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The intake of omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), is associated with health benefits due to its anti-inflammatory properties. This fatty acid also exhibits antifungal properties in vitro. In order to determine if this antifungal property is valid in vivo, we examined how EPA affects Candidaalbicans pathogenesis in the Caenorhabditiselegans infection model, an alternative to mammalian host models. The nematodes were supplemented with EPA prior to infection, and the influence of EPA on C.elegans lipid metabolism, survival and immune response was studied. In addition, the influence of EPA on hyphal formation in C.albicans was investigated. It was discovered that EPA supplementation changed the lipid composition, but not the unsaturation index of C.elegans by regulating genes involved in fatty acid and eicosanoid production. EPA supplementation also delayed killing of C.elegans by C.albicans due to the inhibition of hyphal formation in vivo, via the action of the eicosanoid metabolite of EPA, 17,18-epoxyeicosatetraenoic acid. Moreover, EPA supplementation also caused differential expression of biofilm-related gene expression in C.albicans and stimulated the immune response of C.elegans. This provides a link between EPA and host susceptibility to microbial infection in this model. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the characteristics of asylum-seeking children with medical complexity visiting a tertiary care hospital in Switzerland, detailing their underlying medical conditions and management. Asylum-seeking patients with frequent visits between January 2016 and December 2017 were identified using administrative and electronic health records. Of 462 patients, 19 (4%) fulfilled the inclusion criteria with 811 (45%) visits. The age of the 19 patients ranged from 0 to 16.7 years (median of 7 years) with two main age groups identified: < 2 years and > 12 years. Nine (47%) patients originated from Syria. A total of 34/811(4%) visits were hospital admissions, 66/811 (8%) emergency department visits and 320/811(39%) outpatient department visits. In children < 2 years genetic diseases (5/8; 63%) and nutritional problems (6/8; 75%) were most common; in adolescents, orthopedic diseases (4/8; 50%) and mental health problems (4/8; 50%). Asylum-seeking children with medical complexity represent a small but important group of patients requiring frequent medical consultations. The high proportion of young patients with genetic diseases and severe nutritional problems suggests that new strategies are required in the management of this specific group of asylum-seeking children. This could be achieved by improved co-ordination between hospital and non-hospital care exploring options for integrated care. [ABSTRACT FROM AUTHOR]

The use of volatile anaesthetics in intensive care medicine has so far been limited by the lack of equipment suitable for daily routine use and the need for an anaesthetic machine. The new Anaesthetic Conserving Device (AnaConDa) enables the routine use of volatile anaesthetics for long-term sedation via intensive care ventilators. The Anaesthetic Conserving Device replaces the common heat and moisture exchanger in the ventilation circuit. The volatile anaesthetic is continuously applied in liquid status via a syringe pump to a form of mini-vaporiser where the anaesthetic agent is vaporised. The expired anaesthetic gas is stored in the carbon filter and approximately 90% of the gas is resupplied into the breathing cycle. The current experiences suggest that volatile anaesthetics present an alternative for long-term sedation in intensive care units, providing optimised pathways, from a medical as well as from an economical point of view. It must, however, be emphasized that the use of volatile anaesthetics for longer periods of time is an off-label use and should only undertaken by medical professionals at their own risk. [ABSTRACT FROM AUTHOR]

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Introduction: Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. Methods: One hundred thirty-five relapsing–remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. Results: A significant atrophy occurred over 6 months (PBVC = −0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions ( p = 0.024), the on-study Gd-enhancing lesion volume ( p = 0.044), and the number of on-study PBHs ( p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. Conclusion: Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power. [ABSTRACT FROM AUTHOR]

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Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method to investigate changes in brain metabolite composition in different cerebral diseases. We performed proton spectroscopy in patients with dementia of the Alzheimer's type (AD) and in patients with motor neuron disease (MND) with the aim to detect the specific metabolic pattern for these neurodegenerative disorders. In the MND group we found a significant reduction of NAA/tCr metabolite ratios in the motor cortex, which correlates with the disease severity and the clinical lateralization of neurological symptoms and further decreases in the time course of the disease. In AD patients a reduction of NAA/tCr was observed in the medial temporal lobe. Since NAA is exclusively expressed in neurons as shown by immunohistochemical studies, reduced NAA levels suggest neuronal loss or dysfunction in the observed regions. The observed regional metabolic alterations reflect the neuronal basis of the characteristic neurological symptoms in AD (dementia) and MND (muscular palsy) and mirrors the disease progress over time. [ABSTRACT FROM AUTHOR]

Seawater samples for a laboratory intercomparison of trace metal concentrations (Mn, Fe, Ni, Cu, Cd, Pb) in the dissolved (<0.4 µm filtered) and particle-bound phases as well as total and reactive Hg were collected in the Gotland Basin, a region in the Baltic Sea with trace metal gradients in the halocline and the redox boundary. Two laboratories took part in this exercise, each laboratory analysing samples from two vertical profiles collected using ”clean” sampling techniques. The hydrographic and hydrochemical situation was determined to characterise the water column and help interpret the results. An estimation of the conformity of the two laboratories was performed by comparing the results with international intercalibration exercises and certified reference materials. For all metals the characteristic vertical distribution and the concentration range of the data were comparable to other results published for the region. The concentration differences in the amount contents of Mn, Fe, Ni, Cu, Cd, Pb and Hg determined between both laboratories were better than the confidence intervals given by an ICES (International Council for the Exploration of the Sea) international comparison exercise for Baltic waters. Differences for Ni in the anoxic water body are attributed to the sulphidic matrix and their influence on the different methods used by the laboratories. For Pb and Hg the concentrations were near the detection limit of our methods, low level contamination was possibly responsible for the concentration differences. Small differences for dissolved Mn were attributed to different sampling techniques. We conclude that sampling and sample handling are still weak links in the trace metal analysis of anoxic seawater and that the analytical methods we used for this exercise are satisfactory for the accurate determination of Cd, Cu, Pb, Mn, Fe, and also for studying biogeochemical cycling of these trace metals in oxygen-rich and anoxic water bodies. [ABSTRACT FROM AUTHOR]

T cells can be directed to antigen-specific, MHC-independent target ceil lysis by grafting with a recombinant receptor with antibody-like specificity. Here, we asked whether T cells from the peripheral blood of a patient with cutaneous T cell lymphoma can be recruited for an immune response against autologous tumor cells. Lymphoma cells with a CD3[sup -] CD4[sup +] CD30[sup +] phenotype and clonal TCR-Vβ7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3[sup +] CD25[sup +] activated normal T cells despite ongoing tumor progression. Peripheral blood-derived T cells from the lymphoma patient were retrovirally engrafted with a recombinant anti-CD30scFv-γ receptor. Upon cocultivation with autologous CD30[sup +] lymphoma cells, grafted T cells increase IFN-γ secretion and lyse specifically lymphoma cells with high efficiency, even at an effector to target cell ratio of as low as 1:20. Our data demonstrate that the recombinant anti-CD30-γ receptor overcomes T cell tolerance for tumor cells and directs T cells specifically against autologous lymphoma cells. [ABSTRACT FROM AUTHOR]

T cells can be endowed with antigen specificity by grafting with a chimeric receptor consisting of an extracellular antigen binding moiety (scFv) derived from an antibody and an intracellular signaling domain. Conflicting data exist on the impact of an extracellular spacer domain between the antigen binding and the signaling domain with respect to cellular activation. Here, we recorded conjugate formation and antigen-driven cellular activation of T cells grafted with receptor molecules that contain the same antigen binding site (antiCD30 HRS3-scFv) and signaling domain (Fc∈RI γ-chain), however, with and without an IgG1 CH2CH3 (Fc) spacer domain between the scFv and transmembrane moiety. Receptors of both configurations mediate equally efficient conjugate formation between receptor grafted T cells and antigen-positive target cells. Specific signaling by the spacer containing receptor, however, is blocked by five- to 10-fold lower concentrations of soluble antigen than by the spacerless receptor indicating a higher avidity of the spacer containing receptor to soluble antigen. In contrast, cellular activation upon binding to antigen-positive cells is mediated more efficiently by the spacer-less receptor. This demonstrates that the extracellular spacer domain impairs antigen-dependent cellular activation by the chimeric immune receptor, but not intercellular conjugate formation. [ABSTRACT FROM AUTHOR]

We report the case of a 55-year-old man who developed heparin-induced thrombocytopenia II after a vertebral fracture. Autopsy revealed segmental hepatic vein thrombosis of the right lobe with subacute congestion and an activation of hepatic stellate cells. This case shows that heparin-induced thrombocytopenia II is a possible cause of the Budd-Chiari syndrome. [ABSTRACT FROM AUTHOR]

Chimeric T cell receptors with specificity for tumor-associated antigens are successfully used to target T cells to tumor cells. The efficacy of this approach, however, is reduced by soluble antigen that is frequently present in high serum concentrations. To overcome this situation, we constructed an anti-CEA chimeric receptor whose extracellular moiety is composed of a humanized single chain antibody fragment (scFv) derived from the anti-CEA mAb BW431/26 and the CH2/CH3 constant domains of human IgG. The intracellular moiety consists of the γ-signaling chain of the human FcεRI receptor constituting a com- pletely humanized chimeric receptor. After transfection, the humBW431/26 scFv-CH2CH3-γ receptor is expressed as a homodimer on the surface of MD45 T cells. Co-incubation with CEA+ tumor cells specifically activates grafted MD45 T cells indicated by IL-2 secretion and cytolytic activity against CEA+ tumor cells. Notably, the efficacy of receptor-mediated activation is not affected by soluble CEA up to 25 μg/ml demonstrating the usefulness of this chimeric receptor for specific cellular activation by membrane-bound CEA even in the presence of high concentrations of CEA, as found in patients during progression of the disease. [ABSTRACT FROM AUTHOR]

The aim of this intercomparison exercise was to assess the comparability of trace metal analyses of blank filters and of marine suspended particulate matter (SPM) on filters performed by laboratories in ICES member countries. Fifteen experts from the United Kingdom, Canada, France, Germany, the Netherlands, Norway, Poland, Russia, and the United States were invited to participate in this exercise for trace metal analyses of Cu, Pb, Zn, Cd, Al, Li, Fe, Mn, Ni and Co (tentative) in SPM. Each filter analysed in this project was an individual sample, the absolute loadings on the filters varying from 0.8 to 2 mg of SPM. The inter-laboratory means and the relative standard deviations (RSD) from the grand mean for the metals determined were: Al 67.5 mg/g, 8.3%, Fe 51.7 mg/g, 10.9%, Cd 1.5 μg/g, 22.7%, Cu 39 μg/g, 13.3%, Pb 38 μg/g, 34.7%, Mn 1060 μg/g, 13%, Ni 49.2 μg/g, 29%, Zn 182 μg/g, 32.5%, Li 52.8 μg/g, 26.1%, Co 15.4 μg/g, 23.6%. In general, the exercise demonstrated that it is possible for the various participants to collect very small amounts of SPM and analyse it by the different determination techniques. Compared to earlier exercises, comparability between laboratories was still difficult to achieve and limited. [ABSTRACT FROM AUTHOR]

In 76 curative resected advanced gastric carcinomas, the relationships between macro- and microscopy of the carcinoma and the survival rate were studied by univariate and multivariate survival analyses. In the Kaplan-Meier survival analysis (product limit estimator), significant influence on survival rate was found for tumor size, Laurén type, number of lymphocytes, tumor fibrosis, and N stage. In the multivariate survival analysis of covariates according to the Cox regression model, in macroscopically evaluable variables the tumor size was effective, in bioptically evaluable variables the number of plasma cells and the histological type. Concerning the primary tumor, the same set of variables presents significant correlations to survival time. Adding the involvement of lymph nodes, Laurén type, and N stage express all significant correlations of the tumor to survival rate. In parametric multivariate stepwise regression analyses of survival time, all variables working in the Cox proportional hazard model were very ineffective. But adaption of the Kaplan-Meier test to the effective variables of multivariate survival analysis elucidates the tight relationships between survival rate and these variables. No distinct relationships are present between variables of primary tumor and presence of lymph nodes metastases or N stage respectively. [ABSTRACT FROM AUTHOR]

Three different antisera against human prostatic acid phosphatase were used for direct and indirect immunohistochemical demonstration of acid phosphatase in paraffin sections of infantile and adult normal, hyperplastic and carcinomatous prostatic tissue. All antisera were prepared in rabbits. Antiserum A was prepared from highly purified acid phosphatase extracted from autopsy specimens. Antiserum B was a concentrate of a commercial antiserum used in radioimmunoassay and was prepared from purified extracts of human seminal fluid. Antiserum C was a peroxidaseconjugated antiserum prepared from purified extracts of human seminal fluid. The specificity of the three antisera was compared using different immunohistochemical methods and tissues. It was comparably high in all three antisera which gave only slightly different staining results in prostatic tissue. The staining results in prostatic carcinoma were only dependent on the titer of the respective antiserum. Carcinomas with a cribriform growth pattern showed variable staining, but always had a positive immunoreaction, provided the titer of the antiserum was sufficiently high. Striking differences were observed in metaplastic, atrophic and hyperplastic prostatic epithelium. The most intense reaction was observed in atrophic glands; it was much less intense in hyperplastic and normal epithelium and negative or slightly positive in metaplastic epithelium. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The functional polymorphism methionine synthase (MTR) c.2756A > G (D919G) has been reported to modify the risk of vascular disease and to promote disease-free longevity. In 714 individuals from 187 families, blood pressure was measured, antihypertensive medication recorded and MTR genotype determined. A significant association of the MTR polymorphism with diastolic blood pressure was found which might explain the beneficial effects of its G-allele on vascular disease and disease-free longevity and could be a basis for novel antihypertensive strategies. [ABSTRACT FROM AUTHOR]

Copyright of Langenbecks Archiv fuer Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Langenbecks Archiv fuer Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The main factors influencing the distribution patterns of material discharged by the river Oder into the Pomeranian Bight are : - the pulsating character of the outflow ('outflow events'); - the physical distribution and mixing of the material by wind controlled currents in the bight; - the modification of the material by biological, physical and chemical processes. Due to the independent action of these factors, the distribution patterns are highly variable. In the TRUMP-project running from 1993 to 1996, the fate of the Oder plume was investigated during seven multi-ship cruises, some of them in co-operation with Polish institutes. A short summary of the results is given here describing 'normal conditions' in the Pomeranian Bight before the flood event in summer 1997. The regional distribution of Oder discharges in the Pomeranian Bight and Baltic Sea is controlled by physical transport and mixing. As the wind is the driving force for the development of currents in this area, two situations are of special interest : the 'west wind situation' and the 'east wind situation'. In both cases, the discontinuous outflow of material can be followed in subsequent distribution patterns. Because biological processes are negligible during winter, this season is characterized by significant correlations between salinity and nutrient salts. However, mixing is not the only mechanism that generates concentration gradients. A variety of additional factors, which are influenced by seasonal variations, affect the distribution of individual species of the discharged material: - variations in the runoff of the river Oder; - (biological, physical and chemical) processes in the Stettin lagoon and in the lagoon of Greifswald; - (biological, physical and chemical) processes in the Pomeranian Bight. Due to the interplay of these effects, the amounts of riverine material in the Pomeranian Bight are highly variable. Concentrations of nutrient salts may change by nearly one order of magnitude within a few days or within a distance of a few miles. For other substances, e.g. DOC, variations are less pronounced, probably due to a higher background concentration in the Baltic Sea. As a consequence of modification processes in the lagoons, concentrations of individual species of the riverine material are not related to each other and thus may strongly influence other processes in the bight, e.g. generating limitating conditions for primary production or affecting transport mechanisms of some trace metals. On the background of the knowledge gained during the TRUMP-project and by the HELCOM monitoring program, it has to be stated that concentrations for most compounds analyzed during the Oder flood in summer 1997 are in a 'normal' range. Exceptionally high concentrations had only been found for organic carbon and organic nitrogen and for silicate. [ABSTRACT FROM AUTHOR]