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In September 2014, the Rockefeller Brothers Fund (RBF) announced its decision to divest from fossil fuels, the original source of the foundation’s endowment. The 800 individual and institutional investors who took the Divest-Invest pledge in September 2014 controlled, at the time, $50 billion in assets. Today, nearly 60,000 individuals and over 1,000 institutional investors with combined assets exceeding $12 trillion have pledged to partially or fully divest from fossil fuels. In this chapter, RBF President and CEO Stephen B. Heintz traces the brief history of the divestment movement - a history marked by extraordinary success. Through the RBF’s own story, Heintz lays out the moral and economic case for divestment from fossil fuels and investment in the clean energy solutions of the future. Investors have an important role to play in the ecological and economic transition that the climate crisis demands. The time for them to act is now.

Microbial community compositions and functional profiles were analyzed in microcosms established using aquifer materials from a former automobile factory site, where 1,4-dioxane was identified as the primary contaminant of concern. Propane or oxygen biostimulation resulted in limited 1,4-dioxane degradation, which was markedly enhanced with the addition of nutrients, resulting in abundant Mycobacterium and Methyloversatilis taxa and high expressions of propane monooxygenase gene, prmA. In bioaugmented treatments, Pseudonocardia dioxanivorans CB1190 or Rhodococcus ruber ENV425 strains dominated immediately after augmentation and degraded 1,4-dioxane rapidly which was consistent with increased representation of xenobiotic and lipid metabolism-related functions. Although the bioaugmented microbes decreased due to insufficient growth substrates and microbial competition, they did continue to degrade 1,4-dioxane, presumably by indigenous propanotrophic and heterotrophic bacteria, inducing similar community structures across bioaugmentation conditions. In various treatments, functional redundancy acted as buffer capacity to ensure a stable microbiome, drove the restoration of the structure and microbial functions to original levels, and induced the decoupling between basic metabolic functions and taxonomy. The results of this study provided valuable information for design and decision-making for ex-situ bioreactors and in-situ bioremediation applications. A metagenomics-based understanding of the treatment process will enable efficient and accurate adjustments when encountering unexpected issues in bioremediation.

©2015. American Geophysical Union. We report methane (CH 4 ) concentration and methane oxidation (MO x ) rate measurements from the eastern tropical north Pacific (ETNP) water column. This region comprises low-CH 4 waters and a depth interval (~200-760m) of CH 4 supersaturation that is located within a regional oxygen minimum zone (OMZ). MO x rate measurements were made in parallel using tracer-based methods with low-level 14C-CH 4 (LL 14C) and 3H-CH 4 (3H). The two tracers showed similar trends in MO x rate with water depth, but consistent with previous work, the LL 14C rates (range: 0.034-15×10-3nmol CH 4 L-1d-1) were systematically slower than the parallel 3H rates (range: 0.098-4000×10-3nmol CH 4 L-1d-1). Priming and background effects associated with the 3H-CH 4 tracer and LL 14C filtering effects are implicated as the cause of the systematic difference. The MO x rates reported here include some of the slowest rates measured in the ocean to date, are the first rates for the ETNP region, and show zones of slow CH 4 turnover within the OMZ that may permit CH 4 derived from coastal sediments to travel great lateral distances. The MO x rate constants correlate with both CH 4 and oxygen concentrations, suggesting that their combined availability regulates MO x rates in the region. Depth-integrated MO x rates provide an upper limit on the magnitude of regional CH 4 sources and demonstrate the importance of water column MO x , even at slow rates, as a sink for CH 4 that limits the ocean-atmosphere CH 4 flux in the ETNP region.

Methane concentrations and turnover rates were measured throughout the water column at nine stations in the Santa Monica Basin (SMB), at one station in the San Pedro Basin (SPB), and at one station in the Santa Catalina Basin (SCtB) in July 2007 and September 2009. Methane concentrations were elevated throughout the water column, with subsurface (4–15 nmol L−1), midwater (7.5–100 nmol L−1), and bottom-water (5–242 nmol L−1) maxima. The SMB water column was divided into four depth-dependent regimes, based on temperature-salinity relationships and patterns in methane concentration and fractional turnover rate. We propose that distinct physical controls on methane dynamics distinguish these regimes. In the upper water column, methanotrophic activity appears to be controlled by borderland-scale, seasonal fluctuations in circulation. The midwaters represent a transition regime between northern-sourced shallow waters and southern-sourced deep waters, wherein methanotrophic activity decreases with depth to its minimum at 500 m, coinciding with the midwater methane maxima. Below 500 m, methanotrophic activity increases to the sill depth of 737 m, coincident with increasingly restricted circulation of water. Bottom waters are restricted from through-basin circulation. These waters were oxygen depleted, but methane input sustained an active psychrotolerant methanotrophic community and had some of the fastest aerobic methane oxidation rates yet reported in the marine environment.

Methane (CH 4 ) emitted into the coastal ocean faces two primary fates: escape to the atmosphere or prolonged dissolution that allows sufficient time for oxidation by methanotrophic bacteria. The partitioning of CH 4 between these fates is modulated by physical, chemical and biological factors, including the distribution of CH 4 in the water, temperature, wind speed, water movement, and the biological CH 4 oxidation rate. Because of the underlying complexity, studies rarely quantify all of these factors in unison, thereby leaving gaps in our understanding of CH 4 biogeochemistry in the coastal ocean. In this study we estimated the partitioning of CH 4 between transport, microbial oxidative loss, and sea–air transfer in a defined plume of dissolved CH 4 originating from one of the world's largest seep fields, near Coal Oil Point (COP) in the Santa Barbara Channel, California. Depth distributions of CH 4 concentration, biologically mediated oxidation rate, and current velocity were quantified at 12 stations in a 198 km 2 area down-current from COP on July 4–5, 2007. Six stations were sampled again on July 7, 2007 to evaluate temporal plume variability. The observed CH 4 distribution revealed two distinct CH 4 plumes: a shallow plume centered at ∼40 m and a deeper plume centered at ∼200 m. The shallow plume originates at COP; the source of the deeper CH 4 plume is not known. Cross-sections of both plumes were used to calculate transport and loss terms for dissolved CH 4 . The results indicate that the majority of the dissolved CH 4 is advected and diffuses horizontally by turbulence whereas microbial oxidation, sea–air gas transfer, and vertical turbulent diffusion are less significant. Based on rates estimated in the study area, a model was developed to simulate the fate of the dissolved CH 4 . The model results suggest that 60% of the CH 4 of the sampled plumes will ultimately be microbially oxidized and 40% will be transferred to the atmosphere by sea–air gas exchange under the sampling conditions. These results illustrate the significance of microbial CH 4 oxidation in coastal oceans.

We report a new method for methane oxidation rate measurements that uses 103-105times less 14C-CH4 than existing measurements by taking advantage of the high sensitivity of accelerator mass spectrometry. Methane oxidation in the marine environment is a microbial process of global importance because it prevents methane released from underlying reservoirs from reaching the ocean and atmosphere. Rate measurements provide a crucial tool for assessing the efficacy of this process across a range of environments, but the current methods use high amounts of radioactive elements (3H- or 14C-CH4), tend to increase methane concentrations in a sample markedly over in situ levels, and are limited by strict health and safety regulations. The low-level method presented here uses levels of 14C-CH4 that are below transportation regulations, produce samples that do not require treatment as radioactive waste, and allow for tracer level rate measurements in low methane environments. Moreover, the low-level method lays the analytical foundation for a below-regulation rate measurement that could be used broadly and in-situ. Parallel rate measurements with the low-level 14C-CH4 and existing 3H-CH4 methods are generally consistent with a correlation coefficient of 0.77. However, the low-level method in most cases yields slower rates than the 3H method possibly due to temperature, priming, and detection limit effects.

Today's robotic systems are mostly rigid and position-controlled machines designed to operate in structured environments. To extend their application domains to partially unknown, dynamic, or anthropic environments, improved physical-interaction capabilities are required. In this new context, to blend the requirements for safety, robustness, and versatility is often a challenge, in part, because commonly available actuator technologies are inadequate. This paper presents our solution with the introduction of the dual-differential rheological actuator (DDRA) concept, which is based on the synergistic combination of an electromagnetic (EM) motor and two differentially coupled magnetorheological (MR) brakes. This paper describes the approach and the prototype design. It then discusses performances in force, motion, and interaction control.

Large quantities of methane (C1), ethane (C2), and propane (C3) emanate from shallow marine seeps near Coal Oil Point (COP), California. Concentrations of these gases were analyzed in the surface water down-current of the seep field over a 15-month period. The variable proportions of C1, C2, and C3 analyzed in gas bubbles emitted from 16 distinct seeps in the COP field encompass much of the variability found in the surface waters down-current. However, waters with disproportionate levels of C1 suggest the presence of additional C1 sources. Based on three spatial surveys, covering areas up to 280 km2, C2 and C3 air-sea fluxes were estimated to be in the order of 3.7 and 1.4 μmol day−1 m−2, respectively. Only 0.6% of C2 and 0.5% of C3 in the dissolved plume originating from the COP seep field are transferred to the atmosphere in the study area, with the fate of the remainder uncertain.

Introduction Mechanisms and participating substances involved in the reduction of glomerular filtration (GFR) in contrast-induced acute kidney injury (CI-AKI) are still matter of debate. We hypothesized that diadenosine polyphosphates are released by the action of contrast media on tubular cells and may act on glomerular arterioles and reduce GFR. Methods Freshly isolated rat tubules were treated with the contrast medium iodixanol (47 mg iodine per mL) at 37 °C for 20 min. The content of ApnA (n = 3–6) in the supernatant of treated tubules and in the plasma of healthy persons and patients with AKI was analysed using reversed-phase chromatography, affinity chromatography and mass spectrometry. GFR was obtained in conscious mice by inulin clearance. Concentration response curves for ApnA (n = 3–6, 10−12–10−5 mol L−1) were measured in isolated perfused glomerular arterioles. Results Iodixanol treatment of tubules significantly increased the concentration of ApnA (n = 3–5) in the supernatant. Ap6A was below the detection limit. AKI patient shows higher concentrations of ApnA compared to healthy. Application of Ap5A significantly reduced the GFR in conscious mice. Ap5A reduced afferent arteriolar diameters, but did not influence efferent arterioles. The constrictor effect on afferent arterioles was strong immediately after application, but weakened with time. Then, non-selective P2 inhibitor suramin blocked the Ap5A-induced constriction. Conclusion The data suggest that Ap5A plays a role in the pathophysiology of CI-AKI. We show a contrast media-induced release of Ap5A from tubules, which might increase afferent arteriolar resistance and reduce the GFR.

The aim of the present study was to investigate the pharmacokinetics of tilidine and its metabolites during the dialysis procedure and in the dialysis-free interval. Tilidine is a prodrug that is metabolized presystemically into the active metabolite nortilidine. Nortilidine is degraded thereafter to bisnortilidine and several polar metabolites. Nine patients with a creatinine clearance < 5 ml/min were treated in a crossover design with single oral doses of 1.5 mg/kg on the day of dialysis (dialysis performed from 3 to 6 hours after drug administration) and on a day in the dialysis-free interval. Blood samples were taken frequently and analyzed for tilidine, nortilidine, and bisnortilidine. Drug and metabolite concentrations were also measured in aliquots of dialysate collected during dialysis. Only negligible amounts of tilidine, nortilidine, and bisnortilidine (about 0.9% of the dose) were recovered from the dialysate. The pharmacokinetics of nortilidine and its inactive metabolite bisnortilidine was not affected by dialysis. The presystemic apparent clearance of the prodrug tilidine was decreased significantly during the dialysis-free interval. A significant decrease of the rate of elimination and an increase of the AUC of bisnortilidine were observed if these parameters were compared with data obtained from healthy volunteers. The plasma concentrations of nortilidine were comparable in patients and normal volunteers. Thus, a reduction of the dose of tilidine in patients with severely impaired kidney function seems not to be required. Tilidine and its metabolites cannot be removed from the body by dialysis.

• Background: The aim of the study was to compare the inward permeability of the blood-retinal barrier in healthy subjects from six European cities. • Methods: Seventy-two healthy subjects (age 20–70 years) were selected. At 30 min and 60 min after fluorescein injection, fluorescein mass in vitreous was calculated from the concentrations measured along the optical axis of the eye. Non-protein-bound fluorescein (NPBF) concentrations were measured in plasma prepared from blood samples taken 7, 15 and 55 min after injection. Blood-retinal barrier permeability (PBRB) was calculated from the vitreous fluorescein mass and the time integral of NPBF and was corrected for the autofluorescence of ocular tissue and for lenticular light transmittance. • Results: Mean PBRB values±SD (nm-−1) were 2.07±0.54 (Coimbra), 2.01±0.43 (Frankfurt), 2.24±0.50 (Ghent), 2.37±0.56 (Herlev), 1.89±0.44 (Leiden) and 1.74±0.38 (Porto). Differences between centers were not significant (P>0.35). Measurements were reproducible and independent of the time after fluorescein injection (P>0.50). A PBRB higher than 3.16 nm·s−1 or a value which had increased by 32% was considered abnormal (P

AIMS/BACKGROUND: Comparison of the diffusion coefficient through the blood-aqueous barrier of healthy volunteers measured in different cities with identical fluorophotometers using a standardised protocol. METHODS: Healthy volunteers aged between 20 and 70 years were studied in seven European cities. The fluorescein concentration in the anterior segment of each eye was measured with a commercial scanning fluorophotometer 30 and 40 minutes after intravenous fluorescein. The decay of non-protein bound fluorescein concentration in blood plasma was determined with the use of three blood samples taken at 7, 15, and 55 minutes after injection. The diffusion coefficient through the blood-aqueous barrier was calculated from the ratio between the fluorescein concentration in the anterior chamber and the time integral of non-protein bound fluorescein concentration in plasma using specially developed software. RESULTS: The mean values of the diffusion coefficient (SD) (X10(-4) min-1) were 4.76 (1.51) (n = 20, Brussels), 5.48 (2.33) (n = 17, Coimbra), 3.47 (2.09) (n = 12, Cologne), 6.09 (2.77) (n = 21, Frankfurt), 3.85 (1.59) (n = 11, Ghent), 4.99 (1.69) (n = 23, Leiden), and 4.87 (1.05) (n = 20, Madrid). The values between centres were similar (Kruskal-Wallis test p > 0.05) except for Cologne and Frankfurt (p = 0.013). No differences were found when repeating measurements (four centres, interval time 1-8 months, Wilcoxon paired test p > 0.39). CONCLUSION: The diffusion coefficients had similar values and standard deviations. The concerted action demonstrated the usefulness of a standardised protocol.

Diving into Deep Water The Deepwater Horizon oil spill in the Gulf of Mexico was one of the largest oil spills on record. Its setting at the bottom of the sea floor posed an unanticipated risk as substantial amounts of hydrocarbons leaked into the deepwater column. Three separate cruises identified and sampled deep underwater hydrocarbon plumes that existed in May and June, 2010—before the well head was ultimately sealed. Camilli et al. (p. 201 ; published online 19 August) used an automated underwater vehicle to assess the dimensions of a stabilized, diffuse underwater plume of oil that was 22 miles long and estimated the daily quantity of oil released from the well, based on the concentration and dimensions of the plume. Hazen et al. (p. 204 ; published online 26 August) also observed an underwater plume at the same depth and found that hydrocarbon-degrading bacteria were enriched in the plume and were breaking down some parts of the oil. Finally, Valentine et al. (p. 208 ; published online 16 September) found that natural gas, including propane and ethane, were also present in hydrocarbon plumes. These gases were broken down quickly by bacteria, but primed the system for biodegradation of larger hydrocarbons, including those comprising the leaking crude oil. Differences were observed in dissolved oxygen levels in the plumes (a proxy for bacterial respiration), which may reflect differences in the location of sampling or the aging of the plumes.

By means of a questionnaire and three personality tests, we investigated, whether there were any differences in the personality structure between patients who underwent an amniocentesis because of psychological indications, and a matched pair group of pregnant woman without amniocentesis. The results of the personality inventories showed no significant differences in the personality structure between both groups of pregnant women. In particular, they showed no difference with respect to the anxiety factor. As a result of our questionnaire we can state, that factors like education, the handicapped child in the environment, profession and the lack of commitment to bring up a handicapped child, influence the decision to undergo an amniocentesis.

Robots fail to perform complex manipulation or locomotion tasks when using simple force or motion controllers applied to classic actuators. Stability and safety issues arise for reasons such as high output inertia and the non-collocation of sensing and actuating transducers. This paper presents a new actuation concept, integrating a DC motor and two differentially coupled magnetorheological brakes, promising safe and versatile interaction capabilities. This paper focuses on the underlying mechanism and a case study with a proof-of-concept prototype.

Purpose: Computerized radiation therapy treatment planning is performed on almost all patients today. However it is seldom used for laboratory irradiations. The first objective is to assess whether modern radiation therapy treatment planning (RTP) systems accurately predict the subject dose by comparing in vivo and decedent dose measurements to calculated doses. The other objective is determine the importance of using a RTP system for laboratory irradiations. Methods: 5 MOSFET radiation dosimeters were placed enterically in each subject (2 sedated Rhesus Macaques) to measure the absorbed dose at 5 levels (carina, lung, heart, liver and rectum) during whole body irradiation. The subjects were treated with large opposed lateral fields and extended distances to cover the entire subject using a Varian 600C linac. CT simulation was performed ante-mortem (AM) and post-mortem (PM). To compare AM and PM doses, calculation points were placed at the location of each dosimeter in the treatment plan. The measured results were compared to the results using Varian Eclipse and Prowess Panther RTP systems. Results: The Varian and Prowess treatment planning system agreed to within in +1.5% for both subjects. However there were significant differences between the measured and calculated doses. For both animals the calculated central axis dose was higher than prescribed by 3–5%. This was caused in part by inaccurate measurement of animal thickness at the time of irradiation. For one subject the doses ranged from 4% to 7% high and the other subject the doses ranged 7% to 14% high when compared to the RTP doses. Conclusions: Our results suggest that using proper CT RTP system can more accurately deliver the prescribed dose to laboratory subjects. It also shows that there is significant dose variation in such subjects when inhomogeneities are not considered in the planning process.

Atherosclerotic renal artery stenosis accounts for most cases of renovascular hypertension (RVH). Hypertensive patients with clinical features suggesting RVH should be submitted to further noninvasive evaluation including duplex Doppler ultrasonography, CT- or MR angiography. Invasive evaluation by contrast-enhanced angiography confirms the diagnosis of renal artery stenosis. However, neither diagnostic test reliably predicts the course of hypertension after revascularisation. The therapeutic approach in hypertensive patients with hemodynamically important renal artery stenosis includes medical or invasive therapy (renal percutaneous transluminal angioplasty, PTRA; renal arterial stent placement, PTRAS; surgical revascularisation). Randomized trials comparing invasive and conservative approaches demonstrated no differences in blood pressure control or renal function. Only patients with clear clinical indications should be submitted to interventional procedures as PTRA, PTRAS and surgical vascular intervention.

The number of patients with end-stage renal disease is constantly growing. If patients at risk are identified early enough, currently available therapeutic options allow a potent primary and secondary prevention of progressive renal failure. If the underlying disease can not be eliminated, the mainstay of the therapy are supportive measures such as antihypertensive and, in case of an underlying diabetes mellitus, antidiabetic therapy, dietary restrictions as well as avoidance of additional nephrotoxic agents. Furthermore, even a mild renal insufficiency has been identified as a potent cardiovascular risk factor. The second major goal of supportive therapy therefore is a reduction of the markedly increased cardiovascular morbidity of these patients. This can be achieved through treatment of various consequences of renal failure, such as hyperparathyroidism, renal anemia etc. Supportive therapy thus represents a highly complex and interdisciplinary treatment, which should prompt an early inclusion of a nephrologist into the therapeutic strategy.

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 +/- 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40 U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (deltaBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (RD Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 +/- 0.36 pg/ml) when compared to healthy controls (ref. 0.3-0.9) and increased to 1.47 +/- 0.51 pg/ml by the end of the session (p0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 +/- 0.3 vs. 1.05 +/- 0.3 pg/ml) and at the end of HD (1.62 +/- 0.5 vs. 1.28 +/- 0.3 pg/ml, p0.05). There was no difference in BP and deltaBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.

Patients with chronic renal failure under maintenance hemodialysis (HD) present with numerous adverse effects including immunologic alterations. Serious abnormalities of neutrophil function have been reported to be associated with disturbed cell adhesiveness. These adhesion processes are mediated by cytokines and different adhesion molecules.In this study, serum concentrations of the intercellular adhesion molecule ICAM-1, vascular cell adhesion molecule VCAM-1 and endothelial leukocyte adhesion molecule E-selectin were investigated during employment of different dialysis membranes (cuprophane: n = 23, cellulose: 8, polysulfone: 26, acrylonitrile: 7). These adhesion parameters from 64 patients before and after a hemodialysis session were investigated parallel to the serum levels of circulating cytokines and their inhibitors.Circulating ICAM-1 levels were not elevated in low-flux membranes and most of the high-flux HD membranes, except for one high-flux polysulfone membrane. cVCAM-1 levels were significantly elevated both in low- and high-flux dialysis membranes, whereas cE-selectin was not increased. cICAM-1 levels were not different before and after hemodialysis in the entire study group. In contrast, cVCAM-1 and cE-selectin levels increased significantly during HD in the entire study group (both p0.001). Serum levels did not correlate with the duration of end-stage renal failure and hemodialysis. Levels of circulating cytokine antagonists/inhibitors (Il-lra, Il-2R, TNFsRp55/75) were significantly increased in all patients before and after HD, whereas the serum concentrations of the corresponding circulating cytokines (I1-1beta, Il-1, TNF-alpha) were within normal ranges.Increased levels of cVCAM-1 which suggest an important role for immunological alterations in HD and cytokine-independent changes during HD sessions in all membranes without alterations of cICAM-1 in most membranes and unchanged cE-selectin indicate that processes such as uremia are responsible for these effects rather than membrane characteristics. The level of circulating adhesion molecules does not serve as an appropriate marker of membrane biocompatibility.

Purpose: Comparison of 2D electronic array systems with film for IMRT QA. Method and Materials: Two electronic array systems, MapCHECK (SunNuclear) and MatriXX (Scanditronix), were evaluated and compared with EDR2, XV, and Gafchromic EBT film. Patient evaluations included two HN a standard method (such as 2D array) and a more detailed backup method (such as film). 2D arrays can provide a complete QA package with resolution limitations. Film analysis for MapCHECK is awkward at best with GafChromic analysis for both MapCHECK and MatriXX being better but demonstrated difficulties in user friendliness and final values. The MatriXX film analysis was preferred.

Purpose: Evaluation and comparison of 2D electronic systems versus film/ion chamber based dosimetry for IMRT QA using MapCHECK and MatriXX. Method and Materials: All IMRT plans were generated with Eclipse/Helios 7.3.10 treatment planning software (Varian). Treatments were delivered on a Varian 21EX linear accelerator (6MV) with 120 leaf Millenium MLC for delivery of sliding window IMRT. The film measurements were first compared to the Eclipse dose plane. Secondly, the electronic measurements were compared to the Eclipse dose plane. Thirdly, the film measurements were compared to the electronic measurements. The film, Eclipse dose plane and MatriXX (Scanditronix) were analyzed using the OmniPro IMRT software (Scanditronix). The film, Eclipse dose plane and MapCHECK (SunNuclear) were analyzed using the MapCHECK software. Analysis was based on distance to agreement (DTA), Gamma, profile comparisons, measured dose (relative/absolute) and visual comparison. Results: Film and ion chamber comparisons were in good agreement as well as comparisons between electronic and ion chamber measurements. However, in some instances, electronic system measurements did not agree with film due to MLC leaf failure. Advantages and disadvantages of MatriXX and MapCheck for IMRT QA as well as specific MLC leaf failure instances will be discussed further. Conclusion: With many clinics implementing electronic IMRT QA devices, a careful understanding of the limitations of the MLC system and the electronic IMRT QA device is needed. We are investigating the resolution capabilities of each QA system. The MLC failure was caught before treatment began. A major disadvantage in implementing 2D electronic systems for IMRT QA is the limited resolution, resulting in limited sensitivity to MLC failures. Primary advantages of 2D electronic systems include: 1) time, 2) efficiency, 3) ease of use, and 4) overall simplification of IMRT QA.

The relative bioavailability of a new formulation of verapamil (CAS 52-53-9, Veramex 40) in comparison to a standard formulation was investigated in an open two-period cross-over study in 16 healthy volunteers under steady state conditions of 7 days duration each. For the estimation of verapamil a selective HPLC-method was used with fluorescence detection after direct injection and enrichment by column switching enabling a simultaneous separation and analysis of verapamil and N-norverapamil. The bioavailability was estimated using areas under the concentration-time curves (AUC), maximum serum concentrations (Cmax) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVAlog). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference substance, thereafter slightly higher plasma levels up to 7 h were observed after the test substance. The individual plasma profiles had a similar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean relative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concentrations for verapamil and N-norverapamil were 50.0 and 49.7 ng/ml, respectively. After the standard formulation the corresponding values were 50.4 and 50.3 ng/ml. The mean PTF-values for verapamil and N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, respectively. The 90% confidence intervals for AUC, Cmax and PTF for verapamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, Cmax and PTF. Therefore bioequivalence between both formulations can be stated.

The arterial wall structure degenerates with increasing age, elastin fibers decrease while collagen increases. We investigated the elastic properties of the aorta and iliac arteries to determine the relationship between aging and arterial mechanics. The regional elasticity of the aorta and iliac arteries was determined at five different sites in 40 normotensive patients aged 32 to 78 years. A combined procedure for arterial blood pressure measurement and arterial cross-sectional area determination was employed to calculate the parameters of compliance and pulse wave velocity. The descending thoracic and abdominal aorta showed significant correlations between age and elasticity. No correlation was observed at the aortic bifurcation. A significant correlation between age and pulse wave velocity was apparent in the common iliac artery, whereas compliance showed no significant correlation to age. In the external iliac artery as well, no significant correlation between age and elasticity could be found. Arterial elasticity decreases with age, but this process does not progress uniformly at all sites of the arterial system. The difference in elasticity between these basic types of arteries diminishes throughout life. At the aortic bifurcation, mechanical aging seems to proceed faster than at unbifurcated arterial segments.

Patients with diabetes mellitus commonly exhibit pathological lipoprotein profiles and concomitant cardiovascular or peripheral atherosclerotic complications. Thirty non-insulin-dependent diabetics with secondary hyperlipidemia received 2.7 g 3-sn-polyenylphosphatidylcholine (PPC) or placebo daily, orally over a 2-month period under randomized, double-blind trial conditions, to investigate the efficacy and tolerance of the treatment. This period was followed by a one-month observation phase without investigational medication. Serum LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides were determined on days 1, 14, 28, 56 and 84. After 56 days of treatment with PPC, the primary variable of effectiveness, LDL cholesterol, decreased significantly (p = 0.0174) by 17% from 191 +/- 31 to 159 +/- 36 mg/dl, whereas values did not change in the placebo group. Total cholesterol (TC) in serum decreased by 16% from 303 +/- 22 to 255 +/- 23 mg/dl with PPC. In the placebo group, only a slight decrease from 292 +/- 27 to 289 +/- 41 mg/dl occurred. Mean serum triglyceride (TG) levels fell by 9% from 194 +/- 32 to 177 +/- 27 mg/dl in the PPC group. In the control group, values increased from 193 +/- 34 to 202 +/- 41 mg/dl. The differences in LDL, TC and TG between the treatment groups were statistically significant; p = 0.0014, p = 0.0001 and p = 0.007, respectively. HDL cholesterol in serum increased 12% from 50 +/- 10 to 55 +/- 13 mg/dl after PPC application. The control group did not show any alteration of mean HDL cholesterol level at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Local elastic properties of the descending aorta at different levels were evaluated by means of intravascular ultrasound images and pressure measurements. For this purpose, 30 normotensive patients and 30 age-matched medically treated patients with essential hypertension, all undergoing diagnostic cardiac catheterization, were studied.Hypertension was well controlled in the essential hypertensives (137.1 +/- 6.79/74.5 +/- 2.65 mmHg). Systolic but not diastolic blood pressure in the hypertensive patients was significantly different from that of the normotensives (118.8 +/- 4.38/69.7 +/- 1.65 mmHg). The continuous loss of volume compliance with increasing distance from the heart was significantly higher in the hypertensives than in the normotensive patients [normotensives (1.45 +/- 0.19) x 10(-10) m5/N at the thoracic aorta, (0.08 +/- 0.05) x 10(-10) m5/N at the external iliac artery; hypertensives (0.81 +/- 0.09) x 10(-10) and (0.05 +/- 0.01) x 10(-10) m5/N at the corresponding sites]. Similarly, the hypertensives had an elevated elastic modulus proximal to the aortic bifurcation compared with the normotensives (244.47 +/- 44.06 versus 108.10 +/- 17.76 m/s, respectively). The decrease in buffering function of the vessel at this site is presumably caused by a turbulent flow pattern. Compared with the normotensives, the treated hypertensives had a significantly higher elastic modulus at each site where this was measured, whereas volume compliance and sectional compliance were lower.The differences in elastic modulus and compliance between hypertensive and normotensive patients seem disproportionate to the difference in systolic blood pressure (within the normal range in both the treated hypertensives and the normotensives). Therefore, normalization of high blood pressure by long-term antihypertensive treatment may not fully reverse changes, caused by arterial hypertension, in the viscoelastic properties of the arterial wall.

Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple doses (14 days) of ramipril (5 mg once daily); the concentrations of ramipril and ramiprilat in plasma, as well as ramipril, ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine were measured at various times for 14 days. One patient dropped out after the first day due to hypotension and another who accidentally received another ACE inhibitor additionally was excluded, so that 11 patients completed the study. Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and ramipril and its metabolites in urine were measured by gas chromatography in the laboratories of Hoechst AG. Peak concentrations of the active substance ramiprilat were reached after about 4 h and amounted to 22.3 +/- 11.1 ng/ml after the first dose, and a peak concentration of 26.6 +/- 10.0 ng/ml was observed 2.5 +/- 1.4 h on average after administration on day 14. Practically no accumulation was observed for ramiprilat; the AUD (0-24 h) values increased from 191.3 +/- 83.1 ng.h/ml for the first study day to 238.3 +/- 98.0 ng.h/ml for day 14. As expected, only very small fractions of the dose were excreted with urine as unchanged ramipril and ramipril glucuronide. Ramiprilat is excreted with urine to a larger extent than is rampiril--on average 6.6 +/- 3.0% on the first day and 12.2 +/- 3.8% on day 14. The total amount excreted increased by 34% on average, and was mainly due to an increased ramiprilat excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Guar smoothens postprandial glucose peaks and reduces serum cholesterol. Both properties are advantageous for diabetic patients and can be realized, in part, by adding fiber to the diet. Depending on the blood glucose concentration, a small portion is incorporated into hemoglobin (HbA1), building a largely irreversible complex, making it a long-term indicator of blood glucose status. HbA1 may increase from a normal value of about 5% to as much as 20% of total hemoglobin in diabetics. This study tested the efficacy of two guar preparations in diabetic patients over 3 months by measuring HbA1, cholesterol and triglycerides. Forty diabetic patients with HbA110% ingested either 3 x 4 g daily of a new guar preparation (GU-052, Steigerwald, Darmstadt, Germany) or 3 x 5 g daily of Glucotard (Boehringer, Mannheim, Germany) for 12 weeks. Before and after 30, 60 and 90 days of treatment, HbA1, cholesterol and triglycerides were determined. After 90 days of treatment, GU-052 caused a reduction in HbA1 from 12.6 +/- 2.6% to 10.5 +/- 1.5% (-15.6 +/- 9.0%) in the GU-052 group and from 12.0 +/- 2.6% to 10.9 +/- 1.82% (-8.6 +/- 7.2%) in the Glucotard group. Cholesterol was reduced from 269 +/- 28 mg/100 ml on day 0 to 227 +/- 18 mg/100 ml on day 90 in the GU-052 group and from 261 +/- 40 to 235 +/- 26 mg/100 ml in the Glucotard group. Both GU-052 and Glucotard had little effect on plasma triglycerides. Fewer unpleasant side effects were reported for the GU-052 preparation than for Glucotard.(ABSTRACT TRUNCATED AT 250 WORDS)

A 13-year-old boy presented with juvenile X-linked retinoschisis and in the right fundus a typical retinal angioma situated at the temporal site of the macula. A maternal uncle and a maternal grand uncle were known to be also affected by juvenile retinoschisis. Family history was negative for retinal angiomatosis. Extensive internal, neurologic and radiologic examinations did not reveal associated neurologic or visceral involvement in the affected child. The association of a retinal angioma and juvenile X-linked retinoschisis is most probably fortuitous.

By means of a questionnaire and three personality tests, we investigated, whether there were any differences in the personality structure between patients who underwent an amniocentesis because of psychological indications, and a matched pair group of pregnant woman without amniocentesis. The results of the personality inventories showed no significant differences in the personality structure between both groups of pregnant women. In particular, they showed no difference with respect to the anxiety factor. As a result of our questionnaire we can state, that factors like education, the handicapped child in the environment, profession and the lack of commitment to bring up a handicapped child, influence the decision to undergo an amniocentesis.

The effects of reduced blood volume during hemodialysis on circulating immunoreactive parathyroid hormone (PTH) were determined in relation to changes in blood pressure and heart rate in normo- and hypotensive patients with end stage renal failure. During dialysis the plasma concentration of PTH did not change in normotensives, while PTH increased significantly in patients with a fall in blood pressure during a 25% reduction in effective intravascular volume. The blood volume was measured continuously during hemodialysis using the authors' hemoglobin measurement system. The decrease in blood volume in both groups was comparable. The results suggest that secretion of PTH during hemodialysis may play a role in hemodynamic instability during hemodialysis.

In an open trial 5 mg ramipril daily for 2 weeks was administered to 11 patients with congestive heart failure. 24-hour plasma profiles of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), angiotensin II (Ang II) and aldosterone (Aldo) were determined before and on days 1 and 15 of ramipril treatment, respectively. Urinary sodium excretion was also measured at the same time points. There were no relevant differences in the 24-hour profiles of ANP and ADH. Ang II values dropped as expected on the first day of ramipril treatment from 11.2 pg/ml to 2.9 pg/ml at 3 h post administration and from 6.7 pg/ml (predose) to 1.8 pg/ml at 2 h post administration on day 15. Plasma aldosterone values increased slightly from day 1 to day 15, sodium excretion increased from 125.9 mmol to 166.5 mmol/24 h; however, both changes in the 24-hour profiles were nonsignificant. A clinically relevant improvement in the severity of CHF was observed. From a total of 121 reported symptoms according to McKee et al., 35 showed an improvement; 81 remained unchanged, in only 5 symptoms a deterioration was observed. According to the NYHA-classification 5 patients improved from grade III to II, 6 remained unchanged.ACE inhibition does not induce changes in ANP or ADH levels in the resting state while Ang II decreases. A slight increase in aldosterone levels may be due to increased sodium excretion.

Prostaglandin synthesis in renal tissue is required for loop diuretic induced extrarenal vascular effects in animals. Indomethacin, a prostaglandin synthesis inhibitor, diminishes the diuretic effect of furosemide. Three studies in patients with congestive heart failure, renal failure or aortic insufficiency have shown that hemodynamics and renal effects of acute and chronically applied piretanide correlate with an increase in vasodilatory prostaglandins.

Ramipril was administered to 13 patients, aged 49-80 years, weighing 53.5-90.3 kg, with congestive heart failure (CHF) for 2 weeks in an open trial. One patient dropped out after day 1 and another accidentally received another angiotensin-converting enzyme (ACE) inhibitor, so that 11 patients remained for analysis. Each patient received 5 mg of ramipril daily for 2 weeks, followed by a 1-week washout period. Urine was collected in 4-h fractions for 12 h followed by a 12-h fraction on days 1, 8, and 15. Creatinine clearance, as well as the excretion of albumin and the urinary brush border enzymes gamma-glutamyl transferase (GGT), alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG), and lactate dehydrogenase (LDH) were determined. The values for albumin excretion, creatinine clearance, GGT, AAP, NAG, and LDH obtained for the various days during the time course before and during multiple dosing were subjected to an analysis of variance followed by Scheffe's test for means. Daily albumin excretion decreased during treatment with ramipril from 23.8 +/- 27.4 mg/24 h (baseline) to 12.9 +/- 15.1 (day 1), 10.8 +/- 15.6 (day 8), and 12.4 +/- 12.7 mg/24 h (day 15). The differences were significant (alpha = 0.05) when compared to pretreatment albumin excretion. Creatinine clearance increased from 78.8 +/- 38.3 ml/min (baseline) to 82.4 +/- 34.6 (day 1), 85.1 +/- 28.5 (day 8), and 91.7 +/- 36.4 ml/min (day 15). The change on day 15 was significant (alpha = 0.05) when compared to pretreatment values.(ABSTRACT TRUNCATED AT 250 WORDS)

This randomised, parallel group study was designed to compare the efficacy of nifedipine (40 mg once daily) combined with either the dopamine agonist, co-dergocrine mesilate (4 mg once daily) or the diuretic mefruside (25 mg once daily) in 40 patients with essential arterial hypertension and a diastolic blood pressure greater than 105 mmHg. Circadian blood pressure and heart rate were measured over 24 h every 15 min from 6 a.m. to 6 p.m. and every 30 min from 6 p.m. to 6 a.m. with an automatic, portable instrument (ICR 5300, Squibb) before and after a three-week treatment period. At the end of the three-week treatment period the mean value of all 24 h blood pressure measurements reflected highly significant decreases (2P less than 0.001), from 148/92 +/- 16/12 before treatment to 131/83 +/- 12/12 mmHg after treatment in the co-dergocrine mesilate/nifedipine group and from 145/92 +/- 16/10 before treatment to 129/84 +/- 10/6 mmHg after treatment in the mefruside/nifedipine group. Blood pressure reduction was still significant in both groups during the early morning hours at the end of the dosage interval. The efficacies of nifedipine combined with co-dergocrine mesilate or mefruside were comparable but side-effects were rated as more severe in the mefruside group. Therefore, the combination co-dergocrine mesilate/nifedipine may be preferable to the combination mefruside/nifedipine.

A 23-year-old man survived a suicide attempt in which he had swallowed 1500 mg potassium cyanide. Initially there were cerebral seizure and marked lactacidosis. Six hours after hospital admission the cyanide blood level was 6 mg/l. The poisoning having at first not been recognized he at that time merely received supportive treatment to counteract the acidosis, as well as assisted ventilation with hyperventilation and hyperoxigenation. Afterwards, sodium thiosulphate was given additionally for 24 h at a dosage of 1 g per hour. The clinical course underlines the great importance of supportive measures in the treatment of cyanide poisoning. In the individual case the balance between risk and value of an intrinsically toxic antidote administration must be critically assessed.