[Patient reported outcome measures in public reporting : Objectification of quality information via physicians and hospitals]. / "Patient reported outcome measures" in der öffentlichen Berichterstattung : Objektivierung von Qualitätsangaben über Ärzte und Krankenhäuser.

Patient reported outcome measures (PROM) are considered a good method of measuring the results of treatment outcomes with the aim of improving the functional, cognitive and mental state of patients and the quality of life during and after treatment. The publication of these results serves the patient's interest in finding the best provider for a treatment. The existing interest of many service providers for the integration of electronic PROM into everyday clinical practice is often faced by barriers due to financial, personnel and technical factors. This must be eliminated in the interest of patient information in order to facilitate the rapid introduction of this patient-centered treatment outcome measurement into as many hospitals and specialist departments as possible.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Phenotypic and genotypic methods for typing Campylobacter jejuni and Campylobacter coli in poultry.

Human campylobacteriosis, an infection caused by the bacterium Campylobacter, is a major issue in the United States food system, especially for poultry products. According to the Center for Disease Control, campylobacterosis is estimated to affect over 2.4 million people annually. Campylobacter jejuni and Campylobacter coli are 2 species responsible for the majority of campylobacterosis infections. Phenotypic and genotypic typing methods are often used to discriminate between bacteria at the species and subspecies level and are often used to identify pathogenic organisms, such as C. jejuni and C. coli. This review describes the design as well as advantages and disadvantages for 3 current phenotypic techniques (biotyping, serotyping, and multilocus enzyme electrophoresis) and 6 genotypic techniques (multilocus sequence typing, PCR, pulse-field gel electrophoresis, ribotyping, flagellin typing, and amplified fragment length polymorphisms) for typing pathogenic Campylobacter spp.

Evaluating 3 gas-delivery systems for culturing Campylobacter jejuni in a microaerophilic environment.

Campylobacter spp. require a microaerophilic environment (80% N(2), 10% CO(2), 5% H(2), and 5% O(2)) for growth. Since the late 1800s, several systems for creating and maintaining specific microbial atmospheres have been developed and applied. The objective of this study was to evaluate Campylobacter jejuni growth by means of 3 commonly used gas-delivery systems for generating a microaerophilic environment: automated, gas-generating sachet, and plastic storage bag. Pure culture C. jejuni cells were suspended in Brucella broth and spread onto campy cefex agar plates. For the automated gas-delivery system, plates were positioned in a Mart anaerobic jar and flushed with a microaerophilic gas mixture using an Anoxomat Mart II system (Mart Microbiology B. V., Netherlands). For the sachet samples, plates were placed in a Mart anaerobic jar and 3 Gaspak EZ campy sachets (Becton Dickinson and Company, Franklin Lakes, NJ) were activated to induce a microaerophilic gas environment. The plates placed in plastic storage bags were flushed with a microaerophilic gas mixture from a premixed tank. For all 3 systems, plates were placed in a low-temperature incubator at 42°C for 24 h. After 24 h, plates were removed from the incubator and colonies were counted. The entire experiment was repeated 5 times. Results indicated no significant difference in colony counts among the gas-delivery systems tested, but colonies grown under the sachet-generated environment were smaller than colonies in the other 2 methods. Smaller colonies could have resulted from the type of media used or the length of time the plates were incubated. In conclusion, all 3 gas-delivery methods were able to produce similar Campylobacter growth results. Initial and long-term costs of equipment, as well as laboratory space availability, may be influential when choosing a gas-delivery method for generating a microaerophilic environment.

Paralysis and early death in cysteine string protein mutants of Drosophila.

Multimeric complexes of synaptic vesicle and terminal membrane proteins are important components of the neurotransmitter release mechanism. The csp gene of Drosophila encodes proteins homologous to synaptic vesicle proteins in Torpedo. Monoclonal antibodies demonstrate different distributions of isoforms at distinct subsets of terminals. Deletion of the csp gene in Drosophila causes a temperature-sensitive block of synaptic transmission, followed by paralysis and premature death.

Presynaptic dysfunction in Drosophila csp mutants.

Cysteine string proteins are synapse-specific proteins. In Drosophila, csp deletion mutants exhibit temperature-sensitive paralysis and early death. Here, we report that neuromuscular transmission is impaired presynaptically in these csp mutant larvae. At 22 degrees C, evoked transmitter release is depressed relative to wild type and rescued controls, and high frequency stimulation of the nerve leads to sporadic failures. At 30 degrees C, stimulus-evoked responses decline gradually before failing completely. When the temperature is returned to 22 degrees C, evoked responses recover. Spontaneous release events persist at both 22 degrees C and 30 degrees C. Since nerve conduction and postsynaptic sensitivity are unaffected, these data indicate that csp mutations disrupt depolarization-secretion coupling. This disruption explains the cellular basis of the temperature-sensitive paralysis of these organisms.

Overcoming the resistance of codling moth against conventional Cydia pomonella granulovirus (CpGV-M) by a new isolate CpGV-I12.

Recently, codling moth (CM, Cydia pomonella L.) populations with a significantly reduced susceptibility to C. pomonella granulovirus (CpGV) products have been observed in Germany. A novel CpGV isolate, designated CpGV-I12, is able to overcome the CpGV resistance. CpGV-I12 originated from Iran and showed superior efficacy in laboratory bioassays against a resistant CM strain (CpR), which has a 100-fold reduced susceptibility to commercially used isolate CpGV-M. Determination of the median lethal concentration (LC(50)) indicated that CpGV-I12 is nearly as efficient in resistant CpR as CpGV-M in a susceptible CM strain (CpS). Beyond, CpGV-I12 caused superior mortality in CpS. Infection experiments showed that the resistance breaking effect can be observed in all instars of CpR. CpGV-I12 is a promising alternative control agent of CM in orchards where conventional CpGV products fail. In addition, we demonstrate in bioassays with recombinant expressed Cry1Ab that cross-resistance to CpGV and Bacillus thuringiensis products is not likely.

Fluorescent poliovirus for flow cytometric cell surface binding studies.

Specific cell-surface binding is the essential first step for cellular invasion by viruses. To understand this process, various methods to evaluate binding properties of viruses to cells have been developed. However, many rely on radioactive labeling or indirect immunofluorescence. The development of a novel fluorescence binding assay for poliovirus is described. Poliovirus (type 1 Mahoney or Sabin) was labeled directly with fluorescein using a commercially available fluoresceination kit. Fluorescently labeled poliovirus was bound to its specific receptor on Hela or U937 cells and detected by flow cytometric analysis. Specific binding and infectivity was retained, although reduced, depending on the extent of fluoresceination. Therefore, depending on the users' requirements, the extent of fluoresceination must be titrated carefully to achieve maximal fluorescence and minimal functional destruction. It is likely that this method may be useful with other viruses.

Low-density lipoprotein binding affinity of arterial wall proteoglycans: characteristics of a chondroitin sulfate proteoglycan subfraction.

The characteristics of an arterial wall chondroitin sulfate proteoglycan (CS-PG) subfraction that binds avidly to low-density lipoproteins (LDL) was studied. A large CS-PG was extracted from bovine aorta intima-media under dissociative conditions, purified by density-gradient centrifugation and gel filtration chromatography, and further subfractionated by affinity chromatography on LDL-agarose. A proteoglycan subfraction, representing 25% of the CS-PG, showed an elution profile (with dissociation from LDL-agarose occurring between 0.5 and 1.0 M NaCl) corresponding to that of heparin, heretofore considered to be the most strongly binding glycosaminoglycan with LDL. The proteoglycan subfraction which migrated as a single band on composite agarose-polyacrylamide gel electrophoresis contained chondroitin 6-sulfate, chondroitin 4-sulfate and dermatan sulfate in a proportion of 70:22:8. The core protein of the proteoglycan had an apparent molecular weight of 245,000, and contained approx. 33 glycosaminoglycan chains with an average molecular weight of 32,000. The CS-PG subfraction, like heparin, formed insoluble complexes in the presence of 30 mM Ca2+. Complexing of LDL with proteoglycan resulted in two classes of interactions with 0.1 and 0.3 proteoglycan monomer bound per LDL particle characterized by an apparent Kd of 4 and 21 nM, respectively. This indicates that multiple LDL particles bind to single proteoglycan monomers even at saturation. In contrast, LDL-heparin interactions showed a major component characterized by an apparent Kd of 151 nM and a Bmax of 9 heparin molecules per LDL particle. The occurrence of a potent LDL-binding proteoglycan subfraction within the family of arterial CS-PG may be of importance in terms of lipid accumulation in atherogenesis.

Interaction of a high-affinity heparin subfraction with low-density lipoprotein stimulates cholesteryl ester accumulation in mouse macrophages.

A high-affinity heparin subfraction accounting for 8% of whole heparin from bovine lung was isolated by low-density lipoprotein (LDL)-affinity chromatography. When compared to whole heparin, the high-affinity subfraction was relatively higher in molecular weight (11,000 vs. 17,000) and contained more iduronyl sulfate as hexuronic acid (76% vs. 86%), N-sulfate ester (0.75 vs. 0.96 mol/mol hexosamine), and O-sulfate ester (1.51 vs. 1.68 mol/mol hexosamine). Although both heparin preparations formed insoluble complexes with LDL quantitatively in the presence of 30 mM Ca2+, the concentrations of NaCl required for 50% reduction in maximal insoluble complex formation was markedly higher with high-affinity subfraction (0.55 M vs. 0.04 M). When compared to complex of 125I-LDL and whole heparin (H-125I-LDL), complex of 125I-LDL and high-affinity heparin subfraction (HAH-125I-LDL) produced marked increase in the degradation of lipoproteins by macrophages (7-fold vs. 1.4-fold over native LDL, after 5 h incubation) as well as cellular cholesteryl ester synthesis (16.7-fold vs. 2.2-fold over native LDL, after 18 h incubation) and content (36-fold vs. 2.7-fold over native LDL, after 48 h incubation). After a 5 h incubation, macrophages accumulated 2.3-fold more cell-associated radioactivity from HAH-125I-LDL complex than from [125I]acetyl-LDL. While unlabeled HAH-LDL complex produced a dose-dependent inhibition of the degradation of labeled complex, native unlabeled LDL did not elicit any effect even at a 20-fold excess concentration. Unlabeled particulate LDL aggregate competed for 33% of degradation of labeled complex; however, cytochalasin D, known inhibitor of phagocytosis, did not effectively inhibit the degradation of labeled complex. Unlabeled acetyl-LDL produced a partial (33%) inhibition of the degradation of labeled complex. These results indicate that (1) the interaction of high-affinity heparin subfraction with LDL leads to scavenger receptor mediated endocytosis of the lipoprotein, and stimulation of cholesteryl ester synthesis and accumulation in the macrophages; and (2) with respect to macrophage recognition and uptake, HAH-LDL complex was similar but not identical to acetyl-LDL. These observations may have implications for atherogenesis, because both mast cells and endothelial cells can synthesize heparin in the arterial wall.

Composition of proteoglycans synthesized by rabbit aortic explants in culture and the effect of experimental atherosclerosis.

The synthesis of proteoglycans by aorta explants from rabbits with diet-induced atherosclerosis and controls was studied by 35S-incorporation. Proteoglycans were isolated under dissociative conditions from incubation medium and from arterial explants. Additionally, the tissue proteoglycans that were not extracted by 4 M guanidine-HCl were solubilized by digestion of the tissue by elastase in the presence of proteinase inhibitors. The residual tissue was hydrolyzed by papain and glycosaminoglycans were isolated. The atherosclerotic aorta tissue incorporated twice the amount of 35S into proteoglycans than observed for controls; in both groups about 70% of the label incorporated into the tissue was noted in the proteoglycans extracted by guanidine-HC;, while about 30% of the total 35S-labeled proteoglycans synthesized by the explants were found in the media. Atherosclerotic tissue incorporated 35S predominantly into chondroitin sulfate proteoglycans when compared to control tissue. The chondroitinase ABC-digestable proteoglycans that were extracted by guanidine-HCl from atherosclerotic tissues were of larger molecular size than those from control tissue, but the core proteins from these preparations were similar. The heparan sulfate proteoglycan that was obtained by dissociative extraction from atherosclerotic tissue had greater amounts of N-acetyl and lesser amounts of N-sulfate ester groups than the preparation from control tissue. Digestion of the tissue by elastase yielded heparan sulfate proteoglycan as the major constituent in both groups, although atherosclerotic tissue contained relatively small amounts of this proteoglycan. The residual tissue from both groups contained chondroitin sulfate and heparan sulfate as the major glycosaminoglycans with the latter showing a decrease with atherosclerosis. Atherosclerotic tissue secreted into the medium about two-fold more 35S-labeled proteoglycans with larger molecular size than control tissue; proteoglycans of the heparan sulfate and chondroitin sulfate types were the major constituents in the culture medium of both tissues. Thus, proteoglycans undergo both quantitative and qualitative changes in atherosclerosis, reflecting the enhanced smooth muscle cell activity. These changes are potentially important in modulating lipoprotein binding and hemostatic properties, as well as fibrillogenesis of the arterial wall.

Physical association between CD155 and CD44 in human monocytes.

Regulation of CD44-mediated binding to hyaluronan is critical in normal and diseased immune cell function. In earlier work by others (Shepley and Racaniello, J. Virol., 68, 1301 1309), anti-CD44 mAb blocked poliovirus binding to CD155 (the poliovirus receptor) in HeLa cells, suggesting that CD155 and CD44 may be physically associated. Here, we present evidence that CD155 and CD44 are physically associated in human monocytes. In co-modulation experiments in U937 monocytic cells, CD155 and CD44 reciprocally co-modulated. In primary human monocytes, CD 155 syn-capped with CD44. In immunofluorescence flow cytometric experiments, anti CD44 mAb inhibited up to 94% of binding by anti-CD155 mAb which blocks poliovirus binding to CD155. This inhibition was specific for CD155. Culturing monocytes increased the extent of inhibition. In addition, mAb against PRR2, a novel molecule that is related to CD 155, was inhibited by anti-CD44 in a dose-dependent manner, but not by anti-CD14. These data support the interpretation that CD155 (and related proteins) are physically associated with CD44 on monocyte cell surfaces. Although the current study does not address functional significance, we speculate that this interaction may have a role in regulating monocyte CD44 ligand binding which may be critical in pathological processes such as tumor metastasis and arthritis.

Low density lipoprotein binding affinity of arterial wall isomeric chondroitin sulfate proteoglycans.

Although the selective interaction of low density lipoproteins (LDL) with arterial proteoglycans is known, information is lacking on LDL-binding affinity of different subspecies occurring within a proteoglycan family. Isomeric chondroitin sulfate proteoglycan preparations sedimenting at densities of 1.54 g/ml (D1), 1.50 g/ml (D2) and 1.46 g/ml (D3) were isolated from bovine aorta intima-media under dissociative conditions and subjected to equilibrium binding to LDL-agarose gel. D1, D2 and D3 contained 36%, 37% and 11% dermatan sulfate, respectively. Sulfate to hexosamine ratio was low (0.73) in D1 when compared to D2 and D3 (0.94 and 1.04). Of the total proteoglycans contained in D1, D2 and D3, 41%, 52% and 66% interacted with LDL, respectively. LDL-bound proteoglycans dissociated over a wide range of ionic strengths (0.15-1.0); in comparison, LDL-bound heparin dissociated within a narrow range (0.5-0.75). Unlike other preparations, 30% of bound D3 dissociated at an ionic strength of 1.0. In D1 and D2 the proportion of dermatan sulfate increased in proteoglycan fractions that were bound firmly to LDL, whereas a high affinity fraction in D3 contained no dermatan sulfate. Thus, isomeric chondroitin sulfate proteoglycans display considerable divergence with respect to LDL binding. This may depend not only on the degree of sulfation but on other characteristics of the chondroitin sulfate isomers as well.

The role of the aural head shake reflex in serotonin-mediated head shaking behavior.

The head shake reflex is a rapid rhythmic shaking of the head in a radial motion and is a prominent part of the behavior of most mammalian species. The administration of agonists at 5-hydroxytryptamine (5-HT) receptors to rats increases apparently-spontaneous head shaking behavior. The present study examined the relationship between the head shake reflex, elicited by stimulation of the aural ampullae with Tween 80, with a similar-appearing behavior, the head shake response caused by the administration of 5-HT agonists to rats. Head shaking was attenuated by the subcutaneous infiltration of the local anesthetic procaine into the posterior border of the external auditory meatus. However, the local anesthetic did not alter head shake behavior produced by administering either the 5-HT agonist quipazine or the 5-HT precursor 5-hydroxy-L-tryptophan (L-5-HTP). The magnitude of the head shake reflex was also diminished after habituation of the reflex by repeatedly applying Tween 80 to the ampullae, yet this treatment had no effect on the head shaking behavior caused by quipazine. In a complementary manner, pretreatment with the 5-HT2 receptor antagonist ketanserin potently blocked shaking behavior caused by quipazine without significantly altering the head shake reflex. Chronic administration of the atypical antidepressant drug iprindole to rats for 7 days reduced quipazine-induced shaking behavior without affecting the head shake reflex. In contrast, chronic administration of the monoamine oxidase inhibitor phenelzine to rats for 7 days reduced head shaking behavior caused by either stimulus, indicating that an attenuation of motor reflex activity could play a role in the reduced response to quipazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of poliovirus receptors in the spread of the infection.

Although the poliovirus receptor (PVR) has been cloned, lack of knowledge of its precise tissue distribution makes assessment of its role in mediating poliomyelitis difficult. Our recent work demonstrated that PVR is expressed on human monocytes and that primary human blood cells can support PV replication. In the current work, we demonstrate that CD14-positive cells (monocytes) support PV replication but that only a minority (< 10%) of the cells become infected. In other preliminary studies, immunocytochemical analyses of human brain tissue demonstrated the presence of PVR in the olfactory bulb, a tissue thought to not support PV replication. Thus, it appears that some apparently "ectopic" sites of PVR expression may in fact be sites for PV replication, whereas other sites may indeed be restricted. The ability of monocytes to replicate PV may pertain to some unexplained phenomena in PV pathogenesis, such as the specific cell type carrying out the initial round of replication in the gut, sites of extraneural replication and transport of the virus into the CNS. Preliminary studies with monocytes from post-polio syndrome patients showed no difference in the levels of PVR relative to control monocytes. In other preliminary work, PVR was shown to be phosphorylated and its expression on monocytes increased by treatment with gamma-interferon. The normal function of PVR is likely to be involved in monocyte function during immune activation.

The expression of angiogenin in tissue samples of different brain tumours and cultured glioma cells.

BACKGROUND: As a potential angiogenetic factor the 14.1 kDa polypeptide angiogenin induces neovascularisation. MATERIALS AND METHODS: We investigated the angiogenin expression by immunoblotting and an ELISA in 60 tissue specimens (40 gliomas, 20 other intracranial tumours), in 22 glioma cell cultures and in 4 supernantants of cultivated glioblastoma cells. RESULTS: We could show that angiogenin is detectable in different kinds of intracranial tumours with the highest amount in meningiomas and the lowest amount in low grade astrocytomas. In tissue specimens, a significantly higher angiogenin expression was measured in meningiomas compared to gliomas and metastases. Angiogenin could be detected in primary cultivated glioma cells, but not in the permanent cell lines. There was a significant correlation to the malignancy within the gliomas with an increase of angiogenin concentration according to the higher grade of malignancy. CONCLUSIONS: Our data suggest that angiogenin may contribute to the malignant transformation of gliomas and could perhaps advise that the physiological role of angiogenin is not restricted exclusively to angiogenesis. Based on these findings the clinical importance of angiogenin for therapeutic decisions in malignant brain tumours remains unclear and further analyses on m-RNA-levels are required.

First tests of a liquid ionization chamber to monitor intensity modulated radiation beams.

First measurements with a prototype ionization chamber are described to be applied in online monitoring of modulated fields in radiation therapy. The liquids isooctane, isononane (TMP) and tetramethylsilane (TMS) are used in a high purity grade in order to realize high current signals for electronic read-out in parallel at frequencies exceeding 10 Hz. Signals of more than a factor 4 with respect to isooctane, analysis grade, are obtained. With an electrode structure of 400 pads, a uniformity in efficiency within 1.2% has been measured. The penumbra of a multileaf collimator could be resolved. Theoretical examination verifies that the free electrons in the liquids cause higher signals when the measured currents are compared with expectation for ion transport only.

The innervation of the great saphenous vein: an immunohistochemical study with special regard to regulatory peptides.

The human great saphenous vein is often used in by-pass surgery. In spite of its importance little is known about the neuronal regulation and innervation of this vessel. On the other hand, therapeutic phlebectomy of the saphenous vein provides a good basis for investigations on the nervous supply of human veins. In former studies the human great saphenous vein has been proved to be a richly innervated portion of the low pressure vascular system. We studied the innervation of the proximal femoral saphenous vein by immunohistochemical methods and with special regard to regulatory neuropeptides. A peptidergic innervation mainly localized along the vasa vasorum and associated with immunoreactivity of substance P and CGRP was found which yields evidence for a mechanosensory innervation of this vascular segment.

CD34+ hematopoietic stem cells support entry and replication of poliovirus: a potential new gene introduction route.

Pluripotent hematopoietic stem cells (HSC) are critical in sustaining and constantly renewing the blood and immune system. The ability to alter biological characteristics of HSC by introducing and expressing genes would have enormous therapeutic possibilities. Previous unpublished work suggested that human HSC co-express CD34 (cluster of differentiation 34; an HSC marker) and CD155 (poliovirus receptor; also called Necl-5/Tage4/PVR/CD155). In the present study, we demonstrate the co-expression of CD34 and CD155 in primary human HSC. In addition, we demonstrate that poliovirus infects and replicates in human hematopoietic progenitor cell lines. Finally, we show that poliovirus replicates in CD34+ enriched primary HSC. CD34+ enriched HSC co-express CD155 and support poliovirus replication. These data may help further understanding of poliovirus spread in vivo and also demonstrate that human HSC may be amenable for gene therapy via poliovirus-capsid-based vectors. They may also help elucidate the normal function of Necl-5/Tage4/PVR/CD155.