PURPOSE:The objective of the present study was to investigate whether the sonographic visualization of lateralization of the femoral head is comparable to magnetic resonance imaging (MRI) and would therefore be able to contribute to the diagnosis of containment in patients with Perthes disease.MATERIALS AND METHODS:46 patients with unilateral Perthes disease (age: 5.9 +/- 2.3 years) of Catterall group III/IV were evaluated at first presentation by means of ultrasound (US) and MRI of both hip joints to evaluate the morphology of the acetabular lip (LA) and the epiphysis (EP). The diagnosis of containment was performed in MRI as well as in US by the protrusion and deformity of the epiphysis of the femoral head with cranialization of the labrum. The evaluation of the sonographic and MRI findings was carried out independently by three observers (high experience: 1, 2, low experience: 3). Statistical analysis was performed using Cohen's non-weighted kappa kappa (kappa > 0.75 very high level of correlation). The study was conducted in accordance with the recommendations of the local ethics committee that approved our study.RESULTS:There was a high to very high agreement of the morphology of the LA and EP between observers 1 and 2 (MRI: LA: kappa = 0.87; EP: kappa = 0.90; US: LA kappa = 1.0; EP: kappa = 0.57). The comparison of observers 1 and 2 with observer 3 showed only a poor to acceptable level of agreement. US agreed well with MRI in the evaluation of the containment of the femoral head (1: kappa = 0.79; 2: kappa = 0.70, 3: kappa = 0.72).CONCLUSION:The results of our study suggest that US is a reliable examination method for monitoring the containment of the femoral head in Perthes disease. The evaluation of both methods depends on the experience of the observer.

Although Nystatin has been used since 1950s as a non-absorbable antifungal agent, there is still no reliable in-vivo data available stating a dose-effect relationship of Nystatin-suspension in the treatment of oropharyngeal infection with Candida albicans. Here, we studied the efficacy of a commercially available topical Nystatin suspension in a new ex-vivo model of candidiasis using porcine oral mucosa. After 48 and 96 h of C. albicans infection, 230 IU Nystatin (standard dosage), 100 IU and 20 IU proved to be equally efficacious. Multiple applications of Nystatin were not superior compared with single application. In dosages of 10 and 0.1 IU the activity of Nystatin suspension against C. albicans was no longer confirmed. In an agar diffusion model, the minimal biocidal concentration of Nystatin proved to be 0.25 IU. Our results suggest that the proposed porcine ex-vivo model is much closer to the in-vivo situation compared with other established in-vitro models of the treatment of muco-cutaneous candidiasis and may provide a substitute for animal models in the investigation of antifungal agents. Additionally, it seems to be a valuable tool for further investigations of the pathogenesis of C. albicans infections.

P-641 Introduction: For the successful application of (probabilistic) exposure modelling, both sufficient data of good quality and guidance on their use are necessary. A German report on exposure factors dating from 1995 was partially made obsolete by recent studies and by requirements of probabilistic exposure modelling. The Xprob project aimed to evaluate recent data and methods of probabilistic exposure assessment, to derive distributions for exposure factors, and to provide guidelines on good practice of probabilistic exposure modelling. Methods: Comprehensive data and literature searches with focus on German sources were carried out, taking the 1995 report as a basis. These sources were analysed in a standardised way. A methodology for deriving distributions needed for probabilistic modelling was developed, based on a US EPA approach. This methodology was then applied to analyse the data sources. In addition, literature reviews were carried out to assess the quality of data sources and to fill data gaps. A database was developed and implemented for structured documentation and retrieval of the information gathered. Results: Based on more than 50 data and literature sources, recommendations concerning derived distributions of human exposure factors were made. They can also be used for point estimates. In the database RefXP developed by the project, the distributions and characteristics of the individual exposure factors are provided, structured by thematic areas. Information is given on data source, exposure factor, empirical and derived distribution, each stratified by age and gender. For some exposure factors (e.g. inhalation, soil ingestion), only data from literature were available. Various data gaps were identified. Discussion and Conclusions: The provision of distributions as well as point estimates for exposure factors in a uniformly structured database offers clear advantages. The distributions fit the empirical data. For filling remaining data gaps, the developed methodology should be used to evaluate recent studies hitherto inaccessible, as well as future studies. Derived principles of good practice will facilitate the application of probabilistic exposure modelling. Distribution based exposure reference values can contribute to a harmonisation of the assessment of environmental health risk assessment. Implementation into administrative policy, however, calls for additional support and practice-oriented developments. This project was funded by the German Federal Environmental Agency (UBA) under No. FKZ 20261218/02.

Background and objective: To compare the anaesthetic characteristics in terms of onset and offset times of the sensory and motor blocks of prilocaine 1% and ropivacaine 0.75% alone and in different combinations when used for brachial plexus anaesthesia in axillary perivascular blocks. Methods: After informed consent 96 ASA I–III patients undergoing forearm or hand surgery participated in this prospective, randomized, double‐blind study. Patients received either prilocaine 1% 40 mL (G1), prilocaine 1% 30 mL and ropivacaine 0.75% 10 mL (G2), prilocaine 1% 20 mL and ropivacaine 0.75% 20 mL (G3) or ropivacaine 0.75% 40 mL (G4) for axillary perivascular brachial plexus anaesthesia. Onset and duration of sensory and motor blocks in the distribution of the musculocutaneous, radial, median and ulnar nerves were assessed. Results: The onset time of the sensory and motor blocks of the whole brachial plexus differed only between patients in G4 with ropivacaine 0.75% 40 mL demonstrating a later motor onset in comparison to all other groups and a later sensory onset in comparison to G1 and G2 (P < 0.01). The addition of ropivacaine resulted in longer offset times of the sensory and motor blocks. The median offset time of the motor block was 179.5 min in G1, 262 min in G2, 389.5 min in G3 and 745 min in G4 (P < 0.01). The median offset time of the sensory block was 163.5 min in G1, 277 min in G2, 383.5 min in G3 and 784 min in G4 (P < 0.01). There was no difference in onset and offset times between sensory and motor blocks within the groups. Conclusions: For axillary perivascular brachial plexus block prilocaine 1% alone and in combination with ropivacaine 0.75% was similar in terms of onset of sensory and motor blocks but different in duration of sensory and motor blocks without a differential sensory and motor offset.

P-730 Abstract: In 1995 the German Committee for Environmental Hygiene (AUH) published the first German Exposure Factors Handbook (Standards zur Expositionsabschätzung). This handbook compiles many variables influencing the uptake such as inhalation rates, food consumption or anthropometric data. Ten years later the German Federal Environmental Agency (UBA) funded the Xprob-project to evaluate and update these information. One objective was to generate input distributions for use in probabilistic exposure modelling. The project started with the definition of a uniform report format for probabilistic exposure factors. The format will provide the user with all information necessary for choosing the desired exposure factor, for computing a deterministic or probabilistic exposure model, for evaluating the uncertainties and discussing model alternatives. All information are provided in a structured electronic database, which could be extended by the users and/or the funding institution. This form offers clear advantages compared to the actual state where data are presented isolated and in unequal quality. In a second step criteria for the evaluation of empirical data were discussed. The project chose a minimal set of requirements, which is needed for the fit of a distribution to the data. A generalized F-distribution with point mass at zero was estimated using the maximum likelihood principle. For practical reasons a subdistribution with two parameters and point mass at zero was determined by minimising the likelihood ratio. To incorporate additional information on strata, especially on sex and on age, a method was developed, which divides the population in homogeneous subgroups. The F-statistic was used here as criteria for optimisation. The determination of distributions goes on unsupervised and in the same manner for all (continuous, positive) exposure factors. The procedure is transparent; in particular, the achieved goodness of fit is described. The program code will be freely available at the end of the project. The results comply with the proposed report format and are harmonized in the sense that they share the same assumptions. The rationale behind the procedure will be compared with alternative methods. We will discuss the use of the report format and the database, exemplified by some exposure factors. An outlook to further enhancements is given, like fitting of censored and multidimensional data. Approaches for two-dimensional exposure models, which also take the uncertainty of the fit into consideration, will be discussed too. Finally we combine the exposure assessment with a probabilistic effect assessment and discuss the benefit for a transparent and rational regulation.

Hintergrund: Die Berechnung der präventierbaren Anteile in populationsbasierten Risikoschätzungen basiert auf hinreichendem Wissen über die relativen Risiken und die Prävalenz der Risikofaktoren. In der Regel werden diese als zeitstabil sowie als konstant über das Alter und das Geschlecht angenommen. Diese Annahmen sind insbesondere für zeitlich rückreichende Expositionen nur grobe Näherungen, für kumulative oder für prospektiv vermeidbare Expositionen sind sie unzureichend. Ziel: In einem Simulationsansatz wird die erwartete Inzidenz von kritischen Ereignissen am Beispiel des Lungenkarzinoms und der Herz-Kreislauf-Mortalität für aktuelle Raucher (mit Fortschreibung der Rauchgewohnheiten) im Kontrast zu „jetzt aktuell aufhörenden Rauchern“ berechnet. Methoden: Die Erwartungswerte werden über ein zeit-, alters- und geschlechtsabhängiges Modell (Markoff-Modell mit abhängigen Transitionswahrscheinlichkeiten) berechnet. Eingangsdaten sind auf Surveydaten basierende Angaben zur Expositionsbiographie für die nicht exponierte und für die prognostisch weiter exponierte Gruppe; die „prognostisch nicht mehr Exponierten“ wurden als unabhängige Größe (Präventionsgruppe) in das Modell aufgenommen. Die anzunehmenden altersabhängigen relativen Risiken (Risikofortschreibungen) mit und ohne Prävention basieren auf den Analysen der IARC. Ergebnisse: Die relative Änderung der Inzidenzerwartung ist über die Präventionsannahmen stark alters- und geschlechtsabhängig. Schlussfolgerungen: Das Modell zeigt, dass die Vermeidung von Risikofaktoren noch in der älteren Bevölkerung erhebliche, z.T. überproportionale Gewinne in der Lebenserwartung gegenüber ihrer Erwartung bei Risikofortschreibung erzielen kann.

Hintergrund: Die Bedeutung der Expositionsabschätzung im Rahmen der populationsbezogenen Risikoabschätzung wird zunehmend national [1] und international [2, 6] anerkannt. Für die Bildung von Standards zur Expositionsabschätzung ist es notwendig, Klarheit über grundlegende methodische Fragen und über die Qualität der Datengrundlagen zu gewinnen. Zur Wahrung des Grundrechtes auf körperliche Unversehrtheit ist es dabei notwendig, neben einem durchschnittlichen Fall auch ungünstige Umstände zu betrachten, also Variation in den Expositionsbedingungen angemessen zu berücksichtigen. Der Ausschuss für Umwelthygiene (AUH) hat für die Bundesrepublik 1995 Vorschläge für Standards [3] entwickelt. Ziel: Nach Evaluation der Standards wurde deutlich, dass erhebliche Datenlücken bestehen und eine Aktualisierung geboten ist. Innerhalb des Projektes Xprob (Kooperationsprojekt Universitäten Bielefeld, Bremen und Hamburg sowie Landesgesundheitsamt Niedersachsen /UBA-gefördertes Projekt) wird diese Aufgabe bearbeitet. Methoden: Dokumentation bestehender Datenquellen (Surveys) als Basis der Ableitung von empirisch gesicherten Standards, Definition von Qualitätsanforderungen an Surveydaten (aus der Sicht der populationsbezogenen Expositionsabschätzung), Adaptation und Programmierung von US-EPA-Methoden [4] zur deskriptiven Beschreibung und Dokumentation von Verteilungen relevanter Parameter, Entwicklung einer interaktiv nutzbaren Datenbank für die Dokumentation und den Zugriff auf existierende und neu abgeleitete Expositionsstandards, Publikation eines Leitfadens zur Durchführung von populationsbezogenen Expositions- und Risikoabschätzungen. Ergebnisse: Die Methoden wurden auf nationale Surveydaten und Sekundärdaten angewandt und einer externen Qualitätssicherung (UBA-Symposium 28.-29.1.2004) unterzogen. Diskussion: Der aktuelle Stand der Ergebnisse und die Verzahnung zu weiteren internationalen Projekten werden vorgestellt. Literatur: 1. APUG: Aktionsprogramm Umwelt und Gesundheit, http://www.apug.de .2. EC: First Report on the harmonisation of risk assessment procedures. Report SSC Working Group, EC 26–27 October 2000. 3. AUH (1995): Standards zur Expositionsabschätzung. BAGS Hamburg (Hrsg.), 1995. 4. EPA U.S.(2000): Options for Development of Parametric Probability Distributions for Exposure Factors.: EPA/600/R-00/058, Washington 5. Expofacts: Tenhola V. et al.: European Exposure Factors Handbook, www.ktl.fi/expofacts. 6.WHO (1999) Principles for the Assessment of Risks to Human Health from Exposure to Chemicals. IPCS EHC 210, WHO, Geneva.