[A critical perspective on the global research activity in the field of bladder cancer]. / Eine kritische Betrachtung der globalen Forschungsaktivität zum Thema Harnblasenkrebs.

BACKGROUND: Bladder cancer (BC) is one of the most common forms of cancer world-wide. This underestimated disease can cause severe morbidity and mortality in individuals. Increasing awareness can be depicted by the increasing numbers of publications since the 1990s. Hence, it is challenging for a scientist to obtain an overview of the topic. To quantify the global research activity in this field, a scientometric investigation was conducted. MATERIAL AND METHODS: Using the database Web of Science, the bibliometric data of publications on the topic of BC was acquired for the period 1900-2007. According to the NewQIS protocol, different visualization techniques and scientometric methods were applied. RESULTS: A total of 19,651 publications were evaluated. The USA takes a leading position in terms of the overall number of publications, institutions, and collaborations. International collaboration on BC has changed considerably in terms of quantity during the past 20 years. The largest number of articles and the highest number of citations regarding BC are found in the Journal of Urology. Thus, it is considered the most prolific journal. Furthermore, the productivity (i. e., publication numbers) of authors and scientific impact (i. e., citation rates) vary greatly. CONCLUSION: The field of BC continues to progress, whereby the influence of international co-operation on scientific progress is of increasing importance. New evaluation factors/tools have to be established for a more reliable evaluation of scientific work.

[Working conditions of physicians in hospitals--A comparison of specialties in German hospitals (iCept-Study)]. / Ärztliche Arbeitsbedingungen im Krankenhaus--Ein Vergleich der Fachgebiete (iCept-Studie).

BACKGROUND: In the context of the iCept-Study several medical specialties have been examined for their stress related working conditions. This study contrasts the different medical specialties. METHODS: The iCept-Study was designed as a web based survey in which altogether 7.090 respondents took part. The published data concerning the iCept-Study was systematically analyzed focusing on distress and job satisfaction. RESULTS: 53,9% of respondents showed unfavorable working conditions with an ER/JDC-Ratio > 1 (distress). Especially surgical specialties showed a higher prevalence: The odds ratio of surgery to anesthesiology was at 1,59 (95%-CI: 1,35|1,86; p < 0,001). On the other hand specialties like occupational medicine showed a lower prevalence in comparison with the average: The odds ratio was here at 0,37 (95%CI: 0,19|0,71; p < 0,01). Furthermore 55,8% of respondents stated that they were very satisfied with their job. CONSEQUENCES: Surgical specialties encountered distress the most. Moreover there was a positive correlation between high job satisfaction and lack of distress evident. Therefore it seems that distress and job satisfaction are two dependent characteristics of a changing work environment. Especially surgical specialties need to catch up with today's demand of improved working conditions and thus reducing distress and increasing satisfaction.

[Arthrosis: a scientometric analysis]. / Arthrose : Eine szientometrische Analyse.

BACKGROUND: In industrialized nations, arthrosis is one of the most frequent causes of physical disability and impaired quality of life in older people. OBJECTIVES: There are still no direct and curative therapies. In addition, the causative mechanisms of this disease have not been sufficiently deciphered and investigated so far. MATERIALS AND METHODS: For the present article, publications from 1900-2013 in the ISI Web of Science were reviewed. Quantitative and qualitative aspects are taken into account and are examined based on scientometric analysis methods. The illustrations demonstrate the global structure of the research and citation activity by Density Equalizing Map Projection. In addition, the radar charts illustrate the bi- and multilateral research and institutional cooperation. RESULTS: On the basis of the search criteria, a total of 46,212 publications were identified. Approximately 95 % of the publications date back to the last 25 years. In addition to the number of publications, the number of citations has increased continuously. The analysis of the country collaborations as well as the number of institutions indicates a predominance of the United States. Most articles about arthrosis concern the subject areas of rheumatology, orthopedics, and surgery. CONCLUSION: This study provides the first comprehensive, scientometric findings and illustrates corresponding representations of research activities, geographical contexts as well as research cooperation. It shows a great scientific interest, especially by North American and European scientists. The steady growth of research is explained by the high prevalence of arthrosis.

[Midwives and smoking--attitudes, smoking status and counselling competence in the course of training]. / Hebammen und Rauchen--Einstellungen, Rauchstatus und Beratungskompetenz im Ausbildungsverlauf.

Tobacco consumption is a major public health threat. Midwives can contribute to the reduction of tobacco use among pregnant women and young families. It can be assumed that personal smoking behaviour and knowledge of harmful effects influences counselling activities. The aim of this study was to assess smoking status, nicotine dependency and the will to change of midwifery students in german-speaking countries. Broad data on this population is not available so far. In 2010, a self-administered questionnaire survey was conducted among Austrian, German and Swiss midwifery schools. Sociodemographic characteristics, smoking habits, personal attitudes towards smoking, knowledge of cessation strategies, perceived self-efficacy and competence to counsel pregnant women regarding their smoking habits of midwifery trainees were examined. 1 126 students and 38 teaching midwives answered this questionnaire (RR=61.8%). 22.7% are daily or occasional smokers. 6.8% have to be considered as medium and heavy smokers. 98.1% consider cessation counselling for pregnant and breast-feeding women as a midwife's task, while 76.5% feel competent enough to do so. 75.5% rate cessation counselling through midwives as effective stop-smoking procedures compared to blurry knowledge on related health risks and effective stop-smoking strategies. The self-reported smoking prevalence is considerably lower than in previous studies and other populations. Knowledge of harmful effects and of effective treatment options needs improvement. Counselling competence needs to be included in a broader way in midwifery curricula.

[Health promotion within health care - analysis of employees' smoking habits, consequences for patient care and resources for future smoking cessation initiatives]. / Gesundheitsförderung im Gesundheitswesen - Analyse der Rauchgewohnheiten der Mitarbeiter, Konsequenzen für die Patientenbehandlung und Ressourcen für zukünftige Tabakentwöhnungsinitiativen.

Smoking is still one of the most dangerous and avoidable health risks. This study "Healthy air at work" analysed smoking habits, state of change, the influence of the diagnosis F.17.0 in patient treatment and estimation of subjective workloads and personal resources in health-care workers. Almost 2 000 questionnaires were analysed. 19.9% of this study population were smokers, while 26.4% were considered to be heavy or very heavy smokers. Half of the current smokers were willing to change, while the majority had already tried to quit multiple times. The most important motive to stop smoking was fear of consequences (44.4%), followed by other reasons (42.3%) (e. g., pregnancy) and expenses (33.9%). Protection against second-hand smoke was estimated mostly as very relevant, especially for patients. Being a role model in terms of tobacco consumption seems to be important for health-care workers. 61.3% of all health-care workers stated that patients' nicotine dependency had been diagnosed and out of these 46.5% say it is a relevant factor in therapy. 60% of all interviewed employees evaluated themselves as working quantitatively under heavy and very heavy workloads, while 20% had to deal with high qualitative challenges. In terms of future work ability and personal resources 75% were considerably optimistic. We did not find any relation in terms of workloads and smoking habits. Rather few health-care workers used nicotine replacement therapy during former cessation trials. Health-care workers could play an important role in the treatment and prevention of smoking dependency. This potential is not used to its full extent up to now.

[Exposure to smoke and its effects on pulmonary diseases]. / Effekte von Rauchexposition auf Lungenerkrankungen.

For many diseases, tobacco smoke is the most important risk factor. To understand the different risks concerning both quality and severity of the possible diseases, the differentiation between mainstream smoke, sidestream smoke and environmental tobacco smoke (ETS) is indispensable, since the different types of smoke are associated with different diseases. Before anything else, tobacco smoke is the main risk factor for the development of lung cancer and with restrictions for laryngeal and pharyngeal carcinomas as well. Moreover, the inhalation of tobacco smoke is of great importance in the genesis of chronic obstructive lung diseases (COPD). During recent years it has generally been acknowledged that ETS, besides a general activity in cancerogenesis also, seems to induce other morbidities. Nevertheless, when looking at the risks of smoking it has to be mentioned that the difficulty of gaining reliable information concerning quality and quantity of the smoking and the exposure to ETS is significant. That is why in many cases the relation between the dose of tobacco smoke and its effect is hard to make out. Not to be denied is the fact that both active and passive smoking has a great impact on the respiratory tract, which should be considered carefully when it comes to children being exposed to ETS. The age of children when exposed to regular ETS for the first time plays a key role concerning their disposition to later developing a COPD or a bronchial asthma. This subject of ETS is especially of great interest in the work of company doctors because there are many people exposed to ETS for many hours every day in their work environment. This problem is most obvious in the gastronomic work sector.

[Gene doping--current possibilities, risks and means of prevention]. / Gendoping--aktuelle Möglichkeiten, Risiken und Präventionskonzepte.

With the advances in gene therapy fears of an abuse in sports arise. The WADA's definition of the term strictly differentiates between gene doping and gene therapy. There are in vivo and ex vivo practices to manipulate the different phases of gene expression in the organism, with viral vectors being looked upon as the most efficient ones. IGF-1, PPARδ, MSTN and EPO play the most important roles in today's scientific research. Their potential was proven in various animal studies, showing a significant improvement of performances. Potential risks for human users include severe immune reactions, mutagenesis, and raised risk for cancer. Big efforts are being put into the development of ways of detection, however until now there are neither practicable methods of control nor any reported cases of manipulated humans. Still, a usage of gene doping that has already taken place cannot be ruled out and is highly likely.

Pituitary adenylate cyclase-activating peptide receptor 1 mediates anti-inflammatory effects in allergic airway inflammation in mice.

BACKGROUND: Bronchial asthma is characterized by airway inflammation and reversible obstruction. Since the gold standard of therapy, a combination of anti-inflammatory corticosteroids and bronchodilatory ß(2) agonists, has recently been discussed to be related to an increased mortality, there is a need for novel therapeutic pathways. OBJECTIVE: A new experimental concept that encompasses the vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide (PACAP) family of receptors by demonstrating the anti-inflammatory effects of the PACAP receptor 1 (PAC1R) in a murine model of allergic asthma is described. METHODS: PAC1R expression was investigated in lung tissue and isolated dendritic cells (DCs) via real-time PCR. Ovalbumin (OVA)-induced asthma models were used in PAC1R-deficient mice and BALB/c mice treated with PAC1R agonist maxadilan (MAX). Bronchoalveolar lavages have been performed and investigated at the cellular and cytokine levels. Fluorescence staining of a frozen lung section has been performed to detect eosinophil granulocytes in lung tissue. Plasma IgE levels have been quantified via the ELISA technique. Lung function was determined using head-out body plethysmography or whole-body plethysmography. RESULTS: Increased PAC1R mRNA expression in lung tissue was present under inflammatory conditions. PAC1R expression was detected on DCs. In OVA-induced asthma models, which were applied to PAC1R-deficient mice (PAC1R(-/-)) and to BALB/c mice treated with the specific PAC1R agonist MAX, PAC1R deficiency resulted in inflammatory effects, while agonistic stimulation resulted in anti-inflammatory effects. No effects on lung function were detected both in the gene-depletion and in the pharmacologic studies. In summary, here, we demonstrate that anti-inflammatory effects can be achieved via PAC1R. CONCLUSION: PAC1R agonists may represent a promising target for an anti-inflammatory therapy in airway diseases such as bronchial asthma.

[Health effects of particulate matter exposure: current scientific knowledge]. / Gesundheitliche Effekte der Feinstaubbelastung - aktueller wissenschaftlicher Kenntnisstand.

INTRODUCTION: Air quality is not only important for respiratory health but it also influences the homeostasis of the whole human organism. In the past years numerous violations of European Union particulate matter thresholds have been recorded. METHODS: The present study is a selective literature analysis encompassing the epidemiology and pathophysiological effects of particulate matter. RESULTS: Epidemiological studies point to an association between chronic particulate matter exposure and mortality. The most prominent effects on the human body are present in subjects with cardiovascular or respiratory conditions. However, the effects of air pollutants need to be examined critically and the plausibility of thresholds should be evaluated in detail. DISCUSSION: The negative influences of chronic particulate matter exposure have been proven by a multitude of epidemiological and experimental studies. From the viewpoint of primary prevention, air quality plays a crucial role. This encompasses both the outdoor compartment with particulate matter and other pollutants and the indoor compartment with tobacco smoke.

[Erythropoietin - state of science]. / Erythropoietin - aktueller Stand der Wissenschaft.

After a century of research and medical use, erythropoietin (EPO) has more therapeutic approaches than ever in history. After cloning its gene in 1984, EPO obtained FDA license for clinical use in 1989. EPO and its analogues are mainly used for treatment of the anaemias of chronic renal failure and malignancies. Regarding research of the past 15 years, tremendous efforts were made for improvement of bioactivity, half-life and alternative application. Today, there are human cell-lined derived EPO, SEP, CEPO, CERA and drugs which are linked to different pathways of signaling. Due to the fact that these substances are not detectable with standardized methods of detection, it must be assumed that the abuse in sport is still possible. Moreover it was found out that the EPO receptor and EPO synthesis are also expressed by non-hematopoietic tissues, e. g. heart myocytes, ovarian and glial cells. On these tissues EPO is linked to promote cell proliferation and differentiation, angiogenesis or inhibition of apoptosis. This detection offered approaches in treatment for apoplexia and cardiac infarction and even in preventive treatment of cardiovascular diseases which led to an interest of manifold subject categories.

Neurokinin-1 receptor activation induces reactive oxygen species and epithelial damage in allergic airway inflammation.

BACKGROUND: An induction of reactive oxygen species (ROS) is characteristic for inflammation but the exact pathways have not been identified for allergic airway diseases so far. OBJECTIVE: The aim of this study was to characterize the role of the tachykinin NK-1 receptor on ROS production during allergen challenge and subsequent inflammation and remodelling. METHODS: Precision-cut lung slices of ovalbumin (OVA)-sensitized mice were cultivated and ROS-generation in response to OVA challenge (10 microg/mL) was examined by the 2',7'-dichloroflourescein-diacetate method. Long-term ROS effects on epithelial proliferation were investigated by 5-bromo-2'-deoxyuridine incorporation (72 h). In vivo, the results were validated in OVA-sensitized animals which were treated intra-nasally with either placebo, the tachykinin neurokinin 1 (NK-1) receptor antagonist SR 140333 or the anti-oxidant N-acetylcystein (NAC) before allergen challenge. Inflammatory infiltration and remodelling were assessed 48 h after allergen challenge. RESULTS: ROS generation was increased by 3.7-fold, which was inhibited by SR 140333. [Sar(9),Met(11)(O(2))]-Substance P (5 nM) caused a tachykinin NK-1 receptor-dependent fourfold increase in ROS generation. Epithelial proliferation was decreased by 68% by incubation with [Sar(9),Met(11)(O(2))]-SP over 72 h. In-vivo, treatment with SR 140333 and NAC reduced epithelial damage (91.4% and 76.8% vs. placebo, respectively, P<0.01) and goblet cell hyperplasia (67.4% and 50.1% vs. placebo, respectively, P<0.05), and decreased inflammatory cell influx (65.3% and 45.3% vs. placebo, respectively, P<0.01). CONCLUSION: Allergen challenge induces ROS in a tachykinin NK-1 receptor-dependent manner. Inhibition of the tachykinin NK-1 receptor reduces epithelial damage and subsequent remodelling in vivo. Therefore, patients may possibly benefit from treatment regime that includes radical scavengers or tachykinin NK-1 receptor antagonists.

[COPD--chronic obstructive pulmonary disease and its implications for the human organism]. / COPD--die chronisch obstruktive Lungenerkrankung und ihre Auswirkungen auf den Organismus.

Chronic obstructive pulmonary disease (COPD) belongs next to bronchial asthma to the most important diseases of the respiratory tract in terms of its socio-economic impact. Especially exacerbations of COPD and clinical end-stages exert extremely negative effects on the global burden of disease. This article analyses current aspects of COPD regarding epidemiology, pathogenesis, pathophysiology and diagnosis of the disease. Given the estimation that COPD will be the third most common cause of death in the year 2020, the high socio-economic costs and the primary cause tobacco smoke exposure, the disease can be regarded as extremely relevant for numerous aspects of insurance medicine.

Airway hyper-responsiveness in allergic asthma in guinea-pigs is mediated by nerve growth factor via the induction of substance P: a potential role for trkA.

BACKGROUND: The neurotrophin nerve growth factor (NGF) has been implicated as a mediator in allergic asthma. Direct evidence that inhibition of NGF-induced activation of neurotrophin receptors leads to improvement of airway symptoms is lacking. We therefore studied the effects of inhibitors of NGF signal transduction on the development of airway hyper-responsiveness (AHR) and pulmonary inflammation in a guinea-pig model for allergic asthma. METHODS: Airway responsiveness to the contractile agonist histamine was measured in vivo in guinea-pigs that were sensitized and challenged with ovalbumin (OVA). Inflammatory cell influx and NGF levels were determined in bronchoalveolar lavage fluid (BALF). Substance P, a key mediator of inflammation, was measured in lung tissue by radioimmunoassay, while substance P immunoreactive neurons in nodose ganglia were measured by immunohistochemistry. RESULTS: OVA challenge induced an AHR after 24 h in OVA-sensitized guinea-pigs. This coincided with an increase in the amount of NGF in BALF. Simultaneously, an increase in the percentage of substance P immunoreactive neurons in the nodose ganglia and an increase in the amount of substance P in lung tissue were found. We used tyrosine kinase inhibitors to block the signal transduction of the high-affinity NGF receptor, tyrosine kinase A (trkA). Treatment with the tyrosine kinase inhibitors (K252a or tyrphostin AG879) both inhibited the development of AHR, and prevented the increase in substance P in the nodose ganglia and lung tissue completely whereas both inhibitors had no effect on baseline airway resistance. Neither treatment with K252a or tyrphostin AG879 changed the influx of inflammatory cells in the BALF due to allergen challenge. CONCLUSIONS: We conclude that substance P plays a role in the induction of AHR in our model for allergic asthma which is most likely mediated by NGF. As both tyrosine kinase inhibitors AG879 and K252a show a similar inhibitory effect on airway function after allergen challenge, although both tyrosine kinase inhibitors exhibit different non-specific inhibitory effects on targets other than trkA tyrosine kinases, it is likely that the induction of substance P derived from sensory nerves is mediated by NGF via its high-affinity receptor trkA.

Amelioration of anemia after kidney transplantation in severe secondary oxalosis.

INTRODUCTION: In small bowel disease such as M. Crohn, the intestinal absorption of oxalate is increased. Severe calcium oxalate deposition in multiple organs as consequence of enteric hyperoxaluria may lead to severe organ dysfunction and chronic renal failure. The management of hemodialyzed patients with short bowel syndrome may be associated with vascular access problems and oxalate infiltration of the bone marrow leading to pancytopenia. Although the risk of recurrence of the disease is very high after renal transplantation, it may be the ultimate therapeutic alternative in secondary hyperoxaluria. CASE: Here, we report a patient with enteric oxalosis due to Crohn's disease. He developed end-stage renal disease, erythropoietin-resistant anemia, oxalate infiltration of the bone marrow and severe vascular access problems. Following high-urgency kidney transplantation, daily hemodiafiltration of 3 hours was performed for 2 weeks to increase oxalate clearance. Despite tubular and interstitial deposition of oxalate in the renal transplant, the patient did not require further hemodialysis and the hematocrit levels normalized. DISCUSSION: Early treatment of hyperoxaluria due to short bowel syndrome is essential to prevent renal impairment. Declining renal function leads to a further increase in oxalate accumulation and consecutive oxalate deposition in the bone marrow or in the vascular wall. If alternative treatments such as special diet or daily hemodialysis are insufficient, kidney transplantation may be a therapeutic alternative in severe cases of enteric oxalosis despite a possible recurrence of the disease.

[Air quality and particulate matter]. / Luftqualität und Feinstaubbelastung.

Clean air is considered to be a key factor influencing human health. It is not only important for respiratory health but influences the homeostasis of the whole human organism. In this respect, all major national and international respiratory societies point to the extremely important role of national and international clean air acts that address both inner (i. e. tobacco smoke) and outer (i. e. environmental pollutants) air pollution. Due to research at the levels of pulmonary medicine and environmental medicine, the European Union has implemented new limit values. Clinical and experimental evidence points out that it is crucial to comply with these regulations since recent studies have shown that not only patients with lung diseases but also children and their lung development are endangered by high concentrations of air pollutants. With regard to the complexity of detrimental effects new national and international research programs should be established for the assessment of health effects of air pollutants.

[Drug transport in the respiratory epithelium]. / Pharmakatransport im Atemwegsepithel.

The aerosolic administration of peptidomimetic drugs with a peptide backbone may play a crucial role in the future treatment of diseases. Especially rational drug design offers an option to synthesize new drugs that are carried by specific drug transporters. Out of the presently identified transporter proteins PEPT1 and PEPT2, the high-affinity transporter PEPT2 is found in the respiratory tract. The transporter possess 12 membrane spanning domains and catalyses an electrogenic uphill drug transport using a transmembrane electrochemical proton gradient. PEPT2 is expressed in the bronchial epithelium and in alveolar type II pneumocytes in human airways. Kinetic studies demonstrated that peptidomimetic compounds including antibiotic, antiviral and antineoplastic drugs are carried by PEPT2. The transporter also carries delta-aminolevulinic acid into the airways. This molecule can be used for the diagnostics of pulmonary neoplasms and for photodynamic therapy. Using the recently published data on minimal structural requirements for PEPT2-substrates, rational drug design may lead to a new generation of respiratory drugs and prodrugs, which are delivered to the airways via the molecular mechanisms of the PEPT2 transport system.

Gene expression and regulation of transcription factor activator protein-2 alpha in human mast cells.

BACKGROUND: The transcription factor activator protein (AP)-2 regulates cell-type specific gene expression during development and differentiation, but its role in mast cell development has so far not been explored. METHODS: Gene expression and regulation of AP2 was assessed in normal skin, diseases with increased mast cell numbers, and in vitro models of mast cell differentiation. RESULTS: AP-2alpha-protein was not detectable in normal skin but in mastocytoma lesional mast cells. AP-2alpha-mRNA and -protein were also detected in leukemic mast cells (HMC-1), in the adherent fraction of peripheral blood (PBMC) and umbilical cord blood mononuclear cells (CBMC), and AP-2alpha-mRNA at low levels in isolated-purified mast cells. During culture with fibroblast supernatants or SCF, AP-2alpha-mRNA was de novo expressed in KU812-cells, maintained at about the same level in PBMC and CBMC, and upregulated in HMC-1-cells. On extended culture, a down-regulation was noted at mRNA and/or protein levels. In contrast, tryptase expression increased in all cells throughout culture, as did c-Kit in normal cells, whereas in both leukemic cell lines, c-Kit was maintained unchanged at about the same level. CONCLUSIONS: These findings suggest a continuous activation of AP-2alpha in mastocytomas and mast cell leukemia and its transient upregulation during c-Kit dependent early steps of normal mast cell differentiation.

Neurogenic mechanisms in bronchial inflammatory diseases.

Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD.