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Reduced pulmonary diffusion capacity is a hallmark of COPD, although the relative contribution of the subcomponents of pulmonary diffusion--membranous component (Dm) and capillary volume (Vc)--is unknown. These components can be measured with the method of NO single-breath diffusion (DLNO). In a prospective study, pulmonary function tests including spirometry, body plethysmography and single-breath measurements of diffusion capacity with CO and NO were performed in 183 patients with COPD of varying severity. There was a severity-dependent decrease in DLCO. Furthermore, Dm as well as Vc was positively correlated with the severity of COPD measured by FEV1. In all stages of COPD, reduction of Vc was more pronounced than constriction of Dm. In patients with most severe COPD, the preponderance of the reduction of Vc was significantly more marked than in milder stages.We conclude that Dm as well as Vc contributes to the reduction of DLCO in COPD, with a predominance of Vc at all stages of COPD. This confirms the idea that the loss of pulmonary capillaries in COPD is functionally relevant.

METHODS The pancreas of 24 male Wistar rats was perfused extracoporally by modified Krebs-Ringer-buffer for 80 minutes (including a 20 minutes equilibration period). To verify any organ damage we measured the activity of pancreatic enzymes like amylase, lipase and lactatdehydrogenase in the portal effluent. Furthermore histological changes were analysed after perfusion. Organ damage was induced by adding cerulein in a physiological dose (10(-10) M, n = 6) and in a supramaximal dose (10(-8) M, n = 6) and by intraductal injection of taurocholate (3.5 %, n = 6). RESULTS Already 10 minutes after stimulation with cerulein (10(-8) M) and after intraductal injection of taurocholate increased activities (p < 0.01) of amylase and lipase were measured in the portal effluent compared to the group without any treatment. Lactatdehydrogenase levels did not changed. Apart from marked oedema in both groups considerable zones of necrosis could be noticed especially in the taurocholate group. CONCLUSION Our data suggest that the isolated perfused rat pancreas (IPRP) is a valuable experimental tool to verify pathophysiological changes in the early phase of acute pancreatitis (AP). Various established models of AP such as by cerulein hyperstimulation or intraductal injection of taurocholate, could be applied to the IPRP. We conclude that this method enlarges the spectrum of established experimental models of acute pancreatitis.

A study was performed exposing seven automotive OEM coatings (base coat/clear coat paint systems) outdoors in Jacksonville and to different variants of the acid dew and fog (ADF) test, a new approach to simulating the worst case of the weather conditions in harsh urban and industrial environments. Varying the climatic conditions and the severity of the simulated acid precipitation, a certain variant of the ADF test was found to show a satisfying practice correlation. Profilometric and chemical analysis revealed that the coatings differ in the rate of photodegradation after an acid attack due to the penetration of acid solution.

Antireflexstrukturen konnen durch zusatzliche Beschichtungen superhydrophobe oder auch langzeitstabile superhydrophile Eigenschaften erlangen. Die durch Plasmaatzen erzeugten Strukturen sind dabei deutlich kleiner als die Wellenlangen des sichtbaren Lichtes und erhohen auch die Transmission der modifizierten Proben. Noppenartige Strukturen mit grosem Aspektverhaltnis erreichen den Lotus-Zustand unmittelbar nach Uberschichten mit einem hydrophoben Material. Bei PMMA wird ein Lotus-Effekt erst dann beobachtet, wenn unter der hydrophoben Deckschicht noch eine dunne SiO2-Schicht angeordnet wird. Controlled wetting of optical polymers by antireflective structures and thin films The wetting behaviour of antireflective structures can be modified by additional coatings to become superhydrophobic or hydrophilic. The sub-wavelength structures which increase the samples transmission are generated by plasma etching. Bump structures with large aspect ratio show a Lotus-like behaviour immediately after coating with a thin hydrophobic layer. In case of PMMA the Lotus-state can only be achieved if a thin silica layer is arranged below the hydrophobic top-layer.

Postoperative irradiation was done in 12 female patients with granulosa cell tumours between 1962 and 1981. The average follow-up period was 10 years and 10 females were alive without evidence of renewed tumour growth. A further patient died of cardiac infarction after 7 years. At the time of death she was free of recurrence or metastases. Only in one case multiple filiae developed in the lung, liver and skeleton 8 months after cessation of irradiation. The progression of these could not be arrested. Following the first therapeutic step, i.e. abdominal hysterectomy and bilateral adnectomy , radiotherapy represents an important additional therapeutic measure. Thus the unfavourable long-term prognosis of granulosa cell tumours can be beneficially influenced particularly in far-advanced cases or in recurrences.

Oral drug treatment of detrusor overactivity often causes undesirable side effects in other organs. For some patients, in particular those with neurogenically induced detrusor overactivity (detrusor hyperreflexia), the tolerance level for adverse effects is low and oral treatment may become ineffective. Intravesical administration of the drug can diminish the side effects or increase treatment effectivity in patients who are (partially) refractory to oral treatment because the relative concentration of the drug is increased in the target organ and decreased in the circulation. Six men (19-34 years old) with traumatic spinal cord lesions between C2 and Th11 were randomized to intravesical instillation with 15 or 30 mg trospium chloride in 40 ml saline into the empty bladder. Catheterization was postponed until at least 3 h after instillation, and fluid intake was not allowed during the first 4 h. Blood samples were taken before and 11 times after instillation; the last sample 12 h post instillation. Four positive samples were found in three patients: 0.10 ng/ml after 1 h and 0.13 ng/ml after 2(1/2) h in two patients with 15 mg, and 0.24 ng/ml after 30 min and 0.70 ng/ml after 6 h in one patient with 30 mg instilled trospium chloride. Three adverse effects were reported and were rated as probably not related to the drug. It is concluded that intravesically instilled trospium chloride is not absorbed into the circulation in significant amounts and, thus, it may be expected that this mode of administration will improve the efficacy of trospium chloride therapy by reducing the side effects. Neurourol. Urodynam. 18:447-453, 1999.

Mg2+-ions have been suspected to attenuate the inhibitory effect of allosteric modulators on the dissociation of orthosteric ligands from muscarinic M2 receptors. It was aimed to gain more insight into the molecular events underlying the effect of Mg2+. The interaction of Mg2+ with the allosteric model compounds W84 (hexane-1,6-bis [dimethyl-3’-phthalimidopropylammonium bromide]) and Chin3/6 (hexane-1,6-bis[dimethyl-3’-{4-oxo-2-phenyl-3,4-dihydro-2H-quinazolin-1-yl}propylammonium bromide]) was studied in porcine heart muscarinic receptors, the primary binding site of which was occupied by the ligand [3H]N-methylscopolamine ([3H]NMS). The incubation buffer was composed of 4 mM Na2HPO4 and 1 mM KH2PO4 (pH 7.4, 23°C). The retardation of [3H]NMS dissociation (control t1/2 = 5.6 min) induced by the allosteric test compounds was diminished by 3 mM Mg2+ to a greater extent than to be expected with regard to its contribution to the ionic strength of the buffer solution. Concentration-effect curves for the allosteric retardation of [3H]NMS dissociation by W84 (half maximal effective concentration EC0.5 = 24 nM in the absence of Mg2+) and by Chin3/6 (EC0.5 = 28 nM) were shifted by Mg2+ to the right in a parallel fashion. The curve-shift was compatible with a competitive interplay between Mg2+ and the modulators. The pK b-values as a measure of the antagonistic potency of Mg2+, however, differed depending on the modulator, i.e. pK b = 3.4 with W84 and pK b = 2.8 with Chin3/6. Mg2+ itself was capable of slowing the dissociation of [3H]NMS; the maximal retardation of [3H]NMS dissociation was about 3fold, the concentration-effect relationship was compatible with a two-site model using the above-mentioned pK b-values as affinity constants. Since the equilibrium-binding of [3H]NMS remained unchanged up to a Mg2+-concentration of 3 mM, the cation appears to inhibit the association and dissociation of [3H]NMS to the same extent in this concentration range. Taken together, the findings indicate that Mg2+ may bind to the allosteric region of muscarinic M2 receptors and that more than one site is involved in this interaction. The sites of action may represent divalent cation binding sites.

When combining languages for symbolic constraints, one is typically faced with the problem of how to treat “mixed” constraints. The two main problems are (1) how to define a combined solution structure over which these constraints are to be solved, and (2) how to combine the constraint solving methods for pure constraints into one for mixed constraints. The paper introduces the notion of a “free amalgamated product” as a possible solution to the first problem. We define so-called quasi-free structures (called “strong simply-combinable structures” in a previous publication) as a generalization of free structures. For quasi-free structures over disjoint signatures, we describe a canonical amalgamation construction that yields the free amalgamated product. The combination techniques known from unification theory can be used to combine constraint solvers for quasi-free structures over disjoint signatures into a solver for their free amalgamated product. In addition to term algebras modulo equational theories (i.e., free algebras), the class of quasi-free structures contains many solution structures that are of interest in constraint logic programming, such as the algebra of rational trees, feature structures, and domains consisting of hereditarily finite (well-founded or non-well-founded) nested sets and lists.

Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy.

A theoretical model based on the model of elasticity is used to simulate the stress field of several simplified single- and multilayer coatings under indentation load. Based on these results the stresses relevant for the failure of the coating are identified. The influence of different coating parameters like thickness, material choice and layer arrangement is examined. The results of this analysis are considered when designing an antireflective coating with optimized mechanical resilience. A modified coating is deposited and the scratch resistance is compared to an established coating. As indicated by the simulation the optimized coating shows an enhanced scratch resistance.

The present study evaluates the effect of free radicals generated by xanthine oxidase-catalyzed oxidation of hypoxanthine on cellular function of isolated rat pancreatic acinar cells. The results show that a rapid and sustained increase in intracellular Ca 2+ concentration ([Ca 2 +] i ) preceded all other morphological and functional alterations investigated. Radical-induced [Ca 2+ ] i increase was largely inhibited by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, which prevents Ca 2+ release from intracellular stores, but not by Ca 2+ -depleted medium. Radicals released Ca 2+ from thapsigargin-insensitive, ryanodine-sensitive intracellular stores, whereas the secretagogue caerulein at physiological concentrations mainly released Ca 2+ from thapsigargin-sensitive stores. In contrast to effects of the secretagogue, radical-induced Ca 2+ changes did not cause luminal protein secretion but cell death. In single-cell measurements, both secretagogue and radicals induced oscillations of [Ca 2+ ] i . Radical-induced oscillations had a lower frequency but similar amplitude when compared with caerulein-induced oscillations. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and ryanodine, which prevented the radical-induced Ca 2+ increase without altering the generation of radicals, markedly reduced the radical-induced cell damage. These results suggest that the Ca 2+ increase mediates the radical-induced cell injury. The studies also indicate that not only the extent and duration but also the origin of [Ca 2+ ] i release as well as the frequency of Ca 2+ oscillations may determine whether a pancreatic acinar cell will secrete or die.

HISTORY AND INTERVENTION: A 52-year-old female patient underwent open abdominothoracic cardia and esophageal resection with gastric transposition because of histologically diagnosed Barrett metaplasia with "high-grade" intraepithelial neoplasia (HGIEN) and parts of an invasive adenocarcinoma. The anastomotic insufficiency on the 10th postoperative day including an esophagobronchial fistula prompted to a subsequent surgical re-intervention with suture of the fistula, lavage and additional drainage, an endoscopic stenting of the fistula from esophageal site, as well as repeated (n = 22) bronchoscopic applications of fibrin glue (1-3 ml each) into the lumen of the fistula after each bronchoscopic lavage of the fistula until the complete closure was achieved. The changeful clinical course of 77 days on the surgical ICU was characterized by secondary complications such as pneumonia, mediastinitis and respiratory insufficiency with long-term artificial respiration and creation of a percutaneous dilatation tracheotomy.The application of fibrin glue can be considered a promising, minimally invasive therapeutic option in the management of postoperative fistula after esophageal resection, which requires expertise in decision-making and the finding-specific approach, in particular, if indicated inital steps of the sequential complication management such as surgical re-intervention and conventional endoscopic measures (stenting, Endo-VAC[-sponge]) do not provide great therapeutic potential any more due to the prolonged postoperative time course and the unfavorable local findings. In the presented case, modes of an assisted artificial respiration with low pressure and short phases of apnoe after fibrin glue application were the crucial predictions for an initial and favorable adhesion of this glue and finally for a successful sealing resulting in a sufficient closure of the fistula.

Summary Objective It was the aim of this prospective randomized multicenter study to compare chemotherapy and radiotherapy as consolidation treatments in patients achieving complete remission (CR) after 6 cycles of doxorubicin-containing chemotherapy in advanced-stage Hodgkin's disease (HD). Methods A total of 288 previously untreated patients aged 18–60 years with stage IIIB or IV HD received induction chemotherapy with 3 × (COPP + ABVD). Patients achieving CR were eligible for randomisation to either 20 Gy radiotherapy to initially involved fields (RT-arm) or to an additional 1 × (COPP + ABVD) (CT-arm). Patients with nodal PR were allocated to more intense radiotherapy (IRTarm: 20 Gy IF, 40 Gy to persisting tumor). Four patients with persisting organ involvement after induction received salvage chemotherapy. Results Of 288 patients, 171 (59%) achieved CR after induction chemotherapy. Of these, 100 patients were successfully randomized to RT or CT. In the CT arm relapses were observed in 10 of 49 patients compared with 13 of 51 patients in the RT arm (p = n.s.). Fifty patients refused randomisation and for them a treatment was chosen, and 21 patients refused any further treatment. Of these 21 patients with no consolidation therapy, 9 relapsed, indicating an approximately 3-fold increased relapse risk compared with those receiving either of the consolidation therapies. No relapse was observed in initially involved lung or liver sites. Adverse prognostic factors for freedom from treatment failure and survival were low hemoglobin and large mediastinal mass at initial presentation. Conclusions No statistically significant differences in treatment efficacy were detected between 20 Gy IF radiotherapy and 1 × (COPP + ABVD) chemotherapy following CR after six cycles of alternating chemotherapy in patients with advanced-stage HD. However, limited observations in a non-randomized cohort indicate that patients without consolidation treatment of CR after 6 cycles of chemotherapy may have an elevated risk for relapse.

470 Extracardiac endothelium patterns embryonic coronary arterio-venous connections {#article-title-2} Recent reports suggest that mammalian embryonic coronary endothelium (CoE) develops from the sinus venosus and ventricular endocardium. Although several studies in non-mammalian vertebrates have proven that extracardiac endothelial cells also participate in CoE development, the contribution of such cells to mammalian CoE is regarded to be minor and non-significant. Using classic (Wt1Cre) and novel (G2-Gata4Cre) mouse transgenic models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardiun (ST/PE)-derived endothelial cells are required for proper coronary development. Our results indicate that, at least, 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE. Conditional deletion of the epicardial lineage gene Wt1 in the ST/PE (G2-Gata4Cre) or the endothelium (Tie2Cre) reveals a critical role for these ST/PE-derived endothelial cells in the establishment of transmural ventricular coronary arterio-venous connections. Taken together, our results confirm that embryonic CoE is a developmental mosaic forming from different endothelial sources, and that extracardiac cells are necessary for the completion of coronary morphogenesis. These data contribute to our understanding of some coronary congenital anomalies and suggest embryonic CoE heterogeneity as an ontogenetic factor for adult coronary disease. # 471 DCM-associated RBM20-mutations lead to aberrant splicing of titin and ryanodin receptor 2 in the human myocardium {#article-title-3} Background: Mutations in human RBM20 have previously been shown to cause dilated cardiomyopathy (DCM). RBM20 is predominantly expressed in the heart. Within the nucleus it partially colocalises with other splice factors and binds RNA. Deep sequencing of the cardiac transcriptome of a human RBM20 mutant and of a RBM20 deficient rat model revealed RBM20 dependent regulation of myocardial alternative splicing. We have identified the previously published RBM20 mutation, p.P638L, which is localised in the highly conserved RS-region, in a large German family. The mutation is highly penetrant leading to terminal heart failure and/or to sudden cardiac death. Additionally we have discovered the new RBM20 mutation p.V914A localised outside the RS-region. Purpose: Though it is investigated that RBM20 is involved in alternative splicing in the rat heart little is known on aberrant myocardial splicing in human RBM20-mutation carriers. Goal of this study was to gain insight into the mechanisms leading to cardiomyopathy by analysing explanted human ventricular myocardium of RBM20-mutation carriers. Material and Methods: Cardiac tissue from two RBM20-p.P638L- and one RBM20-p.V914A-DCM-patients and a patient with the RBM20-variant p.D888N was obtained during heart transplantation or the implantation of a ventricular assist device, respectively. Ventricular myocardium was used for RNA extraction, cDNA synthesis and splicing analysis of TTN, RYR2, LDB3, CAMK2D, NEXN and TRDN by Real-Time-PCR. The alternative splicing of Titin was additionally examined by Western Blot using cardiac tissue lysates. Results: We identified aberrant RYR2 splicing in the RBM20 mutant myocardium characterised by an increased inclusion of an additional 24bp-exon. Furthermore we found a decrease of the major cardiac titin splice variant N2B by real-time PCR and Western Blot. Titin Western Blots revealed an increase of the splice variant N2BA in the RBM20 mutants. Of note, an influence on splicing could be detected not only for the RBM20-p.P638L-mutant but also for the mutation p.PV914A localised outside of the conserved RS-domain. The variant p.D888N showed no influence on the splicing of the genes analysed so far. In contrast to the rat hearts, in the human myocardium of RBM20-mutation carriers we did not find splicing defects in TRDN and NEXN. Conclusion: We present here first data on a molecular defect of a novel RBM20-mutation localised outside the conserved RS-region. Furthermore we show the influence of mutant RBM20 on splicing of RYR2 and TTN in the human explanted myocardium of three mutation carriers. The identification of the molecular pathomechanisms of the RBM20-mutations in the affected patients allows a differentiated insight into the disease mechanisms and might offer potential targets for curative treatment in the future. Furthermore the analysis of the splicing pattern helps to distinguish pathogenic variants like RBM20-p.PV914A from rare polymorphisms. # 472 The impact of missense versus nonsense mutations in arrhythmogenic cardiomyopathy phenotype {#article-title-4} Background: Arrhythmogenic Cardiomyopathy (AC) is an inherited heart muscle disease associated with mutations in five genes mainly encoding desmosomal components. Missense mutations leading to a single nucleotide substitution have disputed pathogenicity in inherited cardiomyopathies whereas truncating and splice site mutations are considered disease-causing due to their impact on form and function of the resulting protein. Purpose: Herein we describe the clinical features of two probands and their family members in whom a missense and a nonsense mutation in two desmosome-encoding genes co-segregate. Methods: A Next Generation Sequencing-based strategy comprising 150 inherited cardiomyopathy related genes was applied on the two index female cases (63y, 70y). Libraries were prepared according to the manufacturer’s instructions and sequenced on a MiSeq platform (Illumina). The Illumina Variant Studio software was used to filter and prioritize variants on the basis of genotype quality, allele frequencies, predicted pathogenicity, literature information. Subsequent conventional sequencing was used for cascade mutation screening. HL-1 cells have been transfected to ascertain localization of the mutated proteins. Results: Two unrelated female probands (63 y-old, 70 y-old) carried a missense mutation in DSG2 (p.Asn266Ser). The 63 y-old proband underwent cardiac transplantation (family A). The 70 y-old proband carried an additional nonsense mutation in DSP (c.88G>A, p.Gln113X), as well as her 64 y-old sister. Eight of the fifteen relatives from both families carried the DSG2 mutation: seven of them exhibited typical clinical AC features, whereas two young family members were unaffected at the ages of 6 and 12, respectively. The two DSP mutation carriers of family B were unaffected at the age of 44 and 66. No sudden cardiac death events occurred in both families. Haplotype analysis indicated that all the DSG2 mutation carriers shared the same haplotype suggesting a common founder allele. In vitro experiments on the cardiomyocyte cell line HL-1 showed correct localization of the mutated DSG2, whereas the mutated DSP was absent at the membrane level. Conclusions: This study is calling into question whether nonsense mutations are of high relevance with respect to the missense ones in the pathogenesis of AC. Our results highlight the dominant negative effect of a known missense DSG2 mutation with a presumed common founder effect, whereas the pathogenic role of the DSP nonsense mutation needs further studies to elucidate its contribution to the disease phenotype.

The square of ultrasound transmission velocity in a material is related to the modulus of elasticity, which is known to be an indicator of stability in bone. The aim of our study was to use ultrasound transmission velocity to obtain information about the material properties of bone tissue, keeping other factors possibly influencing ultrasound transmission as constant as possible. Apparent phalangeal ultrasound transmission velocity (APU) measured in 54 isolated, fresh pig phalanges was shown to be independent of bone mineral density (BMD) measured by SPA. Fastest sound transmission led exclusively through cortical bone so that intertrabecular connectivity in spongious bone could not influence the result. In humans APU was measured in the mediolateral direction at the midphalanx of the middle finger. In 53 healthy subjects (15–81 years old; 27 women, 26 men), there was a decrease of APU with age (r=−0.30, p

Obstruction of bile flow following pancreatoduodenectomy can be caused by stenosis of the hepaticojejunostomy created at the time of surgery, obstruction of the bile-draining jejunal loop, stones or, very rarely, ingested foreign bodies in the common hepatic duct. In analogy with endoscopic sphincterotomy or the once popular side-to-side-choledochduodenostomy, the creation of a hepaticojejunostomy eliminates the barrier of the sphincter Oddi, enabling intestinal content such as ingested foreign bodies or food fibers to migrate into the bile duct. We report on the case of a patient developing biliary tract obstruction due to fibrous material in the common hepatic duct 15 years after pancreatoduodenectomy. In addition, an overview of the literature on the rare phenomenon of foreign body-associated obstructive jaundice is given.

The main constituents of sediment samples of the river Saale were analysed by IR spectroscopy. The composition of the sediments is determined mainly by the geological conditions (increase of carbonates, decrease of clays along the stream). Anthropogenic influences on the main components were not recognized. IR spectroscopy connected with multivariate data treatment is a suitable method to determine the main components of sediments and soils presupposed that the particle size distribution of the samples is similar. A quantitative chemical analysis in terms of individual substances or substance groups is possible if a set of reference spectra can be compiled. Die Hauptbestandteile von Flus-Sedimenten der Saale wurden durch Infrarotspektroskopie analysiert. Die Zusammensetzung der Sedimente wird hauptsachlich durch die geologischen Bedingungen bestimmt (Zunahme von Carbonat, Abnahme von Tonbestandteilen in Fliesrichtung). Anthropogene Einflusse auf die Hauptbestandteile wurden nicht bemerkt. Infrarotspektroskopie ist in Verbindung mit multivariater Datenauswertung geeignet, die Hauptbestandteile von Sedimenten und Boden zu bestimmen, wenn die Teilchengrosenverteilung der Proben ahnlich ist. Eine quantitative chemische Analyse hinsichtlich individueller Stoffe oder Stoffgruppen ist moglich, wenn ein Satz von Referenzspektren zusammengestellt werden kann.

An integrated seismic reservoir characterization study is presented on data from the Yuzhno Russkoye gas field. The Upper Cretaceous reservoir sands have excellent porosities and are buried at a depth of about 1 km. The workflow includes amplitude mapping, trace classification, acoustic impedance inversions, crossplotting and reservoir modeling. Observations are calibrated with 88 wells (logs and core description). Cross plots of porosity versus acoustic impedance reveal relationships that match the log data in the blind holes rather well. Fluid contacts in the main two gas-bearing intervals coincide with flat events on seismics. Biot-Gassmann fluid replacement modeling demonstrates a consistent difference in acoustic impedance at the gas-water contact, confirmed by the inversion results. The gas-bearing reservoirs coincide with distinct bright spots. Forward modeling indicates a polarity flip near the fluid contact for the Cenomanian reservoir (AVO class 2). Sweet spots are outlined on various attribute maps. The reported gas production in the field is consistent with the reservoir inhomogeneities identified by this study. The modelling and mapping results serve as input for the shared earth model and the subsequent reservoir simulation.

Knowledge on potentially pathogenic microbes including characteristics of their antibiotic resistance in septic patients as well as on the ward- and department-specific microbial spectrum can be considered essential for an efficient initiation of an adequate antimicrobial treatment, which turns out to become pivotal for patient outcome. Permanent changes in microbial patterns and antibiotic resistance can only be identified by a continuous investigation of various microbiological specimens.Based on the retrospective evaluation of prospectively collected data on microbiological investigations of the surgical ICU in 1996, 2002, 2004 and 2005, the short- and long-term changes by trend of microbial spectrum and antibiotic resistance following reorganisation and restructuring of the University Hospital from the more traditional pavillon-based system to a multidisciplinary complex building in 2003 were investigated.Twice a week, routine microbiological testing of blood and urinary cultures as well as swabs from wound areas and endotracheal swabs were initiated in septic patients (suspect, manifestation) or in case of their clinical impairment. The microbial spectrum was sub-divided according to Gram-staining (Gram-positive/ -negative), various species and fungi with descriptive absolute and relative data values. -Various groups and time periods were statistically compared using χ² test as appropriate. P values0.05 were considered statistically significant.In total (n (Total) = 4 899), microbiological testing resulted in the detection of microbes in 699 and 833 blood and urinary cultures (14.3 % and 17 %, respectively) as well as 1 232 wound swabs (25.1 %) together with 2 135 samples from the endotracheal sites (43.6 %). During the short- (2002 vs. 2004) and long-term analyses (1996 vs. 2005), the proportion of Gram-positive microbes increased. Al-though Gram-positive bacteria can be considered the most frequent microbes for bacteriemia, there was a shift onto urinary and wound infections as well as pneumonias through the observation period. Despite the decreasing incidence of Enterococcus and the consistent proportion of MRSA, the increase of resistant Enterococcus strains (0 % vs. 43.2 %; P0.05) is critical. However, in the Gram-negative microbial spectrum there was an increase of the bacteraemia rate but a fall of the detection rate in wound and endotracheal swabs. In parallel, an increase of the detection rate of E. coli in blood (6.5 % vs. 45.5 %; P0.05) and endotracheal swabs (9.2 % vs. 16.2 %; P0.05) is associated with an increase of multiresistant Enterobacteriaceae strains (0 % vs. 30.7 %; P0.05). The portion of multiresistant strains of Pseudomonas with 31 % stayed the same through the 10-year time period. While Candida-based colonisation showed a decreased incidence (25 % vs. 15 %; P0.05) during the whole investigation period, there was a relative rise in the frequency of candidemia.ICU relocation from the pavillon-based system to a new complex clinic building was not associated with any significant alteration of the microbial spectrum on the surgical ICU. Increasing incidences of resistant Enterococcus and Gram-negative problematic microbes may indicate a general spread of multi-resistant microbes under the steady selecting pressure of a not always adequately initiated antibiotic / antimicrobial therapeutic regimen and underline the required but specific and selected microbiological screening.

Erroneous tokens in the output of an OCR engine can be roughly divided into two categories. For less serious OCR errors typically human readers - in many cases also text correction systems - are able to reconstruct the correct original word, or to suggest a small set of plausible corrections. Sometimes, however, the OCR output contains "garbage" output tokens for which it is completely impossible to predict the correct word. Garbage tokens are for example caused by graphics occurring in images misinterpreted as text by the OCR engine. In this paper we report on the development of a classifier for garbage tokens in OCR output on historical documents. The classifier is based on a specific feature set and implemented as a support vector machine. In our experiments it clearly outperformed simple rule-based predecessor solutions for OCR garbage detection.

The square of ultrasound transmission velocity in a material is correlated to the modulus of elasticity, which is an indicator of its mechanical properties. This might make the measurement of ultrasound transmission velocity useful in the noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic material but is architecturally structured. The aim of our study was to investigate and especially to quantify the influence of architecture in cortical bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound transmission velocity was measured parallel and perpendicular to direction of Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/- 29 m/s perpendicular to Haversian channels respectively (p0.001). Our results clearly indicate that there is an important influence of architecture in cortical bone on ultrasound transmission velocity which has to be taken into account in its clinical use.

Starting from oxalate mixed crystals NixMn3−x(C2O4)3·6H2O thermal decomposition at reduced oxygen partial pressure (po2= 2%) leads to the formation of NiMn2O4 (x = 1) at metastable conditions. Ni1.5Mn1.5O4 (x = 1.5) existing in the metastable state only has been also prepared. The spinel compounds both are of the highly inversed type. Following a sol-gel preparation route Mg2TiO4 has been also found to be formed in the metastable state. Annealing results in decomposition of the compounds providing NiMnO3 and 1/2α-Mn2O3 or NiMnO3 only or MgTiO3 and MgO, respectively. The reaction rates observed are lower for NiMn2O4 and Ni1.5Mn1.5O4 than for Mg2TiO4 decomposition. The reverse reaction of NiMn2O4 formation above 730°C shows an endothermic enthalpy of +61 kJ·mol−1. For Mg2TiO4 formation above 1050°C an endothermic enthalpy of +19.3 kJ·mol−1 is found. The results are discussed in terms of structural features of the oxides.

worldwide, orthotopic heart transplantation (HTx)remains an accepted therapeutic option in the treatment ofheart failure. As cardiac transplantation evolved, malignantdisorders in the postoperative course became a seriouscomplication after solid organ transplantation. With im-proved survival, the first reports on postoperative lympho-proliferative disorders

Under inflammatory conditions, the pleiotropic cytokine interleukin-10 (IL-10) is released in many tissues. It mediates anti-inflammatory effects in particular by inhibiting the release of T helper type 1 (Th1) cytokines. In contrast, we show here that NK cell cytotoxicity against autologous macrophages is elevated if both cell types are cultured with IL-10. The expression of most activatory NK receptors is increased after culture in the presence of IL-10. On the other hand, macrophages cultured in the presence of IL-10 show elevated expression of the NKG2D ligands major histocompatibility complex (MHC) class 1-like molecules (MIC) - A and - B, as well as UL-16 binding proteins (ULBP) - ULBP-1, ULBP-2 and ULBP-3. By masking the interaction of NK cells with macrophages through interruption of the NKG2D receptor with its ligands, we could reverse the IL-10-induced lysis of macrophages. Our data therefore reveal that IL-10 may exert a novel immunomodulatory role by stimulating NKG2D ligand expression on macrophages, thereby rendering them susceptible to NK cell elimination. This suggests that NK cells would delete macrophages and potentially other immature antigen-presenting cells (APC) or their precursors under inflammatory conditions as a feedback mechanism to shut off uncontrolled immune responses.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

Retroperitoneal soft-tissue sarcomas (RSTS) represent a rare and heterogeneous class of diseases for which the clinical management is still largely non-standardised. Based on a selective review of recent publications, it was the purpose of the present review article to summarize the current concepts of disease classification, diagnostics and surgical as well as multimodal therapy for these tumors.A clinically based empirical review derived from a literature search focusing on publications from the past 5 years was carried out.Due to the paucity of randomised-controlled trials, therapy for RSTS is largely based on personal experience, retrospectively gathered data and historical controls. Pre-therapeutic planning requires precise information on the localisation, extension, and texture of the tumor through cross-sectional imaging (CT, MRI) as well as histological diagnosis through percutaneous or open biopsy. Complete tumor resection is crucial. Recent studies have confirmed the importance of microscopically negative resection margins which has subsequently led to a trend towards more radical resection. Chemotherapy does not play a role in the adjuvant setting except in clinical trials; however, radiotherapy has been controversely debated in adjuvant RSTS therapy. Efforts to limit radiation toxicity include modern techniques as well as a strategy of using pre-resection radiotherapy instead of postoperative radiation. Surgery is also the treatment of choice for locally recurrent RSTS and pulmonary metastases. The prognosis of RSTS depends on the quality of surgical care and several disease-specific factors (histological type, grading).The clinical management of RSTS is complex and can only partly be considered as evidence-based. Due to the required level of experience in the treatment of these tumor lesions and the involvement of several subspecialties, pre-therapeutic planning, treatment and follow-up should be limited to high-volume surgical centres. In order to achieve microscopically negative resection margins, multivisceral resections are a valuable option after thorough consideration of the risks and benefits. Adjuvant radiotherapy needs to be decided upon on an individual basis, taking into account patient- and tumor-specific factors as well as resection status.

This study was a pre-planned country-specific secondary analysis of results in Germany from a multinational multicenter observational study to retrospectively evaluate clinical outcomes with caspofungin in patients with probable and proven invasive fungal infection following solid organ transplantation (SOT).Data were retrospectively collected on a single episode of invasive fungal infection (IFI) in patients who had a SOT between January 2004 and June 2007. Effectiveness was reported as the proportion of patients who received at least five doses of caspofungin with a favorable (complete or partial) response. Safety was assessed for patients who received at least one dose of caspofungin. Descriptive statistics were employed for all evaluations.A total of 41 SOT patients (27 male, 14 female; median age 56 years, median APACHE II score at start of caspofungin therapy 23) were enrolled from 5 sites in Germany. Organs transplanted were mainly heart (51%) and liver (46%). Prevalent risk factors for IFI at baseline were use of central venous catheter (37 out of 41 patients, 90%), steroid use (37 out of 41 patients, 90%), recent stay in intensive care (36 out of 41 patients, 88%),and duration of SOT procedure5 hours (21 out of 41 patients, 51%). Candidiasis was diagnosed in 34 patients (83%) and aspergillosis in 10 patients (24%). The lungs were the most common site of IFI (21 out of 41, 51%). Caspofungin as monotherapy was received by 28 patients (68%); 6 patients (15%) received caspofungin as salvage therapy for IFI, in most cases because they were refractory to prior antifungal drugs. Immunosuppressants were administered with caspofungin in 39 out of 41 patients (95%). In subjects with at least 5 doses of caspofungin (modified intention to treat population) the favorable response rate at the end of caspofungin therapy was 88% overall, 29 out of 33 patients; 95% confidence interval (95%-CI) 72-97%), 86% (19 out of 22 patients) with monotherapy and 91% (10 out of 11 patients) with combination therapy. No (serious) adverse events or drug interactions related to treatment with caspofungin were reported. The overall survival rate was 79% (26 out of 33 patients; 95%-CI 61-91%) at 7 days after completion of caspofungin treatment.Caspofungin was found to be an effective treatment of probable and proven invasive fungal infections in patients following SOT in Germany.

M. Winkler, J. Pratschke, U. Schulz, S. Zheng, M. Zhang, W. Li, M. Lu, D. Sgarabotto, G. Sganga, P. Kaskel, S. Chandwani, L. Ma, J. Petrovic, M. Shivaprakash. Caspofungin for post solid organ transplant invasive fungal disease: results of a retrospective observational study. Transpl Infect Dis 2010: 12: 230–237. All rights reserved Objective This study was designed to determine clinical outcomes with caspofungin in patients with proven or probable invasive fungal infection (IFI) after a solid organ transplant (SOT) procedure. Methods In this retrospective observational study, data were collected for a single episode of IFI in patients with an SOT between January 2004 and June 2007. Response was determined by the investigator as favorable (complete or partial) or unfavorable (stable disease or failure) at the end of caspofungin therapy (EOCT). The primary effectiveness population was the proportion of patients who received ≥5 doses of caspofungin (modified all-patients-treated population). Safety was assessed for patients who received ≥1 dose of caspofungin. Results A total 81 of patients from 13 sites in China, Germany, Italy, and the United Kingdom were enrolled, including 49 (60%) liver, 22 (27%) heart, 5 (6%) lung, 2 (2%) kidney, 2 (2%) liver and kidney, and 1 (1%) pancreas and kidney recipients. Candidiasis was diagnosed in 64/81 patients (79%) and aspergillosis in 22/81 patients (27%). Most patients received caspofungin monotherapy (75%). Caspofungin was given as first-line therapy to 59 (73%) patients. The overall favorable response at EOCT was 87% (58/67; 95% confidence interval [CI]: 76%, 94%), with favorable responses in 88% (43/49; 95% CI: 75%, 95%) of patients receiving caspofungin monotherapy and 83% (15/18; 95% CI: 59%, 96%) of patients receiving combination therapy with caspofungin (modified all-patients-treated population). Response by type of SOT was as follows: liver 87% (39/45), heart 93% (14/15), kidney 100% (5/5), and lung 50% (2/4). An overall survival rate (all-patients-treated) of 69% (56/81; 95% CI: 59%, 79%) was observed at 7 days post EOCT. No serious drug-related adverse events were reported. Conclusion In this study, caspofungin was effective and well tolerated in the treatment of IFIs involving SOT recipients.

A high-performance liquid chromatographic method for the determination of low concentrations in serum of apovincaminic acid, the main metabolite of vinpocetine, is reported. The assay includes a two-step ion-pair extraction with tetrabutylammonium as counter ion. Recovery is ca. 40%. Separation is performed on a narrow-range 5 microns particle size octadecylsilane modified silica packing. Heptanesulphonic acid is the pairing ion in the eluent, and the ultraviolet detection wavelength is 224 nm. Yohimbine serves as the internal standard. The assay is fast, accurate and sensitive quantifying at least 5 ng/ml apovincaminic acid in serum. The method was applied to the analysis of serum samples from aged subjects, treated with a 20-mg dose of vinpocetine.

At the Heart Center North Rhine-Westfalia, Germany, more than 1,500 adult cardiac transplantations and more than 100 pediatric cardiac transplantations have been performed since the transplant program was initiated in 1989. Each year, we take care of 800 cardiac transplant recipients and 1,700 patients with heart failure who are in a long-term program for cardiac transplantation or on the Eurotransplant waiting list for cardiac transplantation. We have experience with ventricular assist device implantation as bridge to transplant in more than 300 patients. In total, our clinical know-how with cardiac transplant recipients is based on 10,800 patient-years of observation. In 2006, we transplanted the first donor heart worldwide with the Organ Care System, a technology capable of maintaining human organs in a functioning state ex-vivo. Usually, our transplant recipients have more preoperative risk factors than cardiac transplant recipients at other German heart centers. Our postoperative patient care is individualized with respect to immunosuppression and the performance of myocardial biopsies and coronary angiography. Since 1989, we have performed 31 cardiac retransplantations.

Blutdruck, Mimik und mimische Interaktion wurden bei jeweils acht Hypo-, Normo- und Grenzwerthypertonikern wahrend eines streβ-induzierenden Gespraches kontinuierlich erfaβt. Situativer Blutdruckanstieg war als Streβindikator, Blutdruckgrup-penzugehorigkeit als Indikator eines chronischen Streβbewaltigungs-stils konzipiert. Im Rahmen der unterschiedlichen Bewaltigungsstile wurden auch Unterschiede in Mimik und mimischer Interaktion erwartet. Die Ergebnisse zeigen, daβ Grenzwerthypertoniker unter starkem Streβ mimisch erstarren und daβ sie insgesamt ein kleines mimisches Repertoire aufweisen. Hypotoniker zeigten die groβte mimische Vielfalt. Hypo-, Normo- und Grenzwerthypertoniker wurden von Interview-erinnen mimisch unterschiedlich «behandelt»: Die Grenzwerthypertoniker sahen sich insbesondere dann, wenn sie stark gestreβt waren, einer «mimisch abweisenden» Gesprachspartnerin gegenuber.

Corynebacterium pseudotuberculosis is the causative organisms of caseous lymphadenitis (pseudotuberculosis) in sheep and goats (Lloyd et al. 1990; Lindsay and Lloyd 1991). This condition is characterized by abscessation of one or more lymph nodes, but sometimes presents as pneumonia, hepatitis, mastitis, arthritis, orchitis and subcutaneous abscesses. Corynebacterium pseudotuberculosis is associated with lymphadenitis in horses and ulcerative lymphangitis in cattle (Sutherland et al. 1993; Aleman et al. 1996; Miers and Ley 1980) and affects rarely in human beings (Peel et al. 1997). Pseudotuberculosis occurs worldwide and it has also been described in camels in several countries (Wernery and Kaaden 2002). Two biotypes of C. pseudotuberculosis, based on nitrate-reducing ability, have been reported and these biotypes can be correlated with different genotype patterns (Songer et al. 1988; Sutherland et al. 1996). Isolates from sheep and goats were nitrate negative whereas those from horses were nitrate positive. Reactions from cattle isolates were variable. Strains that reduce nitrate are referred as biotype equi and strains that fail to do so are referred as biotype ovis. Barakat et al. (1984) found two serotypes referred as type I and type II which corresponded with nitrate reductase negative and positive strains, respectively. In camels, only the serotype I (biotype ovis) has been described in the available literature (Wernery and Kaaden 2002). A study on pseudotuberculosis in camels was carried out in the Canary Islands, using 13 affected dromedaries, and isolating C. pseudotuberculosis biotype ovis in all cases (Tejedor et al. 2004). This communication presents the isolation of Corynebacterium pseudotuberculosis nitrate reductase positive from two camels belonging to the same herd and located in Canaries.

Nanostrukturen mit reflexmindernden Eigenschaften konnen durch Plasmabehandlung auf vielfaltigen Polymeren erzeugt werden. Eine noppenartige Struktur mit ausgezeichneten optischen Eigenschaften entsteht auf PMMA vollig selbstorganisierend. Auf vielen anderen Materialien wie Polycarbonat und Zeonex oder auch Polymerlacken kann eine schwammartige Strukturbildung durch das vorherige Abscheiden einer sehr dunnen Schicht initiiert werden. Auch diese Oberflachen erreichen hohe Transmissionswerte und lassen sich besser als die noppenartige Struktur mechanisch stabilisieren. Von grosem praktischem Interesse sind auserdem Antibeschlag- Eigenschaften, die auf den entspiegelten Oberflachen durch das Aufbringen hydrophiler Oxidschichten erreicht werden. Plastic optics exhibiting anti-reflection and anti-fogging properties produced by plasma etching and coating Plasma treatments are capable to generate antireflective surface structures on various polymers. On PMMA a self organized surface with nep-like bumps exhibits excellent optical properties. Many other materials like polycarbonate, zeonex and lacquers can be etched after depositing a very thin initial layer to form a more holey structure. These surfaces attain high transmission values too and can be better stabilized by coatings than the nep- structure on PMMA. Interesting for practical applications are hydrophilic top-layers to provide anti-fogging properties in combination with improved transmission.

Most systems for correcting errors in texts make use of specific word distance measures such as the Levenshtein distance. In many experiments it has been shown that correction accuracy is improved when using edit weights that depend on the particular symbols of the edit operation. However, most proposed approaches so far rely on high amounts of training data where errors and their corrections are collected. In practice, the preparation of suitable ground truth data is often too costly, which means that uniform edit costs are used. In this paper we evaluate approaches for deriving symbol dependent edit weights that do not need any ground truth training data, comparing them with methods based on ground truth training. We suggest a new approach where special error dictionaries are used to estimate weights. The method is simple and very efficient, needing one pass of the document to be corrected. Our experiments with different OCR systems and textual data show that the method consistently improves correction accuracy in a significant way, often leading to results comparable to those achieved with ground truth training.

Metacarpophalangeal flexion of the thumb is known to be highly variable. To obtain normative values, active metacarpophalangeal flexion of the thumb was measured bilaterally in healthy Caucasian adults (female n = 403; male n = 366) in a standardized manner. Independent of gender, inter-individual variation was high, ranging between 16 degrees and 90 degrees and showing a continuous decrease with increasing age. Women showed a bigger range of motion than men but in both range of motion was higher on the left thumb (mean 1.4 degrees in women and mean 1.1 degrees in men). No influence of hand dominance was observed. Thus, the healthy contralateral side should be used as parameter of comparison.