Low-dose 5-fluorouracil in combination with salicylic acid for the treatment of actinic keratoses on the hands and/or forearms - results of a non-interventional study.

BACKGROUND: As an in situ carcinoma, actinic keratoses should be treated early. Previous studies on the efficacy of a low-dose 0.5% 5-fluorouracil solution in combination with 10% salicylic acid (low-dose 5-FU/SA) are mostly related to lesions appearing on the head and face. In contrast, actinic keratoses (AK) lesions of the upper extremities are considered to be difficult to treat. OBJECTIVE: The efficacy of low-dose 5-FU/SA in the treatment of actinic keratoses on the hands and/or forearms was studied for the first time in this non-interventional study (NIS) under practical conditions in a large patient population. In addition to the clinical course during therapy and a follow-up period, the length of application and adherence were documented. METHODS: As part of this NIS, 649 patients with AK were treated at 207 centres with low-dose 5-FU/SA. The data of the study were recorded at baseline, optionally during an intermediate examination, at the end of therapy and during a final assessment. RESULTS: The average number of AK lesions decreased during the entire observation period by 92%. Side-effects were documented only rarely in the form of local skin reactions (2%). The attending physicians assessed the efficacy, tolerability and safety of the therapy as being predominantly very good or good (in each case ≥90%). CONCLUSION: AK lesions on the hands and/or forearms were effectively treated with low-dose 5-FU/SA under routine conditions in dermatological practice and the treatment was well tolerated.

Combined indocyanine green and quantitative perfusion assessment with hyperspectral imaging during colorectal resections.

Anastomotic insufficiencies still represent one of the most severe complications in colorectal surgery. Since tissue perfusion highly affects anastomotic healing, its objective assessment is an unmet clinical need. Indocyanine green-based fluorescence angiography (ICG-FA) and hyperspectral imaging (HSI) have received great interest in recent years but surgeons have to decide between both techniques. For the first time, two data processing pipelines capable of reconstructing an ICG-FA correlating signal from hyperspectral data were developed. Results were technically evaluated and compared to ground truth data obtained during colorectal resections. In 87% of 46 data sets, the reconstructed images resembled the ground truth data. The combined applicability of ICG-FA and HSI within one imaging system might provide supportive and complementary information about tissue vascularization, shorten surgery time, and reduce perioperative mortality.

Towards trends in minimal invasive cardiac surgery.

While various minimally invasive techniques have been established in many other surgical specialties during the last decades, cardiac surgery has been one of the last domains to adopt the principles of minimally invasive techniques. This was mainly based on the reduced surgical exposure in highly complex cardiac operations and the missing technical requirements in the beginning of the modern cardiac era. Nowadays, technical conditions have continuously improved and have become routine also in cardiac surgery. Most of these novel minimal-invasive concepts have been developed in order to treat high-risk or inoperable patients by reducing operative trauma. Actually, since more high-risk and multimorbid patients were referred for surgery, these initial extraordinary procedures have been adopted into daily clinical routine. Currently, many promising innovations aim to reduce the operative trauma and perioperative morbidity, and furthermore, to increase patients' satisfaction and security. It is anticipated that in the future this current trend towards minimal invasiveness will increase further due to an increased demand, and therefore, such minimal-invasive procedures will become less complex and straightforward.

[Principles of MR-guided interventions, surgery, navigation, and robotics]. / Prinzipien Magnet-Resonanz-geführter Intervention, Operation, Navigation und Robotik.

The application of magnetic resonance imaging (MRI) as an imaging technique in interventional and surgical techniques provides a new dimension of soft tissue-oriented precise procedures without exposure to ionizing radiation and nephrotoxic allergenic, iodine-containing contrast agents. The technical capabilities of MRI in combination with interventional devices and systems, navigation, and robotics are discussed.

[Possibilities and perspectives of hyperspectral imaging in visceral surgery]. / Möglichkeiten und Perspektiven der Hyperspektralbildgebung in der Viszeralchirurgie.

HyperSpectral Imaging (HSI) technology enables quantitative tissue analyses beyond the limitations of the human eye. Thus, it serves as a new diagnostic tool for optical properties of diverse tissues. In contrast to other intraoperative imaging methods, HSI is contactless, noninvasive, and the administration of a contrast medium is not necessary. The duration of measurements takes only a few seconds and the surgical procedure is only marginally disturbed. Preliminary HSI applications in visceral surgery are promising with the potential of optimized outcomes. Current concepts, possibilities and new perspectives regarding HSI technology together with its limitations are discussed in this article.

[Eosinophilic fasciitis and asplenia]. / Eosinophile Fasziitis und Asplenie.

Eosinophilic fasciitis (Shulman syndrome) is a chronic inflammation primarily of the septums and fascia, and is characterized by the infiltration of eosinophils with additional similarities to systemic sclerosis. Several diseases have been described in association with eosinophilic fasciitis. Among these are aplastic anaemia, haemolytic anaemia, thrombocytopenia, lymphoproliferative disorders, thyroiditis, pulmonary fibrosis, Sjögren's syndrome, Raynaud's phenomenon, myositis, medium vessel vasculitis, pericarditis, colitis and glomerulonephritis. To date, no association with congenital asplenia has been described. We report the case of a woman with eosinophilic fasciitis and congenital asplenia and discuss the possible causes and potential consequences.

Obliquely propagating dust-density waves.

Self-excited dust-density waves are experimentally studied in a dusty plasma under microgravity. Two types of waves are observed: a mode inside the dust volume propagating in the direction of the ion flow and another mode propagating obliquely at the boundary between the dusty plasma and the space charge sheath. The dominance of oblique modes can be described in the frame of a fluid model. It is shown that the results fom the fluid model agree remarkably well with a kinetic electrostatic model of Rosenberg [J. Vac. Sci. Technol. A 14, 631 (1996)]. In the experiment, the instability is quenched by increasing the gas pressure or decreasing the dust density. The critical pressure and dust density are well described by the models.

Probability of metastable configurations in spherical three-dimensional Yukawa crystals.

Recently the occurrence probabilities of ground and metastable states of three-dimensional Yukawa clusters with 27 and 31 particles have been analyzed in dusty plasma experiments [D. Block, Phys. Plasmas 15, 040701 (2008)]. There it was found that, in many cases, the ground state appeared substantially less frequently than excited states. Here we analyze this question theoretically by means of molecular dynamics (MD) and Monte Carlo simulations and an analytical method based on the canonical partition function. We confirm that metastable states can occur with a significantly higher probability than the ground state. The results strongly depend on the screening parameter of the Yukawa interaction and the damping coefficient used in the MD simulations. The analytical method allows one to gain insight into the mechanisms being responsible for the occurrence probabilities of metastable states in strongly correlated finite systems.

[Hyperspectral imaging of gastrointestinal anastomoses]. / Hyperspektral-Imaging bei gastrointestinalen Anastomosen.

INTRODUCTION: Anastomotic insufficiency (AI) remains the most feared surgical complication in gastrointestinal surgery, which is closely associated with a prolonged inpatient hospital stay and significant postoperative mortality. Hyperspectral imaging (HSI) is a relatively new medical imaging procedure which has proven to be promising in tissue identification as well as in the analysis of tissue oxygenation and water content. Until now, no data exist on the in vivo HSI analysis of gastrointestinal anastomoses. METHODS: Intraoperative images were obtained using the TIVITA™ tissue system HSI camera from Diaspective Vision GmbH (Pepelow, Germany). In 47 patients who underwent gastrointestinal surgery with esophageal, gastric, pancreatic, small bowel or colorectal anastomoses, 97 assessable recordings were generated. Parameters obtained at the sites of the anastomoses included tissue oxygenation (StO2), the tissue hemoglobin index (THI), near-infrared (NIR) perfusion index, and tissue water index (TWI). RESULTS: Obtaining and analyzing the intraoperative images with this non-invasive imaging system proved practicable and delivered good results on a consistent basis. A NIR gradient along and across the anastomosis was observed and, furthermore, analysis of the tissue water and oxygenation content showed specific changes at the site of anastomosis. CONCLUSION: The HSI method provides a non-contact, non-invasive, intraoperative imaging procedure without the use of a contrast medium, which enables a real-time analysis of physiological anastomotic parameters, which may contribute to determine the "ideal" anastomotic region. In light of this, the establishment of this methodology in the field of visceral surgery, enabling the generation of normal or cut off values for different gastrointestinal anastomotic types, is an obvious necessity.

In vivo validation of spatio-temporal liver motion prediction from motion tracked on MR thermometry images.

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) of the liver during free-breathing requires spatio-temporal prediction of the liver motion from partial motion observations. The study purpose is to evaluate the prediction accuracy for a realistic MRgFUS therapy scenario, namely for human in vivo data, tracking based on MR images routinely acquired during MRgFUS and in vivo deformations caused by the FUS probe. METHODS: In vivo validation of the motion model was based on a 3D breath-hold image and an interleaved acquisition of two MR slices. Prediction accuracy was determined with respect to manually annotated landmarks. A statistical population liver motion model was used for predicting the liver motion for not tracked regions. This model was individualized by mapping it to end-exhale 3D breath-hold images. Spatial correspondence between tracking and model positions was established by affine 3D-to-2D image registration. For spatio-temporal prediction, MR tracking results were temporally extrapolated. RESULTS: Performance was evaluated for 10 volunteers, of which 5 had a dummy FUS probe put on their abdomen. MR tracking had a mean (95 %) accuracy of 1.1 (2.4) mm. The motion of the liver on the evaluation MR slice was spatio-temporally predicted with an accuracy of 1.9 (4.4) mm for a latency of 216 ms. A simple translation model performed similarly (2.1 (4.8) mm) as the two MR slices were relatively close (mean 38 mm). Temporal prediction was important (10 % error reduction), while registration effects could only partially be assessed and showed no benefits. On average, motion magnitude, motion amplitude and breathing frequency increased by 24, 16 and 8 %, respectively, for the cases with FUS probe placement. This motion increase could be reduced by the spatio-temporal prediction. CONCLUSION: The study shows that tracking liver vessels on MR images, which are also used for MR thermometry, is a viable approach.

Presentation of a kindred with familial medullary thyroid carcinoma and Cys611Phe mutation of the RET proto-oncogene demonstrating low grade malignancy.

OBJECTIVE: Both multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are caused by germline mutations of the RET proto-oncogene. A broad spectrum of malignancy within and between families has been described with no clear genotype-phenotype correlation due to a scarcity of available data of large kindreds. DESIGN: Here we present the only known family with a germline mutation of codon 611 TGC to TTC (exon 10) in the RET proto-oncogene leading to a replacement of cysteine by phenylalanine (Cys611Phe or C611F). RESULTS: Twenty family members of this large kindred are gene carriers (GCs) and seven (5-13 years old) are potential carriers but have yet to be analysed. The clinical course of medullary thyroid carcinoma (MTC) in this family is characterized by a very slow evolution and progression of the tumour with no MTC-related death to date. Of 11 patients (30-69 years old) having undergone thyroidectomy six were classified as pT1, four as pT2 and one as C-cell hyperplasia according to the TNM system of the International Union Against Cancer. Due to cervical and mediastinal lymph node metastasis one patient (44 years old) had to be operated on a second time. The seven non-operated GCs of the fourth and fifth generation (17-26 years old) are yearly monitored with pentagastrin stimulation tests; one non-operated GC (43 years old) has refused any further investigations. Screening for primary hyperparathyroidism and phaeochromocytoma was negative in all cases. CONCLUSION: We suggest from these experiences that the general advice for thyroidectomy in early childhood should be modified in certain families, depending on genotype.

The active magnetic resonance imaging stent (AMRIS): initial experimental in vivo results with locally amplified MR angiography and flow measurements.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) is limited by artifacts in vessels after stenting. An active MR imaging stent (AMRIS) allows for artifact-free imaging with local improvement in signal-to-noise ratio (SNR). In a rabbit model, we evaluated the imaging properties by MR angiography (MRA) and flow measurements. METHODS: The AMRIS was placed in the abdominal aorta of five rabbits. At 1.5 T, MRA (three-dimensional fast low-angle shot) was performed before and after intravenous injection of an iron oxide-based, blood-pool contrast medium (dose, 50 micromol Fe/kg), and flow measurements were performed (electrocardiographically triggered phase-contrast cine gradient-echo sequence). Mean SNRs were calculated and flow volume curves were generated. RESULTS: The SNR was 6.0 +/- 0.6 (outside the stent) versus 12.3 +/- 1.1 (inside the stent, P < 0.05) for plain MRA, 21.2 +/- 0.6 versus 40.6 +/- 5.2 (P < 0.05) for contrast-enhanced MRA, and 5.4 +/- 0.4 versus 13.7 +/- 2.1 (P < 0.05) for the magnitude images of flow measurements. Flow volume curves within and distal to the stent were comparable. CONCLUSIONS: By using the AMRIS as a vascular stent, the stented vessel segment can be examined with enhanced signal intensity on MRI.

Effect of increased protein intake and nutritional status on whole-body protein metabolism of AIDS patients with weight loss.

The aim of this study was to investigate nutritional status and protein metabolism during total parenteral nutrition (TPN) in AIDS patients with weight loss. Six patients on treatment for AIDS-associated complications were investigated and reviewed TPN that supplied energy equivalent to 1.5 times the resting energy expenditure (REE). Amino acid (AA) supply increased from 0.6 g/kg body weight (BW)/d on days 1 to 3 and 1.2 on days 4 to 6 to 1.8 on days 7 to 9. Nonprotein energy was given as equicaloric amounts of glucose and fat emulsion. There were repeated measurements of nitrogen balance and whole-body protein turnover (WBPT) using a bolus 15N-glycine method on the morning of days 3, 6, and 9. Principal findings were as follows: (1) increasing the supply of AAs significantly improves nitrogen balance in AIDS patients; (2) there is no simple linear effect of increasing amounts of AAs on WBPT in AIDS patients; (3) WBPT is high and variable in these patients; and (4) mean WBPT of each patient is significantly correlated with body cell mass (BCM) as a proportion of BW (P < .001, r = .92). We conclude that poor nutritional status in AIDS patients with weight loss is associated with high WBPT. However, these patients can attain at least transiently positive nitrogen balance with sufficient protein intake, predominantly through an increase in whole-body protein synthesis (WBPS).

Heavy metal accumulation (lead and cadmium) and ion exchange in three species of Sphagnaceae : I. Main principles of heavy metal accumulation in Sphagnaceae.

Three different species of Sphagnum mosses originating from a bog ("Hochmoor") were examined with respect to their behaviour of accumulation of heavy metal ions lead and cadmium. A strong bond of double charged Pb could be found independent of the Sphagnum species. When competitive reactions were performed in test solutions, with two ions (Pb2+ and one alkali or one earthalkali ion) or three (Pb2+ and one earthalkali and one alkali ion) Pb2+ was always accumulated too. This leads to a suppression of exchange of the other ions. Cadmium is by far less strongly bound than lead. Cadmium was tested in combination with two or three ions as was done for lead. The behaviour of cadmium adsorption is similar to that of calcium. For a number of ions typical tendencies were observed, which give insight in the quantity and strength of their binding to the exchanging material. The following series of accumulation was found: Pb2+>Cd2+≥Ca2+>Mg2+>K+>Na+≥NH inf4sup+ . (Accumulation was determined in test solutions containing each ion in the concentration 0.01N.) Differences in this series selectivity could not be found within the three Sphagnum species. But there exist typical differences in the total amount of adsorbed ions per unit dry weight. This species specific value corresponds with total capacities for ion exchange of the three species. Furthermore acid strength as well as pH-dependence of the ion exchanging Sphagnum material were investigated. Its physico-chemical behaviour may be described as that of a weak acid polyelectrolyte with variable charge, depending on ionic strength.

Heavy metal accumulation (lead and cadmium) and ion exchange in three species of Sphagnaceae : II. Chemical equilibrium of ion exchange and the selectivity of single ions.

Chemical equilibrium of ion exchange reactions of Sphagnum mosses was investigated for four different combinations of ions. These combinations were: Pb/Ca; Cd/Ca; Pb/K; Cd/K. Based on the law of mass action one can find mathematical descriptions of ion exchange reactions which permit one to calculate a state of equilibrium. As a measure of ion selectivity a rational coefficient of selectivity can be used. For culture experiments three different species of Sphagnum originating from a bog ("Hochmoor") in southern Bavaria were used. With these species coefficients of selectivity of the mentioned heavy metals were determined in solutions of different total ion content. Furthermore for each test solution of fixed total concentration the portions of the ions were altered. The Sphagnum material shows the behaviour of a relative ideal ion exchanger, whose states of equilibrium can be well described by the mathematical equations. The coefficients of selectivity are independent of Sphagnum species. In all cases they reflect the preferred binding of lead to the exchanger. Cadmium and calcium are adsorbed in approximately equivalent amounts. Representative limit isotherms permit an estimation of the errors caused by variation of the rational coefficients of selectivity. The applicability of the determined interactions and regularities on heavy metal monitoring programs is discussed.

Seasonal variations in nitrate content, total nitrogen, and nitrate reductase activities of macrophytes from a chalk stream in Upper Bavaria.

11 macrophytic species from a groundwater influenced chalk stream in Upper Bavaria were investigated during a period of one year in order to determine differences in the endogenous nitrate content, in total nitrogen content and in nitrate reductase activity (NRA). Nitrate concentrations of different plants taken from the same site of the river varied by a factor of approximately 103. A maximum of 1,958 µmol NO 3- g-1 dry w. could be measured in the petioles of Nasturtium officinale, which accounts for 12% of plant dry w. Very high values were also found in Callitriche obtusangula and Veronica angallis-aquatica. In comparison to the ambient water, mean accumulation rates of up to 131 could be found. In Fontinalis antipyretica, the plant poorest in nitrate, the ratio was only 1.24:1. Elodea canadensis belonged to a group of plants having very low nitrate concentrations. Since NRA was very low too, it is assumed that nitrogen nutrition of this species depends rather on ammonia than on nitrate. With a few exceptions nitrate content of different plant organs varied markedly. In general they were lowest in leaves and highest in shoot axes. Appreciable amounts of nitrate were also found in the roots of plants. No correlation could be found between endogenous nitrate content and NRA. In contrast to endogenous nitrate content and NRA, total nitrogen concentrations of the plants did not differ significantly.

Nitrate content and nitrate reductase activity in Rumex obtusifolius L. : I. Differences in organs and diurnal changes.

With Rumex obtusifolius L., the influence of some environmental conditions on nitrate uptake and reduction were investigated. Nitrate concentrations of plant material were determined by HPLC, the activity of nitrate reductase by an "in vivo" test. As optimal incubation medium, a buffer containing 0.04 M KNO3; 0.25 M KH2PO4; 1.5% propanol (v/v); pH 8.0 was found. Vacuum infiltration caused an increase of enzyme activity of up to 40%.High nitrate concentrations were found in roots and leaf petioles. Nitrate reductase activity of these organs, however, was low. On the other hand, the highest nitrate reductase activity was observed in leaf laminae, which contained lowest nitrate concentrations.In leaves, nitrate content and nitrate reductase activity exhibited inverse diurnal fluctuations. During darkness, decreasing activities of the enzyme were followed by increasing nitrate concentrations, while during light the contrary was true. In petioles diurnal fluctuations in nitrate content were observed, too. No significant correlations with illumination, however, could be found.Our results prove that Rumex obtusifolius is characterized by an intensive nitrate turnover. Theoretically, internal nitrate content of the plant would be exhausted within a few hours, if a supply via the roots would be excluded.

Nitrate content and nitrate reductase activity in Rumex obtusifolius L. : II. Responses to nitrate starvation and nitrogen fertilization.

The aim of this work was to investigate the effect of nitrogen starvation and subsequent fentilization with nitrate or ammonium on nitrate content and nitrate reductase activity of Rumex obtusifolius L. under natural conditions.When plants were transplanted to nitrate-poor media, endogenous nitrate was reduced within a few days. In parallel, nitrage reductase activities dropped to about 25% of the initial values. As a consequence of nitrate fertilization (1; 10 or 100 mmol KNO3/l substrate), endogenous nitrate content of the plant abruptly increased within one day. In extreme cases, nitrate concentrations of up to 10% of plant dry weight could be observed without being lethal. High external nitrate concentrations caused an inhibition of nitrate reductase within the leaves, while low external concentrations provoked an increase in the enzyme activity of about 450% within one day. Ammonium fertilization (5 mmol (NH4)2SO4/l substrate) also caused an increase in nitrate reductase activity and nitrate content within leaf blades. This observation indicates a rapid nitrification of ammonium in the substrate. When plants were fertilized with ammonium plus nitrate (2.5 mmol (NH4)2SO4+ 5 mmol KNO3/l substrate), an extremely high and long term increase in nitrate reduction could be observed. Due to an intensive enzymatic nitrate turnover, the nitrate content of leaf blades then remained relatively low. Our observations do not point to an inhibition of nitrate reductase activity in leaves of Rumex obtusifolius by ammonium. Despite temporarily high endogenous nitrate concentrations, Rumex obtusifolius may not be termed as a "nitrate storage" plant, since the accumulation of nitrate is a short term process only.

Mode spectra of thermally excited two-dimensional dust Coulomb clusters.

The mode spectra of finite Coulomb clusters, confined systems of charged microspheres in a complex plasma, have been determined experimentally. The spectral power density of all possible modes has been measured for particle numbers between N=3 and N=145 under different plasma conditions. The agreement between measured and calculated mode frequencies is found to be very good. From this, the parameters of the particle interaction, like particle charge and screening strength, have been extracted quantitatively. In addition, the particle and mode temperatures have been obtained. The modes and the particles show the same temperature and the principle of equipartitition holds for these systems. Moreover, certain modes of interest have been compared among the different clusters, as there are the breathing mode and intershell rotation as well as the lowest- and highest-frequency modes. Moreover, the mode-integrated spectrum shows two broad maxima which are explained from "shearlike" or "compressionlike" modes. From this analysis, the transition from finite number to crystal-like properties is observed to occur around N=12 particles. Finally, a model to visualize the transition from normal mode oscillations to wave dispersions in a 2D lattice has been proposed.

Nonlinear resonances of particles in a dusty plasma sheath.

Vertical oscillations of microparticles trapped in the sheath of a capacitive rf discharge have been excited showing a strongly nonlinear resonance. The nonlinear oscillations are analyzed in terms of an anharmonic fourth-order potential energy curve. It is demonstrated that the observed nonlinearities can be related to a position dependent charge of the microspheres, whereas the electric field is found to be as nearly linearly increasing. The experimental results on the position dependent charging and electric field structure are compared to a numerical model.