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This paper summarises the view of the German Commission on Radiological Protection ("Strahlenschutzkommission", SSK) on the rationale behind the currently valid dose limits and dose constraints for workers recommended by the International Commission on Radiological Protection (ICRP). The paper includes a discussion of the reasoning behind current dose limits followed by a discussion of the detriment used by ICRP as a measure for stochastic health effects. Studies on radiation-induced cancer are reviewed because this endpoint represents the most important contribution to detriment. Recent findings on radiation-induced circulatory disease that are currently not included in detriment calculation are also reviewed. It appeared that for detriment calculations the contribution of circulatory diseases plays only a secondary role, although the uncertainties involved in their risk estimates are considerable. These discussions are complemented by a review of the procedures currently in use in Germany, or in discussion elsewhere, to define limits for genotoxic carcinogens. To put these concepts in perspective, actual occupational radiation exposures are exemplified with data from Germany, for the year 2012, and regulations in Germany are compared to the recommendations issued by ICRP. Conclusions include, among others, considerations on radiation protection concepts currently in use and recommendations of the SSK on the limitation of annual effective dose and effective dose cumulated over a whole working life.

This special issue of JRP includes a selection of research papers and review articles presented at the 15th Congress of the International Radiation Protection Association (IRPA15) as chosen by the scientific committee. All invited journal contributions are suitably expanded beyond the initial conference presentations to meet the criteria for a full journal article and include (a) presentation within a comprehensive radiological protection context and (b) additional data/interpretation. Published contributions address a wide spectrum of scientific topics and concepts to further develop the radiation protection (RP) system. They are based on scientific evidence and available experience in a wide spectrum of applications of the protection system. The IRPA is the international voice of the RP profession. It promotes excellence in RP by providing benchmarks of good practice, enhancing professional competence, and encourages the application of the highest standards of professional conduct, skills and knowledge for the benefit of individuals and society. Within the overarching theme of the conference ‘Bridging RP Culture and Science—Widening Public Empathy’ IRPA15 provided an invaluable opportunity to discuss and strengthen the relations between RP culture and science, and share developing scientific knowledge and related experience in RP among members of the scientific community, between representatives of key international organizations, including ICRP, IAEA, WHO, and NEA but also with the public. Some discussions focused on the rationale of available RP programmes and priorities, with an opportunity to identify and further develop key scientific issues of the current RP system as well as key processes for the interaction between members of the scientific community and society. The scientific programme of IRPA15 included eight topics and four thematic areas. The topical areas were: Underpinning Science; Dosimetry and Measurement; the System of Protection; Standards and Regulation; Practical Implementation—Medical Sector, as well as Industry and Research; Emergency Preparedness and Response; Existing Exposures and Non-ionizing Radiation. The thematic areas addressed were: Ethics; Communication and Public Understanding; RP Culture; Human Capital and Competency.

Diagnostic medical exposures are intentional and they are applied to result in a direct benefit of the patient. In radiation therapy, the biological effects of high-dose radiation are used for the ...

Observations and lessons identified after the Fukushima accident have been collected and assessed by ICRP Task Group 84. Together with the observations of other expert organizations, they are being used to further develop the current system of protection. While many of the established protection criteria remain valid, improvements are needed in three areas. Key issues related to the need of planning for long-term protective actions (criteria for returning home, dealing with waste) have to be implemented as important elements of the national protection strategies during the preparedness stage. The justification of disruptive protective actions and the protection of vulnerably groups of the population need to be reconsidered to avoid unpleasant imbalances and outcomes. The coexistence of radiation-induced health effects and health effects with social determinants requires consideration of both aspects in decision-making and response.

At its 58th session in May 2011, the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR) decided to carry out, once sufficient information was available, a full assessment of the levels of exposure and radiation risks attributable to the Fukushima accident. It envisages a preliminary document for consideration at its 59th session in May of 2012 and a more complete report for the 60th session of the Committee in 2013. This paper summarises the aims and objectives of the project, the scope, the working arrangements as well as the relation of the work to other activities.

The purpose of the present study was to assess the course of adhesion molecules (intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), e-selectin, p-selectin and monocyte chemoatlractant protein 1 (MCP-1)), growth factors (transforming growth factor beta (TGFbeta) and basic fibroblast growth factor (bFGF)) and the cytokine tumour necrosis factor alpha (TNFalpha) after both angioplasty and cryoplasty. Recently cryoplasty has been suggested as a new method to oppose neointimal hyperplasia resulting in restenosis formation. While in vitro models have shown that the application of cryothermal energy to the endothelium during angioplasty leads to apoptosis induction and reduced proliferation rates, no human in vivo proof for an inhibition of neointimal hyperplasia exists. For restenosis initiation adhesion molecules, growth factors and cytokines play an important role. One possibility to investigate the endothelial response to angioplasty is the measurement of the soluble forms of adhesion molecules, growth factors and cytokines that are released into the circulation after denuding the vessel wall. In the present study we assessed the distribution pattern of the soluble forms of e-selectin, p-selectin, ICAM, VCAM, MCP-1, TGFbeta, bFGF and TNFalpha after angiography, angioplasty and cryoplasty of the femoropopliteal artery in the early course of 4 weeks in 29 patients with peripheral arterial occlusive disease. During the 4 weeks after intervention levels of e-selectin, ICAM, VCAM and MCP-1 increased after both angioplasty and cryoplasty. The course of the screened biomarkers was similar between angioplasty and cryoplasty. P-selectin and TGFbeta both decreased after cryoplasty, but not significantly. The present results show that the release of adhesion molecules, growth factors and cytokines is similar between balloon angioplasty and cryoplasty.

To evaluate survival and toxicity rates after primary external-beam radiation for the treatment of prostate cancer. Data of 306 patients treated with conformal external beam radiation between 1996 and 2001 were collected. These were evaluated in terms of overall, cause-specific and disease-free survival as well as toxicity. Furthermore, an investigation of possible risk factors was performed. Toxicity rates compared favorably with other series with 5.2% RTOG 1–2 and no RTOG > 2 long-term side effects. Actuarial 5-year overall survival rates with and without biochemical failure were 77% versus 78%, cancer-specific survival was 85.41% versus 100%, and disease-free survival was 71.54%, respectively. Potential risk factors for cancer-related death were biochemical failure, initial serum prostate-specific antigen (PSA) and Gleason score. Toxicity rates were found to be surprisingly low compared to other series, which is likely due to low daily dose and consistent MR-based treatment planning. In terms of survival, no significant differences to other trials could be observed. Initial PSA and Gleason score were significant predictors for treatment outcome in terms of survival.

In clinical development stages, an a priori assessment of the sensitivity of the pharmacokinetic behavior with respect to physiological and anthropometric properties of human (sub-) populations is desirable. A physiology-based pharmacokinetic (PBPK) population model was developed that makes use of known distributions of physiological and anthropometric properties obtained from the literature for realistic populations. As input parameters, the simulation model requires race, gender, age, and two parameters out of body weight, height and body mass index. From this data, the parameters relevant for PBPK modeling such as organ volumes and blood flows are determined for each virtual individual. The resulting parameters were compared to those derived using a previously published model (P(3)M). Mean organ weights and blood flows were highly correlated between the two models, despite the different methods used to generate these parameters. The inter-individual variability differed greatly especially for organs with a log-normal weight distribution (such as fat and spleen). Two exemplary population pharmacokinetic simulations using ciprofloxacin and paclitaxel as model drugs showed good correlation to observed variability. A sensitivity analysis demonstrated that the physiological differences in the virtual individuals and intrinsic clearance variability were equally influential to the pharmacokinetic variability but were not additive. In conclusion, the new population model is well suited to assess the influence of individual physiological variability on the pharmacokinetics of drugs. It is expected that this new tool can be beneficially applied in the planning of clinical studies.

Objective Rho-kinase activity is increased in cardiovascular disease and in the pathophysiology of hypertension. Few endogenous factors are known that activate the Rho-kinase pathway. Stimulation of P2Y receptors activates the Rho-kinase pathway. Recently identified diguanosine pentaphosphate (Gp(5)G) possibly activates P2Y receptors. In this study, Gp(5)G was identified and quantified in human plasma. The influence of Gp(5)G on vascular tone was studied.Methods Gp(5)G in human plasma was purified to homogeneity by several steps. Gp(5)G was quantified and identified by matrix-assisted laser desorption/ ionization mass spectrometry and enzymatic analysis. The vasoactive effects of Gp(5)G were studied in the isolated perfused rat kidney and after intra-aortic application. Activation of Rho-kinase was measured using western blot analysis.Results The plasma level of Gp(5)G in healthy donors is 9.47 +/- 4.97 nmol/l. Gp(5)G increases contractile responses induced by angiotensin II in a dose-dependent way [ED50 (-log mol) angiotensin II: 10.9 +/- 0.1; angiotensin II plus Gp(5)G (100 nmol/l): 11.5 +/- 0.1]. P-2 receptor antagonists inhibited the Gp(5)G-induced increase in angiotensin II vasoconstriction. MRS2179, a selective P-2Y1 receptor antagonist, had no effect on Gp5G-mediated angiotensin II potentiation. Rho-kinase inhibition by Y27632 abolished the Gp(5)G-induced increase of contractile responses to angiotensin II. Concentrations of 10 nmol/l Gp(5)G activated the translocation of RhoA from the cytosolic to the membranous fraction indicating the activation of Rho-kinase. The intra-aortic application of 100 pmol Gp(5)G significantly increased mean arterial blood pressure by 13.5 +/- 4.2 mmHg.Conclusion Gp(5)G is an endogenous activator of Rho-kinase, which might affect vascular tone control by Rho-kinase at physiological levels. Gp(5)G activates P-2Y4&6 receptors, and might play a role in physiological and pathophysiological vascular tone control.

Objective The adhesion molecules P selectin, E selectin, intercellular adhesion molecule, vascular cellular adhesion molecule (VCAM), and monocyte chemoattractant protein 1 play a important role in the development of arteriosclerotic lesions and are considered main contributors to restenosis after angioplasty. We expected that the serum levels of these markers would increase in the early phase of the first few weeks after angioplasty. Methods We assessed prospectively the levels of soluble forms of adhesion molecules on the day before and then 24 hours and 2 and 4 weeks after angioplasty in arteries of the lower limb by using enzyme-linked immunosorbent assays. We investigated the distribution pattern of these markers in 44 patients (25 male and 19 female; age, 67.7 ± 8.5 years [mean ± SD]) presenting with intermittent claudication (Fontaine stage IIb). Twelve patients (27.3%) underwent diagnostic angiography, 32 (72.2%) received interventional treatment, 22 (68.8%) received balloon angioplasty, and 10 (31.2%) required stent placement. Results Ten (31.3%) of the treated patients developed restenosis within 6 months. These patients had significantly higher levels of P selectin ( P = .034), E selectin ( P = .006), and VCAM ( P = .050) at all time points. E selectin, VCAM, and monocyte chemoattractant protein 1 levels increased between 24 hours and 4 weeks after angiographic procedures, thus indicating that the angiographic procedure itself leads to activation and inflammation of the endothelium. Conclusions This study emphasizes a meaningful role of the adhesion molecules E selectin, P selectin, and VCAM as interesting contributors to restenosis formation after percutaneous transluminal angioplasty.

Purpose: To study the influence of stent size and location on flow patterns in a physiological carotid model. Methods: Wallstents were positioned in silicon models of the carotid artery at various locations: 2 stents appropriately sized to the anatomy were placed in (1) the internal carotid artery (ICA) and (2) the ICA extending completely into the common carotid artery so as to cover the external carotid artery (ECA) orifice. Another 2 stents were placed in the ICA extending (1) partially and (2) completely into the bulb to simulate stent displacement and disproportion between stent size and the original vessel geometry. Measurements were performed with laser Doppler anemometry (LDA) using pulsatile flow conditions (Reynolds number=250; flow 0.431 L/min; ICA:ECA flow rate ratio 70:30) in hemodynamically relevant cross sections. The hemodynamic changes were analyzed with 1-dimensional flow profiles. Results: With the stent in the ICA, no changes of the normal flow profile were seen. For stents positioned in the ICA and extending partially or completely into the carotid bulb, the flow behavior was affected by the resistance of the stent to flow in the ECA. Hemodynamically relevant disturbances were seen in the ICA and ECA, especially in the separation zones (regions along the walls just after a bifurcation, bend, or curve). The ICA:ECA flow rate ratios shifted from 70:30 to 71.3:28.7 and from 70:30 to 75.1:24.9, respectively, in the 2 malpositioned stent models. With the stent placed in the ICA extending completely into the CCA, the ICA:ECA flow rate ratio shifted from 70:30 to 72.4:27.6. In this configuration, there were no notable flow changes in the ICA, but a clear diminishing of the separation zones in the ECA separation zones. Conclusions: Anatomically correct positioning of appropriately sized stents does not lead to relevant flow disturbances in the ICA. In the ECA, depending on the position, size, and interstices of the stent, the physiological flow was considerably disturbed when any part of the stent covered the inflow of the vessel. Disturbances were seen when the stent was positioned into the bulb. For clinical application, stent location and size must be carefully determined so that the stent covers the bifurcation completely or is in the ICA only.

Superior mesenteric artery syndrome (SMAS) is caused by compression of the third part of the duodenum between the superior mesenteric artery and the aorta. It occurs most frequently in patients with rapid weight loss.We report two young patients, who each presented with a longstanding history of postprandial abdominal pain, nausea, and voluminous vomiting. The diagnosis of SMAS was established by digital fluoroscopy and contrast-enhanced spiral computed tomography (CT) scan. The findings obtained by endoscopic ultrasound (EUS) at the site of duodenal compression, using a miniprobe, were of substantial diagnostic value and in good agreement with the radiological observations.Both patients, once diagnosed, were treated conservatively by providing enteral or parenteral high caloric nutrition. Weight gain was accompanied by the complete relief of symptoms.Pathogenesis, diagnostic procedures, and therapy are reviewed in order to draw attention to this rare entity.

The International Agency for Research on Cancer (IARC) has classified high as well as low-frequency fields as "possibly carcinogenic to humans" (Group 2B). For high frequency fields the recent assessment is based mainly on weak positive associations described in some epidemiological studies between glioma and acoustic neuroma and the use of mobile and other wireless phones. Also for lowfrequency fields the evidence is based on epidemiological findings revealing a statistic association between childhood leukemia (CL) and low-level magnetic fields. The basic findings are already 10 years old. They have since been supported by further epidemiological studies. However, the knowledge on the main/crucial question of causality has not improved. This fact and in addition the small, but statistically significant increased incidence of CL in the surrounding of German nuclear power plants have motivated the German Office for Radiation Protection (BfS) to work toward a better understanding of the main causes of CL. A long-term strategic research agenda has been developed which builds on an interdisciplinary, international network and aims at clarifying the aetiology of childhood acute lymphoblastic leukemia.

Hydroxyapatite ceramic made of bovine spongiosa was used as structural support material in a prospective study to correct bone defects experienced after reduction in distal radius fractures. The study took place over a 3-year period (1992-1999) and comprised 14 patients. Osseous integration was analyzed via biopsies and magnetic resonance imaging. Long-term follow-up monitoring involving magnetic resonance imaging in 13 of the 14 patients showed fibrovascular growth within incorporated hydroxyapatite material. Osseous integration was demonstrated in magnetic resonance images by gadolinium uptake and by the presence of osteoid layers and endothelialized vessels. Hydroxyapatite ceramic offers a biologically acceptable alternative to autologous bone when augmenting distal radius fracture fixation.

Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendations to minimise such lapses in communication.

To analyze procedural details, complications and radiation exposure in renal denervation (RDN) using the Medtronic Symplicity® device in the treatment of refractory hypertension.Fifty three consecutive patients underwent RDN. The number of ablations per artery, peri-procedural complications, procedure time (PT), fluoroscopy time (FT), dose-area product (DAP) and procedure-related complications were documented. Additionally, the radiation dose was compared between obese (body mass index ≥ 30 kg/m(2)) and non-obese patients.Bilateral RDN was performed in 50/53 (94 %) cases and with a minimum of 4 ablations per artery in 33/50 (66 %), the mean count being 5.4 (range R: 2 - 13) on the right and 4.3 (R: 1 - 10) on the left. The FT and DAP decreased significantly over the first 12 procedures, reaching a steady state with a median FT of 11.2 min (R: 7.5 - 27) and a median DAP of 4796 cGy × cm(2) (R: 1076 - 21 371), resulting in an effective dose of 15.7 mSv. The median PT was 57 min (R: 40 - 70). Obese patients had a 3.3-fold higher radiation dose (p0.001). We observed one severe spasm and one imminent respiratory depression, both resolved without sequelae.For an experienced interventionalist, RDN has a short learning curve with a low risk profile. The radiation dose does not exceed that of other renal artery interventions, but is explicitly higher in obese patients, who account for a large portion of patients with refractory hypertension.

The adequacy of the UV Index (UVI), a simple measure of ambient solar ultraviolet (UV) radiation, has been questioned on the basis of recent scientific data on the importance of vitamin D for human health, the mutagenic capacity of radiation in the UVA wavelength, and limitations in the behavioral impact of the UVI as a public awareness tool. A working group convened by ICNIRP and WHO met to assess whether modifications of the UVI were warranted and to discuss ways of improving its effectiveness as a guide to healthy sun-protective behavior. A UV Index greater than 3 was confirmed as indicating ambient UV levels at which harmful sun exposure and sunburns could occur and hence as the threshold for promoting preventive messages. There is currently insufficient evidence about the quantitative relationship of sun exposure, vitamin D, and human health to include vitamin D considerations in sun protection recommendations. The role of UVA in sunlight-induced dermal immunosuppression and DNA damage was acknowledged, but the contribution of UVA to skin carcinogenesis could not be quantified precisely. As ambient UVA and UVB levels mostly vary in parallel in real life situations, any minor modification of the UVI weighting function with respect to UVA-induced skin cancer would not be expected to have a significant impact on the UV Index. Though it has been shown that the UV Index can raise awareness of the risk of UV radiation to some extent, the UVI does not appear to change attitudes to sun protection or behavior in the way it is presently used. Changes in the UVI itself were not warranted based on these findings, but rather research testing health behavior models, including the roles of self-efficacy and self-affirmation in relation to intention to use sun protection among different susceptible groups, should be carried out to develop more successful strategies toward improving sun protection behavior.

BACKGROUND Hypertension is a major risk factor for a wide range of cardiovascular diseases and is typically identified by measuring blood pressure (BP) at the brachial artery. Although such a measurement may accurately determine diastolic BP, systolic BP is not reflected accurately. Current noninvasive techniques for assessing central aortic BP require additional recording of an arterial pressure wave using a high-fidelity applanation tonometer. Within one measurement cycle, the Mobil-O-Graph BP device uses brachial oscillometric BP waves for a noninvasive estimation of central BP. We therefore validated the Mobil-O-Graph against the SphygmoCor device, which is widely known as the commonly used approach for a noninvasive estimation of central BP. METHODS For each individual, we compared three readings of the central BP values obtained by the Mobil-O-Graph and SphygmoCor device consecutively. One hundred individuals (mean age 56.1 ± 15.4 years) were recruited for measurement.Differences between the central BP values of the test device and the SphygmoCor device were calculated for each measurement. RESULTS The mean difference (95% confidence interval) for the estimated central systolic BP between both devices was -0.6 ± 3.7 mmHg. Comparison of the central BP values measured by the two devices showed a statistically significant linear correlation (R=0.91, P

PLoS one 6(4), e17626 (2011). doi:10.1371/journal.pone.0017626, Published by PLoS, Lawrence, Kan.

Background Lung cancer is one of the leading causes of death in Europe and the western world. At present, diagnosis of lung cancer very often happens late in the course of the disease since inexpensive, non-invasive and sufficiently sensitive and specific screening methods are not available. Even though the CT diagnostic methods are good, it must be assured that "screening benefit outweighs risk, across all individuals screened, not only those with lung cancer". An early non-invasive diagnosis of lung cancer would improve prognosis and enlarge treatment options. Analysis of exhaled breath would be an ideal diagnostic method, since it is non-invasive and totally painless. Methods Exhaled breath and inhaled room air samples were analyzed using proton transfer reaction mass spectrometry (PTR-MS) and solid phase microextraction with subsequent gas chromatography mass spectrometry (SPME-GCMS). For the PTR-MS measurements, 220 lung cancer patients and 441 healthy volunteers were recruited. For the GCMS measurements, we collected samples from 65 lung cancer patients and 31 healthy volunteers. Lung cancer patients were in different disease stages and under treatment with different regimes. Mixed expiratory and indoor air samples were collected in Tedlar bags, and either analyzed directly by PTR-MS or transferred to glass vials and analyzed by gas chromatography mass spectrometry (GCMS). Only those measurements of compounds were considered, which showed at least a 15% higher concentration in exhaled breath than in indoor air. Compounds related to smoking behavior such as acetonitrile and benzene were not used to differentiate between lung cancer patients and healthy volunteers. Results Isoprene, acetone and methanol are compounds appearing in everybody's exhaled breath. These three main compounds of exhaled breath show slightly lower concentrations in lung cancer patients as compared to healthy volunteers (p < 0.01 for isoprene and acetone, p = 0.011 for methanol; PTR-MS measurements). A comparison of the GCMS-results of 65 lung cancer patients with those of 31 healthy volunteers revealed differences in concentration for more than 50 compounds. Sensitivity for detection of lung cancer patients based on presence of (one of) 4 different compounds not arising in exhaled breath of healthy volunteers was 52% with a specificity of 100%. Using 15 (or 21) different compounds for distinction, sensitivity was 71% (80%) with a specificity of 100%. Potential marker compounds are alcohols, aldehydes, ketones and hydrocarbons. Conclusion GCMS-SPME is a relatively insensitive method. Hence compounds not appearing in exhaled breath of healthy volunteers may be below the limit of detection (LOD). PTR-MS, on the other hand, does not need preconcentration and gives much more reliable quantitative results then GCMS-SPME. The shortcoming of PTR-MS is that it cannot identify compounds with certainty. Hence SPME-GCMS and PTR-MS complement each other, each method having its particular advantages and disadvantages. Exhaled breath analysis is promising to become a future non-invasive lung cancer screening method. In order to proceed towards this goal, precise identification of compounds observed in exhaled breath of lung cancer patients is necessary. Comparison with compounds released from lung cancer cell cultures, and additional information on exhaled breath composition in other cancer forms will be important.

Background Analysis of exhaled breath is a promising diagnostic method. Sampling of exhaled breath is non-invasive and can be performed as often as considered desirable. There are indications that the concentration and presence of certain of volatile compounds in exhaled breath of lung cancer patients is different from concentrations in healthy volunteers. This might lead to a future diagnostic test for lung cancer. Methods Exhaled breath samples from 65 patients with different stages of lung cancer and undergoing different treatment regimes were analysed. Mixed expiratory and indoor air samples were collected. Solid phase microextraction (SPME) with carboxen/polydimethylsiloxane (CAR/PDMS) sorbent was applied. Compounds were analysed by means of gas chromatography (GC) and mass spectrometry (MS). Results The method we used allowed identification with the spectral library of 103 compounds showing at least 15% higher concentration in exhaled breath than in inhaled air. Among those 103 compounds, 84 were confirmed by determination of the retention time using standards based on the respective pure compound. Approximately, one third of the compounds detected were hydrocarbons. We found aromatic hydrocarbons, alcohols, aldehydes, ketones, esters, ethers, sulfur compounds, nitrogen-containing compounds and halogenated compounds. Acetonitrile and benzene were two of 10 compounds which correlated with smoking behaviour. A comparison of results from cancer patients with those of 31 healthy volunteers revealed differences in the concentration and presence of certain compounds. The sensitivity for detection of lung cancer patients based on eight different compounds not seen in exhaled breath of healthy volunteers was 51% and the specificity was 100%. These eight potential markers for detection of lung cancer are 1-propanol, 2-butanone, 3-butyn-2-ol, benzaldehyde, 2-methyl-pentane, 3-methyl-pentane, n-pentane and n-hexane. Conclusions SPME is a relatively insensitive method and compounds not observed in exhaled breath may be present at a concentration lower than LOD. The main achievement of the present work is the validated identification of compounds observed in exhaled breath of lung cancer patients. This identification is indispensible for future work on the biochemical sources of these compounds and their metabolic pathways.

Management of upper gastrointestinal bleeding because of erosion of vessels by esophageal cancer may be challenging. We present herein the angiographic images of a 49-year-old patient who was admitted with massive bleeding from a tumor-eroded inferior thyroid artery. Attempts to control the bleeding by means of flexible endoscopy and insertion of a Sengstaken-Blakemore tube had failed. The diagnosis was impressively demonstrated by multislice computed tomography with intravenous contrast in the arterial phase and multiplanar reconstructions (computed tomography angiography) and by digital subtraction angiography. The bleeding was successfully treated with superselective catheterization and coiling of the eroded vessel.

Objective To investigate transcutaneous oximetry as parameter of the microcirculation is correlated to ankle-brachial-index as parameter of the macrocirculation after peripheral angioplasty procedures. Design Prospective study. Materials and methods 60 patients suffering from intermittent claudication were scheduled for angioplasty treatment. 45 patients were considered as eligible for angioplasty after angiographic evaluation, 15 patients underwent angiography only. Transcutaneous oximetry measurements were performed before the procedure, at the end of intervention, 24 h as well as 2 and 4 weeks after percutaneous transluminal angioplasty. Ankle-brachial-indices were obtained before intervention, 24 h as well as 2 and 4 weeks later. Results Ankle-brachial-indices increased significantly at 24 h after angioplasty in patients being treated with angioplasty. Transcutaneous oximetry values dropped significantly at the end of the procedure and returned close to the baseline levels at 2 and 4 weeks after angioplasty. Ankle-brachial-indices and transcutaneous oximetry were positively correlated before ( r = 0.3833, p = 0.009) as well as 4 weeks after angioplasty ( r = 0.4596, p = 0.001). Immediately after radiological interventions, ankle-brachial-indices and transcutaneous oximetry are not positively correlated. In patients undergoing angiography only, transcutaneous oximetry levels drop significantly immediately after angiography and remain at decreased levels even at 4 weeks after intervention. Conclusion Transcutaneous oximetry as parameter of the microcirculation is positively correlated with ankle-brachial-index as parameter of the macrocirculation before and at 4 weeks after angioplasty. Intraarterial angiography leads to a sudden decrease in skin microcirculation without affecting macrocirculation. As indicated by a lack of recovery in transcutaneous oximetry levels after 4 weeks, angiography alone results in a prolonged impaired microcirculation which may reflect endothelial dysfunction caused by contrast material. The recovery of transcutaneous oximetry levels following angioplasty is counterbalanced by the adverse effects of the contrast material. Ankle-brachial-indices remains the most favourable parameter in evaluating the success of angioplasty procedures while transcutaneous oximetry serves as an indirect method in assessing endothelial dysfunction caused by contrast material.

ObjectivesTo assess prospectively the early time course of Transforming Growth Factor beta-1 (TGFβ-1), basic Fibroblast Growth Factor (bFGF) and Tumor Necrosis Factor alpha (TNFα) as possible contributors to restenosis development after angioplasty.DesignProspective Study.MethodsThe levels of the soluble forms of these factors in the early response to Percutaneous Transluminal Angioplasty (PTA) in the arteries of the lower limb were prospectively assessed. 32 patients with peripheral arterial occlusive disease (PAOD), presenting with intermittent claudication (Fontaine stage IIb) were scheduled for angioplasty treatment. Serum levels of TGFβ-1, TNFα and bFGF were assessed before intervention, 15 and 60 minutes after, 24 hours after as well as 2 and 4 weeks after intervention. We compared the distribution patterns between patients treated with balloon angioplasty and patients who required secondary stent implantation. Endpoint was the development of restenosis within 6 months after interventional treatment, defined as a lumen diameter reduction of more than 50% by ultrasound measurement compared to the result after PTA.ResultsThe patients who later developed restenosis had significantly higher levels of TGFβ-1 at 15 minutes, 24 hours and 2 weeks after PTA (p

To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to the intensive care unit with at least one risk factor for contrast material-induced nephropathy and who receive at least 100 mL of iodinated contrast medium.Institutional ethics review board approval and informed consent were obtained. A total of 91 patients (mean age, 58.5 years+/-14.8 [standard deviation]; 31 women, 60 men; 150 examinations) were admitted to the intensive care unit with at least one risk factor for contrast-induced nephropathy and received either (a) 200 mg theophylline 30 minutes before contrast medium administration (group T), (b) 600 mg acetylcysteine twice daily on the day of and (if possible) the day before the examination (group A), or (c) both agents combined (group AT). The primary endpoint for this study was the incidence of contrast-induced nephropathy (chi2 test).Groups T, A, and AT were comparable with regard to baseline creatinine levels and the amount of contrast medium administered. The incidence of contrast-induced nephropathy in groups T, A, and AT was 2%, 12%, and 4%, respectively, and was significantly lower in group T than in group A (P=.047). There was no significant difference in the incidence of contrast-induced nephropathy between groups A and AT (P=.148) or between groups T and AT (P=.53). For group A, serum creatinine did not change after 12, 24, or 48 hours compared with baseline. Creatinine levels in group T decreased 12 hours (1.19 mg/dL+/-0.58; P=.008) and 48 hours (1.16 mg/dL+/-0.55; P=.034) after contrast material injection compared with baseline (1.25 mg/dL+/-0.61). In group AT, creatinine significantly decreased 24 hours (1.21 mg/dL+/-0.74; P=.003) and 48 hours (1.17 mg/dL+/-0.69; P.001) after contrast material injection compared with baseline (1.28 mg/dL+/-0.74). Group A had significantly higher maximal increases in creatinine than groups T and AT (P=.014).For prophylaxis of contrast-induced nephropathy in patients who are admitted to the intensive care unit and who receive 100 mL or more of contrast medium, theophylline is superior to acetylcysteine.

A 58-year-old woman had massive abdominal bleeding from the splenic artery and the celiac trunk (A) 1 month after pyloruspreserving pancreaticoduodenectomy for duodenal adenoma with high-grade intraepithelial neoplasia. The bleeding was successfully controlled by interventional radiology. The splenic artery was occluded completely with 12 microcoils (A-E; large arrows), and a covered stent was placed into the left gastric artery (A, E, small arrows) by superselective catheterization. The liver received sufficient arterial blood supply from an abberant left liver artery (A, asterisk) arising from the left gastric artery, instead of the usual right liver artery. CT scan shows sufficient perfusion of the liver 9 days after the intervention (F, black asterisks), and shows the gastric artery stent (F, small arrows) and the microcoils (F, large arrows) in the splenic artery. Initially, the arterial perfusion of the liver and stomach appeared sufficient, but the splenic artery was at risk for splenic infarction. Later a 5 5-cm gastric ulcer developed at the lesser curvature, and was managed conservatively. Because of sufficient blood supply through the stented gastric artery, the ulcer healed without perforation. Splenic infarction (F, white asterisk) did occur from the compromised perfusion after occlusion of the splenic artery. The excess fluid surrounding the spleen was managed with interventional CT-controlled drainage (G). Perfusion of the left liver lobe segments II and III appeared diminished (H, asterisk), while the right liver lobe had sufficient blood supply from the portal vein. These complications were negligible compared with the life-threatening bleeding complications, which were successfully controlled. If surgical reintervention had been necessary, gastrectomy and splenectomy would have been the consequence. After full recovery the patient was discharged home from the hospital in fine condition. Six weeks after the procedure, repeat CT-angiography showed good blood flow in the stented left gastric artery and left liver artery. Bleeding from eroded vessels is a frequent complication after pancreatic surgery, especially after radical resection for pancreatic cancer, 8.6% in a series by Rumstadt and coworkers. Vessels in the immediate area are at risk of septic complications, for example the branches of the celiac trunk, which are dissected free during lymphadenectomy. Intestinal contents and pancreatic fluids from anastomotic leakage may cause erosion of vessels or A

In recent years, percutaneous abscess drainage (PAD) of intraabdominal abscesses has become an important tool with regard to the treatment of intraabdominal sepsis. The aim of this study is to assess the value of PAD in the treatment of postoperative retentions. Between 1995 and 1999, the postoperative course of 3346 patients undergoing major abdominal surgery was analyzed. Mortality, morbidity, and comparison of different locations of intraabdominal abscesses were assessed. PAD was considered successful when the patient improved clinically within 24 hours, a decrease in the size of the abscess formation was noted, and complete recovery without further surgical intervention occurred. Out of 3346 operated patients, 174 (5.2%) were diagnosed as having an intraabdominal abscess formation and were treated by PAD. In 63 patients the abscess developed within the upper quadrants, in 66 patients the abscess developed within the lower quadrants, and in the remaining 45 patients the abscess developed within the retroperitoneal cavity or pelvis. The success rate of PAD was 85.6% with a morbidity rate of 4.6%. The least successful location for PAD was the left upper quadrant. Patients with abscess drainage in the right upper and lower quadrant experienced a high success rate. One patient died due to the PAD procedure. Unsuccessful PAD was closely related to an increase in mortality. In the case of intraabdominal abscess formation after visceral surgery, PAD should be the primary procedure. Attention should be paid to abscess formations in the left upper quadrant because there is an increased likelihood of complications caused by PAD.

Totally implantable venous access ports (TIVAPs) provide a useful option for intravenous parenteral feeding and application of chemotherapy in patients with malignancies. 1 The use of long-term catheters was first described by Broviac et al 2 in 1973 and later modified by Hickman et al 3 in 1979. In 1982, Niederhuber et al 4 introduced totally implanted venous port systems for patients with cancer. The mean duration that catheters are left in place is about 12 months. 1 , 5 Complications after implantation of TIVAPs are rare 6 , 7 and depend on the disease, the patient's performance status and blood cell count, the technique for placement of the catheter and port reservoir, and the postoperative care.8 They can be categorized as early and late complications. Early complications include pneumothorax, infections, bleeding, wound-healing disorders, pulmonary distress, and dislocation. Late complications include infections, abscesses, sepsis, and thrombosis or secondary leakages. A TIVAP catheter leakage can be related to inadequacies in the surgical technique or faults in the material and can lead to extravasation injury. 9 The diagnosis is made clinically, radiologically, or by both means. We report a case in which noninvasive sonography in the power Doppler mode was used with 0.9% sodium chloride as a contrast medium to provide evidence of a TIVAP catheter leakage. From this experience, noninvasive sonography in the power Doppler mode and 0.9% sodium chloride as a contrast agent might be a useful tool for diagnosis of leakage in a port system.

To study the influence of a newly developed membrane stent design on flow patterns in a physiologic carotid artery model. Three different stents were positioned in silicone models of the carotid artery: a stainless steel stent (Wall-stent), a nitinol stent (SelfX), and a nitinol stent with a semipermeable membrane (MembraX). To increase the contact area of the membrane with the vessel wall, another MembranX model was modified at the outflow tract. The membrane consists of a biocompatible silicone-polyurethane copolymer (Elast-Eon) with a pore size of 100 μm. All stents were deployed across the bifurcation and the external carotid artery origin. Flow velocity measurements were performed with laser Doppler anemometry (LDA), using pulsatile flow conditions (Re = 220; flow 0.39 l/min; flow rate ratio ICA:ECA = 70:30) in hemodynamically relevant cross-sections. The hemodynamic changes were analyzed by comparing velocity fluctuations of corresponding flow profiles. The flow rate ratio ICA:ECA shifted significantly from 70/30 to 73.9/26.1 in the MembraX and remained nearly unchanged in the SelfX and Wallstent. There were no changes in the flow patterns at the inflow proximal to the stents. In the stent no relevant changes were found in the SelfX. In the Wallstent the separation zone shifted from the orifice of the ICA to the distal end of the stent. Four millimeters distal to the SelfX and the Wallstent the flow profile returned to normal. In the MembraX an increase in the central slipstreams was found with creation of a flow separation distal to the stent. With a modification of the membrane this flow separation vanished. In the ECA flow disturbances were seen at the inner wall distal to the stent struts in the SelfX and the Wallstent. With the MembraX a calming of flow could be observed in the ECA with a slight loss of flow volume. Stent placement across the carotid artery bifurcation induces alterations of the physiologic flow behavior. Depending on the stent design the flow alterations are located in different regions. All the stents tested were suitable for the carotid bifurcation. The MembraX prototype has shown promising hemodynamic properties ex vivo.

Background and Purpose— Embolic events are a major cause for procedure-related strokes after carotid endarterectomy (CEA). Transcranial Doppler sonography can reveal embolic events as microembolic signals (MES) during CEA. MES during declamping and shunting are frequently detected. MES during shunting are rare and known to be correlated with the neurological outcome of the patient. In the present study, we analyzed the occurrence of MES within different stages of CEA and whether MES within those stages were correlated with cerebral ischemia, as detected by diffusion-weighted imaging (DWI), and brain infarction, as detected by contrast-enhanced MRI. Methods— Thirty-three patients were monitored intraoperatively for MES using transcranial Doppler sonography. DWI was performed within 24 hours before and after surgery. Positive postoperative DWI led to reexamination with contrast-enhanced T1-MRI 7 to 10 days after CEA for detection of cerebral infarction. Results— MES were detected in 32 of 33 patients. The highest number of MES was found during shunting and declamping. A significant correlation was found between MES and DWI-lesions during dissection. A significant correlation was found between MES during dissection and shunting, and nonsignificant correlation was found between MES and the occurrence of cerebral infarction. Conclusion— MES could be regularly detected during CEA. Dissection and shunting seem to be the most vulnerable stages of the procedure.

THE UVI working group acknowledges the contribution of Vitamin D to bone health as stated in our paper. However, we concluded that an optimal level of Vitamin D for humans has not yet been established with any certainty...

Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a. To evaluate the impact of SERCA2a overexpression on SR Ca2+ handling in diabetic CM, we 1) generated transgenic rats harboring a human cytomegalovirus enhancer/chicken beta-actin promotor-controlled rat SERCA2 transgene (SERCA2-TGR), 2) characterized their SR phenotype, and 3) examined whether transgene expression may rescue SR Ca2+ transport in streptozotocin-induced diabetes. The transgene was expressed in all heart chambers. Compared to wild-type (WT) rats, a heterozygous line exhibited increased SERCA2 mRNA (1.5-fold), SERCA2 protein (+26%) and SR Ca2+ uptake (+37%). Phospholamban expression was not altered. In SERCA2-TGR, contraction amplitude (+48%) and rates of contraction (+34%) and relaxation (+35%) of isolated papillary muscles (PM) were increased (P2+ uptake and SERCA2 protein of SERCA2-TGR were 1.3-fold higher (P2+ uptake, accelerates relaxation and compensates, in part, for depressed Ca2+ uptake in diabetic CM. Therefore, SERCA2 expression might constitute an important therapeutic target to rescue cardiac SR Ca2+ handling in diabetes.

Objective: To investigate whether the adenosine-antagonist theophylline reduces the incidence of contrast-induced nephropathy (CIN). Design and setting: Prospective, comparison to series of patients at similar risk of CIN in a university hospital medical ICU. Patients: 78 ICU patients with at least one risk factor for CIN undergoing 150 consecutive contrast examinations. Interventions: Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that of 100 ml or more low-osmolarity contrast medium (CM). Measurements and results: Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume, fluid balance, and the incidence of CIN [increase in creatinine ≥0.5 mg/dl (=44.2 µmol/l) within 48 h] were monitored for 48 h. Despite the large number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml), impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin (53%), catecholamines (52%), creatinine concentrations were not increased 24 h (1.40±0.92 mg/dl) or 48 h (1.38±0.88 mg/dl) after CM [1.47±1.0 mg/dl (=130±88 µmol/l)] vs. baseline. The fluid balance was not different before (+3 ml/h) and after CM (–9 ml/h). The urine volume slightly increased after CM and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN. The incidence was significantly lower than that of 14% (78/565) in the control series with patients at comparable risk of CIN (p