[Patient representatives at the federal state level in Germany - results of a quantitative survey regarding the educational needs of patient representatives]. / Patientenvertretung auf der Ebene der Bundesländer - Ergebnisse einer quantitativen Befragung zu den Bildungsbedürfnissen von Patientenvertretern und Patientenvertreterinnen.

OBJECTIVES: During the last decades patient and public involvement has gained more and more political approval. An important milestone regarding collective patient interests was the Statutory Health Insurance Modernisation Act in 2004 (§ 140 f SGB V). No systematic research has been conducted regarding the situation of patient representatives at the federal state level as yet. The aim of the following study is to close this gap, focusing on educational needs of patient representatives. METHODS: After screening the literature we identified and discussed relevant aspects of patient participation in a focus group of 7 patient representatives. Based on these findings a standardised questionnaire was developed in cooperation with scientists and patient representatives. We sent the written questionnaire to 504 patient representatives at the federal state level. The survey was targeted at patient representatives who currently participate or have in the past participated in a committee at federal state level according to § 140 f SGB V. RESULTS: A total of 184 completed questionnaires was returned for an overall response rate of 36.5%. Most respondents felt poorly prepared for their role and regard a compulsory preparation course as necessary. Patient representatives want to be an active part in the decision-making process of the committee meetings. They report educational needs on different topics and they are willing to close these gaps. For the future, patient representatives expect increasing significance of collective participation. CONCLUSION: The results can be used to develop educational programmes for patient representatives in order to qualify them for the best possible performance of their tasks. Furthermore the results can provide a scientific basis for political discussions and for reasoning capacity building of patient representatives.

Regulation of host immune responses by modification of Salmonella virulence genes.

Modifying bacterial virulence genes to probe the nature of host immunity is mostly unexplored. Here we investigate whether host immune responses can be regulated by modification of bacterial virulence genes. In mice, attenuated Salmonella mutant strains with clinical relevance elicited differential host immune responses. Oral administration of a mutant strain with a PhoP-null phenotype promoted potent innate immune responses of macrophages that were sufficient for host defense. In contrast, administration of an Aro- mutant strain elicited stronger specific antibody and T-helper (Th)-cell responses, wherein Th1-type cells were required for clearance. Thus, genetic manipulation of bacteria may be used to broadly alter immune mechanisms that regulate attenuation within the host and to tailor host immunity to specific bacterial pathogens.

Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota.

BACKGROUND AND AIMS: The intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated. METHODS: Bacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria. RESULTS: IAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium). CONCLUSIONS: IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.

Innervation of periosteum and bone by sympathetic vasoactive intestinal peptide-containing nerve fibers.

Neural control of bone metabolism and growth has been suggested, although the identity of participating neurons and neurotransmitters effecting this control has not been established. Immunohistochemical studies demonstrated a system of vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers that innervate periosteum and bone in several mammalian species. Thoracic sympathetic chain ganglionectomy resulted in an ipsilateral loss of VIP-immunoreactive fibers in the periosteum of ribs, whereas dorsal root ganglionectomy had no effect. Injection of fast blue into rib periosteum labeled a population of VIP-immunoreactive sympathetic postganglionic neurons. Thus, postganglionic sympathetic neurons may provide an important means by which VIP regulates bone mineralization.

COMPARISON OF DIFFERENT PADC MATERIALS AND ETCHING CONDITIONS FOR FAST NEUTRON DOSIMETRY.

Etched-track polyallyl diglycol carbonate (PADC) dosemeters have been in use at the Paul Scherrer Institute since 1998 in neutron dosimetry for individual monitoring. In the last years, the availability of PADC materials from different manufacturers has grown, and different etching conditions were proposed, with the intention to improve the quality and overall performance of PADC in individual neutron monitoring. The goal of the present study was to compare the performance of different PADC materials and to investigate the influence of different etching conditions on sensitivity to fast neutrons and lower detection limit. The comparison covers six different PADC materials and eight different etching conditions.

Does the relative density of periarticular bone influence the failure pattern of intra-articular fractures?

INTRODUCTION: The architecture of joints almost certainly influences the nature of intra-articular fractures, and the concavity is much more likely to fail than the associated convexity. However, local differences in periarticular bone density potentially also plays a critical role. The purpose of this study was to investigate if there was any difference in periarticular bone density in intra-articular fractures between the two opposing joint surfaces, comparing the convexity to the concavity. MATERIALS AND METHODS: We retrospectively identified a series of 1003 intra-articular fractures of the hip, knee, and ankle; 129 of these patients had previously undergone CT scanning during their routine clinical assessment. Periarticular bone density was assessed using Hounsfield Units (HU) as a measure of the composite density of the adjacent bone. Bone density was compared between the opposite sides of each joint, to determine if a relationship exists between local bone density and the risk of articular surface fracture. RESULTS: There was a statistically significant difference in density between the two opposing surfaces, with the convexity 19% more dense than the concavity (p=0.0001). The knee exhibited the largest difference (55%), followed by the hip (18%); in the ankle, an inverse relationship was observed, and the concave surface was paradoxically denser (5%). There was no significant difference between those cases where the concavity failed in isolation compared to those where the convexity also failed (p=0.28). CONCLUSION: When the results were pooled for all three joints, there was a statistically significant higher local bone density demonstrated on the convex side of an intra-articular fracture. However, while this relationship was clearly exhibited in the knee, this was less evident in the other two joints; in the ankle the reverse was true, and the local bone adjacent to the concavity was found to have greater density. This suggests local bone density plays only a minor role in determining the nature of intra-articular fractures.

[Osteoarthritis from long-distance running?]. / Osteoarthrose durch Langstreckenlaufen?

Long distance running has become a fashionable recreational activity. This study investigated the effects of external impact loading on bone and cartilage introduced by performing a marathon race. Seven beginners were compared to six experienced recreational long distance runners and two professional athletes. All participants underwent magnetic resonance imaging of the hip and knee before and after a marathon run. Coronal T1 weighted and STIR sequences were used. The pre MRI served as a baseline investigation and monitored the training effect. All athletes demonstrated normal findings in the pre run scan. All but one athlete in the beginner group demonstrated joint effusions after the race. The experienced and professional runners failed to demonstrate pathology in the post run scans. Recreational and professional long distance runners tolerate high impact forces well. Beginners demonstrate significant changes on the post run scans. Whether those findings are a result of inadequate training (miles and duration) warrant further studies. We conclude that adequate endurance training results in adaptation mechanisms that allow the athlete to compensate for the stresses introduced by long distance running and do not predispose to the onset of osteoarthritis. Significant malalignment of the lower extremity may cause increased focal loading of joint and cartilage.

Does joint architecture influence the nature of intra-articular fractures?

INTRODUCTION: The architecture of joints has potentially the greatest influence on the nature of intra-articular fractures. We analysed a large number of intra-articular fractures with two aims: (1) to determine if the pattern of injuries observed supports our conjecture that the local skeletal architecture is an important factor and (2) to investigate whether associated dislocations further affect the fracture pattern. METHODS: A retrospective study of intra-articular fractures over a 3.5-year period; 1003 joints met inclusion criteria and were analysed. Three independent investigators determined if fractures affected the convex dome, the concave socket, or if both joint surfaces were involved. Further review determined if a joint dislocation occurred with the initial injury. Statistical analysis was performed using a one-way frequency table, and the χ(2) test was used to compare the frequencies of concave and convex surface fractures. The odds ratios (ORs) were calculated to establish the association between the frequencies of concave and convex surface fractures, as well as between dislocation and either fracture surface involvement. RESULTS: Of the 1003 fractures analysed, 956 (95.3%) involved only the concavity of the joint; in 21 fractures (2.1%) both joint surfaces were involved; and in 26 fractures (2.6%) only the convexity was involved (χ(2)=1654.9, df=2, p<0.0001). As expected, the concavity was 20.8 times more likely to fail than the convexity (11.2-36.6, 95% CI). However, the risk of fracturing the convex surface was 18.6 times higher (9.8-35.2, 95% CI) in association with a simultaneous joint dislocation, compared to those cases without a joint dislocation. CONCLUSIONS: These results very strongly support the study hypotheses: the skeletal architecture of joints clearly plays a highly significant role in determining the nature of intra-articular fractures. Intra-articular fractures involving the convexity are much more likely to be associated with a concurrent joint dislocation.

Reference instruments based on spectrometric measurement with Lucas Cells.

The Bundesamt für Strahlenschutz (Berlin, Germany) and the Paul Scherrer Institute (Villigen, Switzerland) both operate accredited calibration laboratories for radon gas activity concentration. Both the institutions use Lucas Cells as detector in their reference instrumentation due to the low dependence of this detector type on variations in environmental conditions. As a further measure to improve the quality of the reference activity concentration, a spectrometric method of data evaluation has been applied. The electric pulses from the photomultiplier tube coupled to the Lucas Cells are subjected to a pulse height analysis. The stored pulse height spectra are analysed retrospectively to compensate for fluctuations in the electric parameters of the instrumentation during a measurement. The reference instrumentation of both the laboratories is described with the respective spectrum evaluation procedures. The methods of obtaining traceability to the primary calibration laboratories of Germany and Switzerland and data of performance tests are presented.

Using gaseous emissions of a proton accelerator facility as tracer for small-scale atmospheric dispersion.

The gaseous effluents of the proton accelerator facility located in the Western part of the Paul Scherrer Institute, Aargau, Switzerland, contain a mixture of positron emitters (50 % (15)O, 20 % (13)N and 30 % (11)C). For the experimental verification of a future upgrade of the dispersion model in the complex topography of the Aare valley, a measuring campaign using three continuous gamma-spectrometric measuring stations was launched in 2011. The concept of a modified man-made-gross-count (MMGC) ratio yields a clear signal associated with the positron emitters while minimising the influence of radon progeny rain-out events. A dependence of the measured MMGC ratios on the emitted activity and wind direction could be demonstrated using frequency distributions of the modified MMGC ratio measured in 2012 and 2013. A significant fraction of high MMGC-ratio values was found associated with dispersion directions (based on measurements of the wind direction in 70 m above ground) not towards or even against the direction between stack and measuring station.

Functional receptors for vasoactive intestinal peptide on human osteosarcoma cells.

We have previously reported that vasoactive intestinal peptide (VIP) stimulates bone resorption in organ culture via a cAMP-dependent mechanism. Here we describe functional receptors for VIP on a clonal line of human osteosarcoma cells, SaOs-2. SaOs-2 cells respond to VIP with an increase in cAMP. The effect was rapid (2 min) and dose dependent from 0.15-15 nM VIP, with half-maximal stimulation at 1.4 nM. SaOs-2 cells produce prostaglandin E2 (PGE2) and respond to exogenous PGE2 with increases in cAMP approximately one third as great as those induced by VIP. However, the VIP-stimulated increases in cAMP occurred without detectable increases in PGE2 production, and increases in cAMP were unaffected by the cyclooxygenase inhibitor indomethacin. SaOs-2 cells pretreated with VIP for 24 h were significantly less responsive to a second acute challenge with VIP, but retained their ability to respond to PGE2. Similarly, pretreatment with PGE2 induced homologous desensitization to PGE2, but had no effect on the VIP-stimulated increase in cAMP. These patterns of response paralleled those previously described in whole bone in organ culture. Binding studies with [125I]VIP demonstrated specific, saturable, high affinity receptors for VIP on SaOs-2 cells. Scatchard analysis of [125I]VIP binding at 37 C resulted in a curvilinear plot. Analysis based upon the assumption of two independent binding sites gave Kd values of 0.44 and 17 nM for high and low affinity binding sites, respectively. The numbers of high and low affinity sites per cell were determined to be 8,500 and 57,000, respectively. Binding of [125I]VIP was partially inhibited by two related peptides, secretin and PHI-27, but not by PTH, calcitonin or a variety of unrelated peptides. We conclude that the action of VIP on human SaOs-2 cells is similar to that observed in intact mouse calvaria, and that these cells provide a good model for the study of the initial steps of VIP action in bone.

Platelet-derived growth factor stimulates bone resorption via a prostaglandin-mediated mechanism.

Platelet-derived growth factor (PDGF) stimulated up to 15-fold the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvaria in organ culture. The action of PDGF on bone resorption occurred at low concentrations of the protein (ED50 = 10 ng/ml). All concentrations of PDGF which stimulated resorption also enhanced the production of PGE2 by bone; concentrations of PDGF which did not stimulate resorption did not enhance PGE2 production. PDGF-induced formation of PGE2 and bone resorption were inhibited completely by indomethacin (100 ng/ml) and hydrocortisone (1 microgram/ml). Indomethacin did not inhibit the bone resorption-stimulating activity of exogenous PGE2. In the continued presence of a maximum concentration of PDGF (100 ng/ml), an increase in bone resorption, as measured by an increase in medium calcium, was detected at 16 h (P less than 0.01), but not at 12 h; however, an increase in PGE2 production occurred within the first 2 h of treatment. A similar lag period for the onset of bone resorption was seen after the addition of exogenous PGE2 to the culture medium. On the other hand, exposure of bones to PDGF (50 ng/ml) for as brief a period as 5-15 min, followed by washout of PDGF, triggered bone resorption over the subsequent 48 h. PDGF increased cAMP production by bone within 30 min, and this effect of PDGF was blocked completely by indomethacin while the action of exogenous PGE2 on the production of cAMP was not blocked by indomethacin. The action of a low concentration of PDGF (1 ng/ml), which did not stimulate bone resorption alone, was potentiated by the phosphodiesterase inhibitor isobutylmethylxanthine (4 microM). We conclude that low concentrations of PDGF stimulate bone resorption via the enhanced local production of PGE2.

Central nervous system infection with Listeria monocytogenes. 33 years' experience at a general hospital and review of 776 episodes from the literature.

We reviewed 776 previously reported and 44 new cases of CNS listeriosis outside of pregnancy and the neonatal period, and evaluated the epidemiologic, diagnostic, and therapeutic characteristics of this infection. Among patients with Listeria meningitis/meningoencephalitis, hematologic malignancy and kidney transplantation were the leading predisposing factors, but 36% of patients had no underlying diseases recognized. The infection occurred throughout life, with a higher incidence before the age of 3 and after the age of 45-50 years. Fever, altered sensorium, and headache were the most common symptoms, but 42% of patients had no meningeal signs on admission. Compared with patients with acute meningitis due to other bacterial pathogens, patients with Listeria infection had a significantly lower incidence of meningeal signs, and the CSF profile was significantly less likely to have a high WBC count or a high protein concentration. Gram stain of CSF was negative in two-thirds of cases of CNS listeriosis. One-third of patients had focal neurologic findings, and approximately one-fourth developed seizures over their course. Mortality was 26% overall, and was higher among patients with seizures and those older than 65 years of age. Relapse occurred in 7% of episodes. Ampicillin for a minimum of 15-21 days (with an aminoglycoside for at least the first 7-10 days) remains the treatment of choice. Cerebritis/abscess due to L. monocytogenes, without meningeal involvement, is less common but may be diagnosed by blood cultures and CNS imaging, or by stereotactic biopsy. Longer antibiotic therapy (at least 5-6 weeks) is needed in the presence of localized CNS involvement.

[Epidemiology of recreational runners]. / Epidemiologie des Freizeitläufers.

Running has become a very popular sport in Europe. We clinically examined the feet of 92 recreational runners and assessed their knowledge of their own foot anatomy with a questionnaire. Additionally a podogram was performed by an experienced podiatrist. 41 runners trained for more than 5 years, 12 between 3-5, 28 between 1-3 and 11 less than one year. The mean age was 35.4 years. The majority had weekly distances of less than 20 km (n = 43) and 20-40 km (n = 28), 14 40-60 km and only 6 runners were running more than 60 km per week. We could define two groups: one group as the sedentary runner with distances less than 20 km over a minimum period of 3 - 5 years and the competitive runner with distances above 40 per week over at least 3 years. Most of the runners run on tarred or gravel surfaces or a combination of those. The knowledge of the own foot anatomy and biomechanics was poor. Only 50% were correct in identifying their anatomy. 30% of all runners have been given orthotics of which only 50% demonstrated an improvement in symptoms.

[Fatal child neglect in West Germany 1 January 1985 to 2 October 1990. Results of a multicenter study]. / Tödliche Kindesvernachlässigung in der Bundesrepublik Deutschland im Zeitraum 1.1.1985 bis 2.10.1990. Ergebnisse einer multizentrischen Studie.

UNLABELLED: Up to now reliable data were available on cases of lethal child neglect in the area of the Federal Republic of Germany prior to reunification (the former West Germany). In a multicenter study we therefore examined the police and court records for such cases occurring in the period from 1 January 1985 to 2 October 1990 in nearly the entire area of Federal Republic of Germany. RESULTS: The study center received information on 19 cases of lethal child neglect. Extrapolated to all institutes of legal medicine, this corresponds to 20 cases and thus 3.5 cases a year in the whole of West Germany in the period studied. There is to be added a dark-field which cannot be limited more precisely. However, the cases of fatal child neglect might have occurred much more seldom than fatal child abuse caused by use of physical violence. Slightly more than half the victims were younger than 1 year, the oldest one was 7 10/12 years old. Most frequently the children died of starvation and thirst. Mostly the mothers/nursing mothers killed the child alone or together with the victim's father/stepfather. In the majority of the cases there was not a close affection between parents and child. Nearly 30% female/male perpetrators suffered from chronic alcohol abuse. Only 15 (= 56%) of 27 female/male perpetrators were sentenced to imprisonment (period between 7 months on probation and 10 years). Mitigation circumstances existed for nearly half the persons sentenced to imprisonment. It is true that child neglect is a rarer crime, but the experts of legal medicine always have to indicate errors made during the external inspection of the corpse (among others failures to see indications of neglect).

[Fatal child abuse (caused by physical violence) in Germany during 1 January 1985 to 2 October 1990. Results of a multicenter study]. / Tödliche Kindesmisshandlung (durch physische Gewalteinwirkung) in der Bundesrepublik Deutschland im Zeitraum 1.1.1985 bis 2.10.1990. Ergebnisse einer multizentrischen Studie.

UNLABELLED: No reliable data are available on cases of lethal child abuse (by active force) in the area of Federal Republic of Germany prior to reunification (the former West Germany). In a multicenter study we therefore examined the police and court records for such cases occurring in the period 1 January 1985 to 2 October 1990 in nearly the entire area of Federal Republic of Germany. RESULTS: The study center received information on 58 cases of lethal child abuse. Extrapolated to all institutes of legal medicine, this corresponds to 62 cases in all of West Germany in the period studied. An approximately equal number of unreported cases should be added to this figure. Including unreported cases, at least 20 cases of lethal child abuse occurred per year; thus only one in every two cases ever came to light. Almost two thirds of the victims were younger than one year old. At autopsy 59% exhibited signs of repeated abuse at autopsy. By far the most common cause of death was direct impact from a blunt object, usually to the head. Mostly, the male person to whom the victim relates most closely (father, stepfather, partner of the mother) has killed the child. Twenty-one of the 74 persons charged saw the charges against them dropped or were acquitted due to lack of evidence; 51 received sentences ranging from one year probation to life. In the remaining two cases the outcome of the trial was unknown. Signs of abuse were readily apparent at autopsy in almost all cases. The high number of unreported cases underscores the need to educate medical students and practicing physicians to be on the look-out for signs of abuse and argues for an increase in the rate of autopsy.

Neutron dose rate at the SwissFEL injector test facility: first measurements.

At the Paul Scherrer Institute, the new SwissFEL Free Electron Laser facility is currently in the design phase. It is foreseen to accelerate electrons up to a maximum energy of 7 GeV with a pulsed time structure. An injector test facility is operated at a maximum energy of 300 MeV and serves as the principal test and demonstration plant for the SwissFEL project. Secondary radiation is created in unavoidable interactions of the primary beam with beamline components. The resulting ambient dose-equivalent rate due to neutrons was measured along the beamline with different commercially available survey instruments. The present study compares the readings of these neutron detectors (one of them is specifically designed for measurements in pulsed fields). The experiments were carried out in both, a normal and a diagnostic mode of operation of the injector.

A new version of the LUPIN detector: improvements and latest experimental verification.

LUPIN-II is an upgraded version of LUPIN, a novel rem counter first developed in 2010 specifically conceived to work in pulsed neutron fields (PNFs). The new version introduces some modifications that improve the performance of the detector, in particular extending its upper detection limit in PNFs. This paper discusses the characteristics and the performance of the instrument. Measurements have been carried out in radiation fields characterized by very different conditions: the detector has first been exposed in PNFs with intensity up to 5 µSv per burst, where it could keep the H*(10) underestimation below 20% up to 500 nSv per burst. It has then been tested in operational conditions around particle accelerators, where it has shown performances similar to that of ionization chambers. Its proper functioning has also been verified in high energy mixed fields, where the experimental results matched the Monte Carlo predictions. Its neutron/photon discrimination capability has been tested in a steady-state photon field where, via an innovative technique based on a threshold set on the derivative of the current signal, it was capable of rejecting a photon H*(10) rate of about 25 mSv/h, and in a mixed neutron/photon field, where a time-based discrimination method was employed.

A comparison of the response of PADC neutron dosemeters in high-energy neutron fields.

Within the framework of the EURADOS Working Group 11, a comparison of passive neutron dosemeters in high-energy neutron fields was organised in 2011. The aim of the exercise was to evaluate the response of poly-allyl-glycol-carbonate neutron dosemeters from various European dosimetry laboratories to high-energy neutron fields. Irradiations were performed at the iThemba LABS facility in South Africa with neutrons having energies up to 66 and 100 MeV.