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Tumor progression and pregnancy share many common features, such as immune tolerance and invasion. The invasion of trophoblasts in the placenta into the uterine wall is essential for fetal development, and is thus precisely regulated. Its deregulation has been implicated in preeclampsia, a leading cause for maternal and perinatal mortality and morbidity. Pathogenesis of preeclampsia remains to be defined. Microarray-based gene profiling has been widely used for identifying genes responsible for preeclampsia. In this review, we have summarized the recent data from the microarray studies with preeclamptic placentas. Despite the complex of gene signatures, suggestive of the heterogeneity of preeclampsia, these studies identified a number of differentially expressed genes associated with preeclampsia. Interestingly, most of them have been reported to be tightly involved in tumor progression. We have discussed these interesting genes and analyzed their potential molecular functions in preeclampsia, compared with their roles in malignancy development. Further investigations are warranted to explore the involvement in molecular network of each identified gene, which may provide not only novel strategies for prevention and therapy for preeclampsia but also a better understanding of cancer cells. The trophoblastic cells, with their capacity for proliferation and differentiation, apoptosis and survival, migration, angiogenesis and immune modulation by exploiting similar molecular pathways, make them a compelling model for cancer research.
The impact of shift work induced chronic circadian disruption on IL-6 and TNF-α immune responses
(2010)
Mark, Anke van ; Weiler, Stephan W. ; Schröder, Marcel ; Otto, Andreas ; Jauch-Chara, Kamila ; Groneberg, Jan David Alexander ; Spallek, Michael ; Kessel, Richard ; Kalsdorf, Barbara
Aim: Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far.
Methods: Pittsburgh-Sleep-Quality-Index (PSQI) questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-alpha and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview.
Results: Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p < 0.001). Day workers and shift workers had similar serum levels of IL-6 (2.30 vs. 2.67 resp.; p = 0.276), TNF-alpha (5.58 vs. 5.68, resp.; p = 0.841) or lymphocytes count (33.68 vs. 32.99, resp.; p = 0.404). Furthermore there were no differences in cytokine levels (IL-6 p = 0.761; TNF-alpha p = 0.759) or lymphocyte count (p = 0.593) comparing the sleep quality within the cohorts. When this calculation of sleep quality was stratified by shift and day workers irrespective of their sleep quality day workers and shift workers had similar serum levels of IL-6, TNF-alpha or lymphocytes count. Multiple linear regression analysis showed a significant correlation of lymphocytes count and smoking habits.
Conclusion: Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-alpha serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy) protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.
Mache, Stefanie ; Scutaru, Cristian ; Vitzthum, Karin ; Quarcoo, David ; Schöffel, Norman ; Welte, Tobias ; Klapp, Burghard F. ; Groneberg, Jan David Alexander
Background: During the last two decades the German hospital sector has been engaged in a constant process of transformation. One obvious sign of this is the growing amount of hospital privatization. To date, most research studies have focused on the effects of privatization regarding financial outcomes and quality of care, leaving important organizational issues unexplored. Yet little attention has been devoted to the effects of privatization on physicians' working routines. The aim of this observational real-time study is to deliver exact data about physicians' work at hospitals of different ownership. By analysing working hours, further impacts of hospital privatization can be assessed and areas of improvement identified.
Methods: Observations were made by shadowing 100 physicians working in private, for-profit or non-profit as well as public hospital departments individually during whole weekday shifts in urban German settings. A total of 300 days of observations were conducted. All working activities were recorded, accurate to the second, by using a mobile personal computer.
Results: Results have shown significant differences in physicians' working activities, depending on hospital ownership, concerning working hours and time spent on direct and indirect patient care.
Conclusion: This is the first real-time analysis on differences in work activities depending on hospital ownership. The study provides an objective insight into physicians' daily work routines at hospitals of different ownership, with additional information on effects of hospital privatization.
Vitzthum, Karin ; Mache, Stefanie ; Quarcoo, David ; Scutaru, Cristian ; Groneberg, Jan David Alexander ; Schöffel, Norman
Background: Publications related to scoliosis have increased enormously. A differentiation between publications of major and minor importance has become difficult even for experts. Scientometric data on developments and tendencies in scoliosis research has not been available to date. The aim of the current study was to evaluate the scientific efforts of scoliosis research both quantitatively and qualitatively.
Methods: Large-scale data analysis, density-equalizing algorithms and scientometric methods were used to evaluate both the quantity and quality of research achievements of scientists studying scoliosis. Density-equalizing algorithms were applied to data retrieved from ISI-Web.
Results: From 1904 to 2007, 8,186 items pertaining to scoliosis were published and included in the database. The studies were published in 76 countries: the USA, the U.K. and Canada being the most productive centers. The Washington University (St. Louis, Missouri) was identified as the most prolific institution during that period, and orthopedics represented by far the most productive medical discipline. "BRADFORD, DS" is the most productive author (146 items), and "DANSEREAU, J" is the author with the highest scientific impact (h-index of 27).
Conclusion: Our results suggest that currently established measures of research output (i.e. impact factor, h-index) should be evaluated critically because phenomena, such as self-citation and co-authorship, distort the results and limit the value of the conclusions that may be drawn from these measures. Qualitative statements are just tractable by the comparison of the parameters with respect to multiple linkages. In order to obtain more objective evaluation tools, new measurements need to be developed.
Mingomataj, Ervin ; Priftanji, Alfred ; Qirko, Etleva ; Dinh, Q. Thai ; Fischer, Axel ; Peiser, Christian ; Groneberg, Jan David Alexander
Background: Severe allergic reactions during rush-specific immunotherapy (Rush-SIT) may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during Rush-SIT in a cohort of patients with allergy towards hymenoptera venom in the mediterranean population of Albania.
Methods: A retrospective study was performed using the clinical reports of 37 patients with venom of bee (apinae), wasp (vespidae, subfamily vespinae) or paperwasp (vespidae, subfamily polistinae) allergy treated with Rush-SIT between 1987 and 1996. After hymenoptera sting allergy diagnosis according to anamnesis and intracutaneous tests the patient were treated with Rush-SIT. The protocol lasted 3 - 4 d with an increase in the concentration from 0.01 microg/ml to 100 microg/ml. Anaphylactic reactions were classified according to the Mueller-classification.
Results: The frequency of reactions during Rush-SIT for bee-venom was 4.7% and for wasp-venom was 1.5% (p < 0.01). The mean frequency of reactions of Mueller grade II for the bee-venom Rush-SIT patients during the first 4 d (= 26 injections) was 0.73 and for the wasp-venom Rush-SIT patients 0.15. No patient experienced a third-degree reaction. 94.6% of the patient supported an end dose of 100 microg.
Conclusions: Rush-SIT is a reliable method for the treatment of anaphylactic reactions to hymenoptera venom even in less developed countries. Bee-venom Rush-SIT was found to cause higher numbers allergic reactions than wasp or paperwasp Rush-SIT.
Background: The increasing economic pressure characterizes the current situation in health care and the need to justify medical decisions and organizational processes due to limited financial resources is omnipresent. Physicians tend to interpret this development as a decimation of their own medical influence. This becomes even more obvious after a change in hospital ownership i.e. from a public to a private profit oriented organization. In this case each work procedure is revised.
To date, most research studies have focused mainly on differences between hospitals of different ownership regarding financial outcomes and quality of care, leaving important organizational issues unexplored. Little attention has been devoted to the effects of hospital ownership on physicians' working routines.
The aim of this observational real time study is to deliver exact data about physicians' work at hospitals of different ownership.
Methods: The consequences of different management types on the organizational structures of the physicians' work situation and on job satisfaction in the ward situation are monitored by objective real time studies and multi-level psycho diagnostic measurements.
Discussion: This study is unique in its focus. To date no results have been found for computer-based real time studies on work activity in the clinical field in order to objectively evaluate a physician's work-related stress. After a complete documentation of the physicians' work processes the daily work flow can be estimated and systematically optimized. This can stimulate an overall improvement of health care services in Germany.
Mache, Stefanie ; Scutaru, Cristian ; Vitzthum, Karin ; Gerber, Alexander ; Quarcoo, David ; Welte, Tobias ; Bauer, Torsten Thomas ; Spallek, Michael ; Seidler, Andreas ; Nienhaus, Albert ; Klapp, Burghard F. ; Groneberg, Jan David Alexander
Background: There are several ways to conduct a job task analysis in medical work environments including pencil-paper observations, interviews and questionnaires. However these methods implicate bias problems such as high inter-individual deviations and risks of misjudgement. Computer-based observation helps to reduce these problems. The aim of this paper is to give an overview of the development process of a computer-based job task analysis instrument for real-time observations to quantify the job tasks performed by physicians working in different medical settings. In addition reliability and validity data of this instrument will be demonstrated.
Methods: This instrument was developed in consequential steps. First, lists comprising tasks performed by physicians in different care settings were classified. Afterwards content validity of task lists was proved. After establishing the final task categories, computer software was programmed and implemented in a mobile personal computer. At least inter-observer reliability was evaluated. Two trained observers recorded simultaneously tasks of the same physician.
Results: Content validity of the task lists was confirmed by observations and experienced specialists of each medical area. Development process of the job task analysis instrument was completed successfully. Simultaneous records showed adequate interrater reliability.
Conclusion: Initial results of this analysis supported the validity and reliability of this developed method for assessing physicians' working routines as well as organizational context factors. Based on results using this method, possible improvements for health professionals' work organisation can be identified.
Since 2002, a workshop entitled “Asthma in animal models” has been held once a year in Hannover, Germany. It is organized by the Fraunhofer Institute of Toxicology and Experimental Medicine in collaboration with the collaborative research centre “Sonderforschungsbereich” 587, “Immune reactions of the lung in infection and allergy” (Hannover Medical School). The aim of these meetings is an intense scientific exchange between researchers and clinicians coming from academic or industrial background. Over the years the topics within the extensive field of asthma and COPD have ranged from methodological aspects to the influence of infections and environmental factors up to perspectives in the development of new therapeutic strategies.
Within the large variety of subtypes of chronic cough, either defined by their clinical or pathogenetic causes, occupational chronic cough may be regarded as one of the most preventable forms of the disease. Next to obstructive airway diseases such as asthma or chronic obstructive pulmonary disease, which are sometimes concomitant with chronic cough, this chronic airway disease gains importance in the field of occupational medicine since classic fiber-related occupational airway diseases will decrease in the future.
Apart from acute accidents and incidental exposures which may lead to an acute form of cough, there are numerous sources for the development of chronic cough within the workplace. Over the last years, a large number of studies has focused on occupational causes of respiratory diseases and it has emerged that chronic cough is one of the most prevalent work-related airway diseases. Best-known examples of occupations related to the development of cough are coal miners, hard-rock miners, tunnel workers, or concrete manufacturing workers.
As chronic cough is often based on a variety of non-occupational factors such as tobacco smoke, a distinct separation into either occupational or personally -evoked can be difficult. However, revealing the occupational contribution to chronic cough and to the symptom cough in general, which is the commonest cause for the consultation of a physician, can significantly lead to a reduction of the socioeconomic burden of the disease.
Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
(2012)
Weißmann, Norbert ; Sydykov, Akylbek ; Kalwa, Hermann ; Storch, Ursula ; Fuchs, Beate ; Mederos y Schnitzler, Michael ; Brandes, Ralf ; Grimminger, Friedrich ; Meissner, Marcel ; Freichel, Marc ; Offermanns, Stefan ; Veit, Florian ; Pak, Oleg ; Krause, Karl-Heinz ; Schermuly, Ralph T. ; Brewer, Alison C. ; Schmidt, Harald H. H. W. ; Seeger, Werner ; Shah, Ajay M. ; Gudermann, Thomas ; Ghofrani, Hossein A. ; Dietrich, Alexander
Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE.