Premature departure from nursing in Germany as a growing problem for the health care system -- a review

There is a shortage of nursing staff in almost all of the countries in the European Union. This problem is expected to increase within the next decades as a result of demographic changes. Efforts to improve training or recruiting nurses from other countries such as future EU member states are unlikely to solve the problem. Premature departure from the nursing profession occurs more frequently than in other professional fields in Germany. There is little known about the underlying reasons of this. The authors present data regarding the early departure of nursing staff from the profession. They propose that a lengthened stay in nursing could help solve the above problem. In order for specific measures to take place (to solve this), more knowledge is needed regarding the causes and circumstances surrounding the early departure of nursing staff. This is the object of the European NEXT-Study ( http://www.next-study.net ), in which research groups from 10 European countries are taking part. Starting in Autumn 2002, between 5000 and 8000 nurses will be questioned in each of the 9 countries, in this longitudinal study. The first findings will be submitted in Summer 2003.     

Alteration of pulmonary cytochrome p-450 system: effects of asphalt fume condensate exposure

Exposure to asphalt fumes is a health concern due to the presence of polycyclic aromatic compounds (PACs) in asphalt. Bioactivation of many PACs requires metabolism by the cytochrome P-450 (P-450) system. The objective of this study was to evaluate the effects of exposure of rats to asphalt fume condensate (AFC), collected at the top of a paving asphalt storage tank, on the pulmonary microsomal P-450 system and to determine the genotoxic effects of such exposure. Male Sprague-Dawley rats were intratracheally instilled with saline or with 0.45, 2.22, or 8.88 mg/kg AFC for 3 consecutive days and sacrificed the following day. Lung microsomes were isolated by differential centrifugation of lung homogenates. Microsomal protein level, NADPH cytochrome c reductase activity, and the activities and protein levels of cytochrome P-450 isozymes CYP1A1 and CYP2B1 were monitored to assess the effects of AFC exposure on pulmonary P-450. The activities of CYP2B1 and CYP1A1 were determined by monitoring xenobiotic metabolism of 7-pentoxyresorufin and 7-ethoxyresorufin, respectively. CYP2B1 and CYP1A1 levels were determined by immunochemical analysis. Micronucleus (MN) formation in bone-marrow polychromatic erythrocytes (PCEs) was determined to assess the genotoxic effects of AFC exposure. The results showed that exposure of rats to AFC did not significantly affect total cytochrome P-450 content or cytochrome c reductase activity in the lung. CYP2B1 levels and enzyme activity were not significantly affected by AFC exposure. In contrast, CYP1A1 levels and activity were significantly increased in microsomes isolated from AFC-exposed lungs. Increased MN formation was observed only in high-dose AFC-exposed bone marrow PCEs. These results demonstrate that AFC exposure induced CYP1A1 activity and increased the enzyme levels of CYP1A1 in lung microsomes, suggesting that AFC exposure may alter metabolism of PACs by the cytochrome P-450 system in the lung. Alteration of cytochrome P-450 metabolism of PACs may contribute to the AFC-induced genotoxic effects demonstrated as MN formation.     

Leisure time physical activity is associated with poor glycemic control in type 1 diabetic women: the FinnDiane study

OBJECTIVE: We studied the association between leisure time physical activity (LTPA) and glycemic control, insulin dose, and estimated glucose disposal rate (eGDR) in type 1 diabetes. RESEARCH DESIGN AND METHODS: This is a cross-sectional study of 1,030 type 1 diabetic patients participating in the Finnish Diabetic Nephropathy Study, a nationwide multicenter study. LTPA was assessed by a validated 12-month questionnaire and expressed in metabolic equivalent (MET) units. Patients were grouped as sedentary (LTPA <10 MET h/week, n = 247), moderately active (LTPA 10-40 MET h/week, n = 568), and active (LTPA >40 MET h/week, n = 215). Outcome measures were HbA(1c), insulin dose, and eGDR (estimate of insulin sensitivity based on waist-to-hip ratio, hypertension, and HbA(1c)). RESULTS: LTPA correlated with HbA(1c) in women (r = -0.12, P = 0.007) but not in men (r = -0.03, P = 0.592). Sedentary women had higher HbA(1c) than moderately active and active women: 8.8 +/- 1.4% vs. 8.3 +/- 1.4% vs. 8.3 +/- 1.4% (P = 0.004), whereas HbA(1c) in men was 8.4 +/- 1.3% vs. 8.2 +/- 1.4% vs. 8.2 +/- 1.3% (P = 0.774), respectively. In men, insulin doses were 0.74 +/- 0.21 vs. 0.71 +/- 0.20 vs. 0.68 +/- 0.23 IU . kg(-1) . 24 h(-1) (P = 0.003). In both sexes, sedentary patients had lower eGDRs than active patients [median (interquartile range) 5.5 (4.0-8.2) vs. 6.8 (4.7-8.8) vs. 6.7 (4.6-8.6) mg . kg(-1) . min(-1); P < 0.01 for sedentary vs. others]. Age, obesity, smoking, insulin dose, social class, diabetic nephropathy, or cardiovascular disease did not explain the results. CONCLUSIONS: Low levels of LTPA were associated with poor glycemic control in type 1 diabetic women. Men seem to use less insulin when physically active. Increased LTPA levels were associated with increased estimated insulin sensitivity. Longitudinal studies are needed to further clarify the effects of LTPA on type 1 diabetes.     

A simple model for variant congenital cardiac anomalies

BACKGROUND: Traditionally, echocardiography, computed tomography and angiocardiography are used to detect the anatomy of congenital cardiac defects. Either pediatric cardiologists or cardiac surgeons mentally reconstruct these images into a vague imaginary three-dimensional heart, but such an image usually includes unnecessary surrounding structures which may mask the defects to be detected. METHOD: We use a perspective view model to draw a more stereoscopic picture of complex hearts instead of the simple two-dimensional sketch. With this model we have the ability to display cardiovascular anatomy in a three-dimensional structure to increase the understanding and appreciation of the complex spatial relationships in the majority of congenital hearts. RESULTS: Through these drawn images the physiology and structural defects of hearts may be understood more easily and explained more clearly in comparison to two-dimensional representations. CONCLUSION: The simple perspective drawing is not used to replace the three-dimensional examinations, but it is helpful in reconstructing a model of the heart based on the information we obtain through serial examinations, and such a model may be used to teach medical students, as well as to explain defects to patients' families.     

Antiangiogenic therapy in brain tumors

Angiogenesis, the recruitment of new blood vessels, is an essential component of tumor progression. Malignant brain tumors are highly vascularized and their growth is angiogenesis-dependent. As such, inhibition of the sprouting of new capillaries from pre-existing blood vessels is one of the most promising antiglioma therapeutic approaches. Numerous classes of molecules have been implicated in regulating angiogenesis and, thus, novel agents that target and counteract angiogenesis are now being developed. The therapeutic trials of a number of angiogenesis inhibitors as antiglioma drugs are currently under intense investigation. Preliminary studies of angiogenic blockade in glioblastoma have been promising and several clinical trials are now underway to develop optimum treatment strategies for antiangiogenic agents. This review will cover state-of-the-art antiangiogenic targets for brain tumor treatment and discuss future challenges. An increased understanding of the angiogenic process, the diversity of its inducers and mediators, appropriate drug schedules and the use of these agents with other modalities may lead to radically new treatment regimens to achieve maximal efficacy.     

Differential oncogenic potential of activated RAS isoforms in melanocytes

RAS genes are mutated in approximately 30% of all human cancers. Interestingly, there exists a strong bias in favor of mutation of only one of the three major RAS genes in tumors of different cellular origins. NRAS mutations occur in approximately 20% of human melanomas, whereas HRAS and KRAS mutations are rare in this disease. To define the mechanism(s) responsible for this preference in melanocytes, we compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. Although both NRAS and KRAS activate mitogen-activated protein kinase signaling, only NRAS enhances MYC activity in these cells. Our data suggest that the activity of specific RAS isoforms is context-dependent and provide a possible explanation for the prevalence of NRAS mutations in melanoma. In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways.     

MMP-2 siRNA induced Fas/CD95-mediated extrinsic II apoptotic pathway in the A549 lung adenocarcinoma cell line

We have previously reported that the downregulation of MMP-2 by adenovirus-mediated delivery of MMP-2 siRNA (Ad-MMP-2) reduced spheroid invasion and angiogenesis in vitro, and, metastasis and tumor growth in vivo. In this study, we investigated the mechanism of Ad-MMP-2-mediated growth inhibition in vitro and in vivo. Ad-MMP-2 infection led to the induction of apoptosis as determined by TUNEL assay, Annexin-V staining and PARP-1 cleavage in a dose-dependent manner in A549 cells. Ad-MMP-2 decreased the content of the antiapoptotic members of the Bcl-2 family proteins (Bcl-2 and Bcl-xL) and increased the content of the pro-apoptotic members of the Bcl-2 family (Bax and Bcl-xS) as determined by immunoblotting analysis. Furthermore, Ad-MMP-2-mediated apoptosis was accompanied by increase in truncated Bid, release of cytochrome c and the activation of caspase-8, -9 and -3. Immunoblot analysis showed that Ad-MMP-2 infection caused upregulation of Fas/Fas-L and FADD, and Anti-Fas-L antibody reversed Ad-MMP-2-induced apoptosis. Tissue inhibitor of metalloproteinases (TIMP)-3, an endogenous inhibitor of MMP-2, which cleaves Fas-L and activates the Fas/Fas-L inducing apoptotic pathway, was increased in Ad-MMP-2-treated cells. Adenovirus-mediated expression of MMP-2 siRNA in human lung xenografts in vivo resulted in increased immunostaining of Fas, Fas-L, cleaved Bid and TIMP-3. This is the first report, to our knowledge, showing that MMP-2 inhibition upregulates TIMP-3 levels, which in turn, promotes apoptosis in lung cancer.