, pre 23.3 ± 5.4, post 27.5 ± 5, p = 0,03). This effect was even stronger in a subgroup analysis in which only female patients were included (pre 23.6 ± 5.5, post 27.7 ± 4.6, p = 0.003). The results of the BDI showed a remarkable improvement in the pre-post analysis (pre 14.6 ± 8.1, post 11.0 ± 6.5, p = 0.064). Analyzing only the female patients, this difference became significant (pre 13.1 ± 6.4, post 9.9 ± 4.6 p = 0,037). The hair segment investigations showed that patients who had a higher cortisol level in the beginning (>25. percentile, n = 22) showed a significant reduction of the cortisol concentration (pre 6.54 pg/mg, 3.78-12.12 pg/mg, post 3.65 pg/mg, 2.82-7.68 pg/mg, p = 0.029). CONCLUSION: Patients with refractory angina pectoris and stable CAD benefit from a professional humor coaching. This effect was shown in a) a significant decrease in cortisol concentrations in the hair segment analysis, b) an improvement in cheerfulness in the STCI and c) a significant difference in the BDI between pre-post values.

Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state.

Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABAA receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic doses of ketamine. Thus GABAergic deficits may causally contribute to depressive disorders, while antidepressant therapies may enhance GABAergic synaptic transmission. Here we tested the hypothesis that sustained enhancement of GABAergic transmission alone is sufficient to elicit antidepressant-like behavior, using disinhibition of GABAergic interneurons. We focused on somatostatin-positive (SST+) GABAergic interneurons because of evidence that their function is compromised in MDD. To disinhibit SST+ interneurons, we inactivated the γ2 subunit gene of GABAA receptors selectively in these neurons (SSTCre:γ2f/f mice). Loss of inhibitory synaptic input resulted in increased excitability of SST+ interneurons. In turn, pyramidal cell targets of SST+ neurons showed an increased frequency of spontaneous inhibitory postsynaptic currents. The behavior of SSTCre:γ2f/f mice mimicked the effects of anxiolytic and antidepressant drugs in a number of behavioral tests, without affecting performance in a spatial learning- and memory-dependent task. Finally, brain extracts of SSTCre:γ2f/f mice showed decreased phosphorylation of the eukaryotic elongation factor eEF2, reminiscent of the effects of ketamine. Importantly, these effects occurred without altered activity of the mammalian target of rapamycin pathway nor did they involve altered expression of SST. However, they were associated with reduced Ca2+/calmodulin-dependent auto-phosphorylation of eEF2 kinase, which controls the activity of eEF2 as its single target. Thus enhancing GABAergic inhibitory synaptic inputs from SST+ interneurons to pyramidal cells and corresponding chronic reductions in the synaptic excitation:inhibition ratio represents a novel strategy for antidepressant therapies that reproduces behavioral and biochemical end points of rapidly acting antidepressants.

[Adequate anti-infective treatment : Importance of individual dosing and application]. / Adäquate Antiinfektivatherapie : Bedeutung der individuellen Dosierung und Applikation.

Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (Vd) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beta-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.

[Between psyche and brain : State of the art in psychiatry]. / Zwischen Psyche und Gehirn : Zur Standortbestimmung der Psychiatrie.

Since its development around 1800 psychiatry has been oscillating between the poles of the sciences and the humanities, being directed towards subjective experience on the one hand and towards the neural substrate on the other hand. Today, this dualism seems to have been overcome by a naturalism, which identifies subjective experience with neural processes, according to Griesinger's frequently quoted statement "mental diseases are brain diseases". The progress achieved by the neurobiological paradigm on the level of a fundamental science is in contrast to the tendency to isolate mental illnesses from the patients' social relationships and to neglect subjectivity and intersubjectivity in their explanation. What should be searched for is therefore an overarching paradigm that is able to establish psychiatry as a relational medicine in an encompassing sense: as a science and practice of biological, psychological and social relationships and their disorders. Within such a paradigm, the brain may be understood and investigated as the central "relational organ" without reductionist constrictions.

[Disorders of the will in psychopathology]. / Willensstörungen in der Psychopathologie.

At the beginning of modern psychopathology the notion of the will had a high significance. Thus, the works of Eugen Bleuler, Emil Krapelin and Karl Jaspers show an intensive study of disorders of the will, such as abulia, ambivalence or disorders of impulse control. Retrospectively, changes of the scientific paradigms in psychology could be one of the reasons for a break, which led to giving up the concept of the will in psychopathology. With increasing interest in issues of agency and free will, however, a reactivation of this central concept could close a gap in psychopathology as well as in therapeutic practice. Methodologically, a psychopathology of the will may be founded on a differential typological phenomenology. To this purpose, the article first proposes a classification along the structural components of conation, suspension and volition, then gives a temporal analysis of the predecisional, the decisional and the postdecisional phases. The aim of the article is to help identify different disorders of the will, thus also furthering a psychotherapy of will, which can be connected with both cognitive behavioral and psychodynamic approaches.

Factor XII: a novel target for safe prevention of thrombosis and inflammation.

Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein-kinin system and the intrinsic pathway of coagulation. When zymogen FXII comes into contact with negatively charged surfaces, it auto-activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa-blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti-inflammatory properties.

[Implant augmentation in pelvic surgery. Options and technique]. / Implantataugmentation am Becken. Optionen und Technik.

BACKGROUND: Osteoporotic fractures of the pelvis are an increasing problem in trauma surgery. Sufficient implant anchorage is reduced due to the poor bone stock; however, early mobilization is especially necessary for geriatric patients in order to prevent additional complications. MATERIAL AND METHODS: Implant augmentation may be one technique to increase implant anchorage and stability in osteoporotic bone. This procedure is currently used in the treatment of osteoporotic fractures of the dorsal pelvic ring. Beside the augmentation of iliosacral screws in the treatment of sacral insufficiency fractures, cement augmentation with lumbar or sacral pedicle screws is used for increased stability. INDICATIONS AND RISKS: Implant augmentation in pelvic surgery should be indicated crucially due to the specific risks of the procedure. Cement leakage and heat generation during cement curing (when PMMA--polymethylmetacrylate--cement is used) can compromise neurovascular structures. Potential complications like cement embolism are possible. CONCLUSION: The use of special implants (cannulated and perforated screws) as well as intraoperative navigation and 3D imaging increase patient safety and help to make implant augmentation a low risk procedure.

[Psychopathology and film: a valuable interaction?]. / Psychopathologie en film: een waardevolle interactie?

BACKGROUND: Film or film fragments are often used in psychopathology education. However, so far there have been very few articles that have discussed the benefits and limitations of using films to explain or illustrate psychopathology. Although numerous films involves psychopathology in varying degrees, it is not clear how we can use films for psychopathology education. AIM: To examine the advantages, limitations and possible methods of using film as a means of increasing our knowledge and understanding of psychiatric illnesses. METHOD: We discuss five examples that illustrate the interaction of film and psychopathology. On the one hand we explain how the psychopathological concepts are used in each film and on the other hand we explain which aspects of each film are valuable aids for teaching psychopathology. RESULTS: The use of film makes it possible to introduce the following topics in psychopathological teaching programme: holistic psychiatric reasoning, phenomenology and the subjective experience, the recognition of psychopathological prototypes and the importance of context. CONCLUSION: There is undoubtedly an analogy between the method we have chosen for teaching psychopathology with the help of films and the holistic approach of the psychiatrist and his or her team. We believe psychopathology education can benefit from films and we would recommend our colleagues to use it in this way.

An exploratory evaluation of the utility of transcriptional and urinary kidney injury biomarkers for the prediction of aristolochic acid-induced renal injury in male rats.

The predictive value of different urinary and transcriptional biomarkers was evaluated in a proof-of-principle toxicology study in rats using aristolochic acid (AA), a known nephrotoxic agent. Male Wistar rats were orally dosed with 0.1, 1, or 10 mg/kg for 12 days. Urine was collected on days 1, 5, and 12 over 24 hours. Gene expression analysis was also conducted using quantitative real-time polymerase chain reaction and Illumina whole-genome chips. Protein biomarkers (Kim-1, Timp-1, vascular endothelial growth factor, osteopontin, clusterin, cystatin C, calbindin D-28K, ß2-microglobulin, α-glutathione S-transferase, GSTY1b, RPA-1, and neutrophil gelatinase-associated lipocalin) were measured in these urine samples. Treatment with AA resulted in a slight dose- and/or time-dependent increase in urinary ß2-microglobulin, lipocalin 2, and osteopontin before an increase in serum creatinine or serum urea nitrogen was observed. A strong decrease in urinary calbindin D-28K was also detected. The Compugen Ltd. prediction model scored both the 1- and 10-mg/kg AA dose groups as positive for nephrotoxicity despite the absence of renal histopathological changes. In addition, several previously described transcriptional biomarkers were identified as early predictors of renal toxicity as they were detected before morphological alterations had occurred. Altogether, these findings demonstrated the predictive values of renal biomarkers approved by the Food and Drug Administration, European Medicines Agency, and Pharmaceuticals & Medical Devices Agency in AA-induced renal injury in rats and confirmed the utility of renal transcriptional biomarkers for detecting progression of compound-induced renal injury in rats. In addition, several transcriptional biomarkers identified in this exploratory study could present early predictors of renal tubular epithelium injury in rats.

Ultrasonographic pattern of spontaneous resolving fetal ovarian cyst: a case report.

Fetal ovarian cyst is diagnosed at the rate of one per 2,500 live births and its behaviour in utero may range from spontaneous resolution with no further consequences to torsion, necrosis, and to the necessity of surgical treatment in the postnatal stage. Ovarian cyst torsion in a fetus results in the loss of its reproductive function in adult life. The authors present a case of spontaneous resolving fetal ovarian cyst. The lesion was diagnosed during an ultrasound scan in 30th week of pregnancy. An ultrasound scan performed two weeks later revealed symptoms of cyst torsion; the lesion was 5.7 cm in diameter, heterogeneous, and had a normoechogenic inside. A subsequent ultrasound exam showed a lesion with a diameter of 2.16 cm. An ultrasound exam of the newborn's abdominal cavity performed on the second day showed that the cyst was six mm in diameter. However, the cyst did not show on an ultrasound scan made on the fourth day.

Bet-hedging in stochastically switching environments.

We investigate the evolution of bet-hedging in a population that experiences a stochastically switching environment by means of adaptive dynamics. The aim is to extend known results to the situation at hand, and to deepen the understanding of the range of validity of these results. We find three different types of evolutionarily stable strategies (ESSs) depending on the frequency at which the environment changes: for a rapid change, a monomorphic phenotype adapted to the mean environment; for an intermediate range, a bimorphic bet-hedging phenotype; for slowly changing environments, a monomorphic phenotype adapted to the current environment. While the last result is only obtained by means of heuristic arguments and simulations, the first two results are based on the analysis of Lyapunov exponents for stochastically switching systems.

Local delivery of growth factors using coated suture material.

The optimization of healing processes in a wide range of tissues represents a central point for surgical research. One approach is to stimulate healing processes with growth factors. These substances have a short half-life and therefore it seems useful to administer these substances locally rather than systemically. One possible method of local delivery is to incorporate growth factors into a bioabsorbable poly (D, L-lactide) suspension (PDLLA) and coat suture material. The aim of the present study was to establish a procedure for the local delivery of growth factors using coated suture material. Sutures coated with growth factors were tested in an animal model. Anastomoses of the colon were created in a rat model using monofilament sutures. These were either untreated or coated with PDLLA coating alone or coated with PDLLA incorporating insulin-like growth factor-I (IGF-I). The anastomoses were subjected to biomechanical, histological, and immunohistochemical examination. After 3 days the treated groups showed a significantly greater capacity to withstand biomechanical stress than the control groups. This finding was supported by the results of the histomorphometric. The results of the study indicate that it is possible to deliver bioactive growth factors locally using PDLLA coated suture material. Healing processes can thus be stimulated locally without subjecting the whole organism to potentially damaging high systemic doses.

Establishment of a reliable in-vivo model of implant-associated infection to investigate innovative treatment options.

The increasing number of implant-associated infections and of multiresistant pathogens is a major problem in the daily routine. In the field of osteomyelitis, it is difficult to manage a valid clinical study because of multiple influencing factors. Therefore, models of osteomyelitis with a simulation of the pathophysiology to evaluate treatment options for implant-associated infections are necessary. The aim of this study is to develop a standardized and reproducible osteomyelitis model in-vivo to improve treatment options. This study analyses the influence of a post-infectious implant exchange one week after infection and the infection progress afterward in combination with a systemic versus a local antibiotic treatment in-vivo. Therefore, the implant exchange, the exchange to a local drug-delivery system with gentamicin, and the implant removal are examined. Furthermore, the influence of an additional systemic antibiotic therapy is evaluated. An in-vivo model concerning the implant exchange is established that analyzes clinic, radiologic, microbiologic, histologic, and immunohistochemical diagnostics to obtain detailed evaluation and clinical reproducibility. Our study shows a clear advantage of the combined local and systemic antibiotic treatment in contrast to the implant removal and to a non-combined antibiotic therapy. Group genta/syst. showed the lowest infection rate with a percentage of 62.5% concerning microbiologic analysis, which is in accordance with the immunohistochemical, cytochemical, histologic, and radiologic analysis. Our in-vivo rat model has shown valid and reproducible results, which will lead to further investigations regarding treatment options and influencing factors concerning the therapy of osteomyelitis and implant-associated infections.

[Treatment of disseminated granuloma annulare with anthralin]. / Therapie des Granuloma anulare disseminatum mit Anthralin.

Granuloma annulare is a benign, often asymptomatic and self-limiting granulomatous skin disease. In cases of disseminated granuloma annulare, spontaneous regression is considerably less frequent than in localized forms so that therapy is often desired. Systemic treatments should always be assessed critically and reserved for patients who are severely affected and in whom treatment approaches with few side effects such as local application of anthralin do not suffice to achieve a satisfactory effect.

[Periprosthetic fractures. An interdisciplinary challenge]. / Periprothetische Frakturen. Eine interdisziplinäre Herausforderung.

Demographic changes and rising numbers of implanted prostheses accompanied by increasing demands on mobility and activities of the elderly will lead to an increasing number of periprosthetic fractures in the future. Poor bone quality, geriatric comorbidities and multiple prostheses result in an increased risk for this type of fracture in the old patient. Management of these patients is challenging and demanding and needs an interdisciplinary approach. The present work describes the different aspects of periprosthetic fractures in the geriatric patient with regard to epidemiology, risk factors, prevention and treatment options.

[Pelvic ring fractures in the elderly. Underestimated osteoporotic fracture]. / Beckenringfrakturen im Alter. Die unterschätzte osteoporotische Fraktur.

The incidence of pelvic fractures at 0.3-8% is low compared to all fractures. Nevertheless, the number of pelvic fractures in the elderly is increasing. Due to the increased age of the patient differences in trauma mechanism, fracture pattern and therapy occur. Most pelvic fractures in the elderly are caused by low-energy trauma. This makes it difficult to find the right diagnosis especially in insufficiency fracture of the pelvis. The time until the right treatment is started is prolonged significantly. Elderly patients who suffer from a high-energy fracture have a significantly higher risk of haemorrhage. At the same time emergency stabilisation of the pelvis using a C-clamp is dangerous due to the special fracture morphology with transiliac instabilities and the combination with osteoporosis. Low-energy trauma leads to simple fractures of the pubis, which often can be treated without operation. In these cases fractures of the dorsal pelvic ring need to be excluded using CT scan. Fracture of the dorsal part of the pelvic ring such as insufficiency fractures of the sacrum should be stabilized by 3D-guided percutaneous iliosacral screw fixation to reduce pain and allow early mobilisation.

[Skin tests for diagnostics of allergic immediate-type reactions. Guideline of the German Society for Allergology and Clinical Immunology]. / Hauttests zur Diagnostik von allergischen Soforttyp-Reaktionen. Leitlinie der Deutschen Gesellschaft für Allergologie und klinischen Immunologie (DGAKI).

Skin tests in patients with IgE-mediated immediate type allergy are performed with the intention to establish a contact between allergens and skin mast cells. The latter carry specific IgE antibodies on their surface. If mast cells get activated, mediators (mainly histamine) are released which induce a visible skin reaction (wheal and erythema).[nl]Skin tests are indicated, if an immediate type allergic disease is suspected. Systemic anaphylactic reactions at skin testing are very rare. However, it is necessary to take them into account and to provide emergency treatment. Relative contraindications comprise skin diseases in the test area, poor general condition and insufficiently treated severe asthma. If tests are used, which have a higher risk for a systemic anaphylactic reaction, pregnancy or beta-blocker therapy, are further contraindications.[nl]Skin test application does not depend on patient age. However, in pre-school age tests are reluctantly performed. It is essential to consider the half-life of drugs which may interfere with the test result, and which have to be discontinued early enough before testing. After anaphylactic reactions there may be a refractory period. Therefore, tests should not be done within the first week after such reactions. Skin prick tests are the procedures of first choice, intradermal tests are more sensitive than prick tests. Skin tests are performed at the flexor side of the forearm. As intradermal tests are more inconvenient, testing can be also done at a less susceptible site of the body (upper back).[nl]It is recommended to use standardized test extracts. However, if standardised extracts are not available or do not yield suitable test results, one may switch to other preparations. If the patient shows a positive reaction to a non-standardized substance, control tests should be performed in healthy subjects in order to exclude an unspecific reaction.[nl]The reaction is read after 15 to 20 min. Skin tests are regarded positive if the mean wheal diameter is ≥ 3 mm at the prick test, and ≥ 5 mm at the intradermal test.[nl]Skin test results may be negative although patients are allergic. If a skin test is positive, one will have to distinguish reactions, which are clinically relevant, from those, which are not. History and/or challenge tests help to clarify the relevance of a sensitization. Usually, a clinically irrelevant sensitization does not lead to practical consequences.