Die Spontanheilungsversuche des vorderen Kreuzbands : eine experimentelle Untersuchung

Fragestellung Spontanheilungen von Rupturen des vorderen Kreuzbandes (VKB) wurden wiederholt mittels MRT beschrieben. In grundlegenden tierexperimentellen Untersuchungen wird geschlussfolgert, dass es keine Regeneration gäbe. Die Morphologie der Spontanheilung des VKB wurde im Tiermodell des Kaninchens untersucht. Methoden 32 männliche Kaninchen wurden medial arthrotomiert und das VKB durchtrennt. Die Durchtrennung erfolgte unter Sicht mittels Nr. 15 Skalpell, zusätzlich wurde die vollständige Trennung der Stümpfe durch mehrfache Instrumentenpassage kontrolliert. Eine Resektion von Fasern erfolgte nicht. Je 8 Tiere wurden 2, 4, 8 und 12 Wochen nach dem Eingriff getötet. Die Morphologie der Heilungsverläufe wurde nach Lo et al. [1] klassifiziert, neue Typen der Klassifikation hinzugefügt. Typ B (intrasynoviale Ruptur) und Typ C (knöcherner Ausriss) waren studienbedingt nicht möglich. Die Studie war vom Regierungspräsidium genehmigt. Ergebnisse Die untersuchten Tiere hatten einen unauffälligen postoperativen Verlauf. Bei unterschiedlicher Ausprägung hatten alle Tiere makroskopisch eine Knorpelschädigung. Nach chirurgischer Durchtrennung waren die VKBenden durchschnitten (mop ended Typ A). Dieser Typ wurde bei der Dissektion nicht mehr vorgefunden. Die VKBstümpfe waren bei Dissektion: retrahiert (Typ D), mit dem hinteren Kreuzband verwachsen (E), resorbiert (F), miteinander verbunden = narbengeheilt (G), oder es lag eine Kombination (H) verschiedener Typen vor. Als neue Typen wurden Verwachsungen mit dem Meniskus (I) oder mit der Gelenkkapsel bzw. dem Fettkörper (K) beschrieben. Die VKBstümpfe waren gering (G 1 = 7), deutlich (G2 = 3 bzw. 4 insges. bei zusätzlicher Verwachsung mit dem Innenmeniskus) oder hypertroph (G 3 = 3) miteinander verwachsen. [Tab. 1] Schlussfolgerungen Der VKBriss führt häufig zur Kniegelenksinstabilität und Osteoarthrose. Nach Durchtrennung des VKB wird in Studien der Osteoarthroseforschung im Kaninchenmodell der Befund nie detailliert. In einem systematischen Vergleich der Regenerationsfähigkeit von partiell und komplett durchtrennten VKBs fanden Hefti et al. [2] weder bei skeletall unreifen noch bei jungen erwachsenen Kaninchen eine Regeneration nach kompletter Durchtrennung. Sie berichteten als Regelfall die Resorption nach 3 Monaten, in 2 Fällen Verwachsungen mit dem hinteren Kreuzband. Die hier berichteten Daten sind im Gegensatz zu Hefti's Untersuchungen. Sie stimmen aber gut mit humanen MRT-Untersuchungen und Arthroskopien nach Kreuzbandverletzungen überein. Das VKB versucht durch Verwachsung eine Heilung der VKBstümpfe zu erzielen oder Anschluss an andere Kniegelenksstrukturen zu gewinnen. Somit besteht auch im Tiermodell des Kaninchens eine gewisse Spontanheilungsaktivität des VKB, deren biomechanische Stabilität allerdings oft unzureichend erschien. Eine Kniegelenksarthrose entwickelte sich in den untersuchten Gelenken

Increase in degraded collagen type II in synovial fluid early in the rabbit meniscectomy model of osteoarthritis

SummaryObjectiveThe objective of this study was to determine whether collagen type II breakdown products in synovial fluid (SF), detected by an enzyme-linked immunoassay, represent a useful marker for early events in osteoarthritis (OA) in the rabbit medial meniscectomy model.DesignComplete medial meniscectomy was performed on the right knee joints of 32 rabbits. Balanced groups of rabbits were then sacrificed at 2, 4, 8, and 12 weeks post-surgery. An additional 8 unoperated and 11 sham-operated animals served as controls. SF lavages were performed on right and left knee joints of the same animals at sacrifice. The proteolytic epitope of type II collagen was monitored using an enzyme-linked immunoassay.ResultsMacroscopically visible surface fibrillation and focal erosions appeared as early as 2 weeks after meniscectomy in the femorotibial joint (P<0.01). OA developed gradually during the later observation period, and then predominantly on the medial tibial plateau and medial femur. Significant histological alterations in cartilage, including a loss of proteoglycans, surface irregularities, and clefts, were detected at 2 weeks after meniscectomy (P<0.01). Collagen type II epitope levels in SF lavage samples were elevated peaking at 2 weeks after meniscectomy (P<0.02). Levels decreased at later time points, but they were still raised at 12 weeks (P≤0.05). Highly significant correlations were found between the SF collagen type II epitope levels and the macroscopic and microscopic scoring results (Spearman rho correlation coefficient, macroscopy—collagen type II epitope r=0.222, P=0.025; microscopy—collagen type II epitope r=0.436, P≤0.01).ConclusionIn this rabbit model of medial meniscectomy, levels of type II collagen fragments in SF appear to provide a useful marker of the early degenerative changes

Anti-Mullerian-Hormone during pregnancy and peripartum using the new Beckman Coulter AMH Gen II Assay

Background: AMH levels determined by the conventional AMH assay declined during pregnancy and postpartum. A new Beckman Coulter AMH Gen II assay removes the potentially assay-interfering complement which is activated in pregnancy. The aim of this study was to evaluate if the decline of AMH levels in the serum of pregnant women during the course of pregnancy and peripartum was assay-dependent and thus artificial. Methods: In this cross-sectional study prepartal blood samples were collected from 62 patients (median age 30.6 years [interquartile range: 25.6 - 34.5]) in the third trimester of pregnancy and again 1–4 days after delivery between 2011 and 2012. In another cohort of 11 patients (median age 34.1 years [interquartile range: 32.6 - 37.8]) blood samples were taken in different trimesters of pregnancy between 1995 and 2001. The conventional and the modified AMH assay were performed in the same patient serum samples. We used the conventional and the modified AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. The Wilcoxon signed rank test was used for determining differences between AMH levels pre- and postpartum. The method of Bland and Altman was applied for analyzing the agreement of both methods for determining AMH levels. Results: AMH values peripartum were lower than those expected in fertile non-pregnant women of comparable age. An overall mean difference of 0.44 ng/ml was observed between the conventional and the modified assay. Measurements with the modified assay showed a significant decline of postpartal levels compared with prepartal levels which is consistent with values obtained using the conventional assay (both p < 0.00001). Compared to the longitudinal measurements of AMH levels determined using the conventional assay, AMH levels obtained using the modified assay suggest a steeper decline of values during the course of pregnancy. Conclusion: By comparing the conventional assay for AMH determination with the modified assay the present study confirmed that AMH levels decline during the course of pregnancy and early after delivery

Biochemisches Monitoring nach Meniskektomie

Fragestellung Die Schädigung des Kollagennetzwerks ist ein frühes Ereignis der Arthrose (OA). Wir untersuchten ein Kollagen Typ II -Neoepitop (CTX) in der Synovialflüssigkeit (SF) nach kompletter medialer Meniskektomie (ME). Methoden 32 NZW-Kaninchen hatten eine ME des rechten Kniegelenks. Kontrolle: 11 shamoperierte, 8 unoperierte Kaninchen. Die ME-Kaninchen wurden nach 2 (n = 8), 4 (n = 8) , 8 (n = 8) und 12 (n = 8) Wochen getötet, SF-lavagen beider Kniegelenke durchgeführt. Der ELISA misst ein Kollagen Typ II - Neoepitop, das nach Spaltung der C-telopeptide cross-linking Domaine entsteht. Makroskopisch: Grading beider Kniegelenke mit einem 9 Felder-Schema: Einzelflächen und Gesamtsummen von Tibia, Femur (jeweils medial und lateral) und Patella Histologisch: Grading mit H&E und Safranin O Schnitten (u.a. Proteoglykangehalt, Matrixstruktur, Zellularität, Tidemark und Osteophyten) Statistik: Wilcoxon - und Mann - Whitney U Test. Ergebnisse Makroskopisch: signifikante Veränderungen von medialer Tibia und Femur ab 2 Wochen nach ME, im Vergleich mit Gegenseite und mit nichtoperierten Kaninchen. Histologisch: beginnende OA zu allen Zeitpunkten. ME Knie: CTX Werte in der SF deutlich erhöht, zum kontralateralen Knie für 2, 4, 8 und 12 Wochen signifikant. Nichtoperierte Tiere: keine Unterschiede linkes vs. rechtes Knie, im Vergleich zur ME zu allen Zeitpunkten signifikant niedriger. Schlussfolgerungen Knorpelmarker sind Parameter der OA. Die Metalloproteinasen 1, 8 und 13 erzeugen ein Kollagen Typ II - Neoepitop, das zum Monitoring der arthrotischen Veränderungen geeignet erscheint

Probabilistic (logic) programming concepts

A multitude of different probabilistic programming languages exists today, all extending a traditional programming language with primitives to support modeling of complex, structured probability distributions. Each of these languages employs its own probabilistic primitives, and comes with a particular syntax, semantics and inference procedure. This makes it hard to understand the underlying programming concepts and appreciate the differences between the different languages. To obtain a better understanding of probabilistic programming, we identify a number of core programming concepts underlying the primitives used by various probabilistic languages, discuss the execution mechanisms that they require and use these to position and survey state-of-the-art probabilistic languages and their implementation. While doing so, we focus on probabilistic extensions of logic programming languages such as Prolog, which have been considered for over 20 years

Variable Compression in ProbLog

In order to compute the probability of a query, ProbLog represents the proofs of the query as disjunctions of conjunctions, for which a Reduced Ordered Binary Decision Diagram (ROBDD) is computed. The paper identifies patterns of Boolean variables that occur in Boolean formulae, namely AND-clusters and OR-clusters. Our method compresses the variables in these clusters and thus reduces the size of ROBDDs without affecting the probability. We give a polynomial algorithm that detects AND-clusters in disjunctive normal form (DNF) Boolean formulae, or OR-clusters in conjunctive normal form (CNF) Boolean formulae. We do an experimental evaluation of the effects of AND-cluster compression for a real application of ProbLog. With our prototype implementation we have a significant improvement in performance (up to 87%) for the generation of ROBDDs. Moreover, compressing AND-clusters of Boolean variables in the DNFs makes it feasible to deal with ProbLog queries that give rise to larger DNFs.acceptance rate: 38%status: publishe

Generating Random Logic Programs Using Constraint Programming

Testing algorithms across a wide range of problem instances is crucial to ensure the validity of any claim about one algorithm's superiority over another. However, when it comes to inference algorithms for probabilistic logic programs, experimental evaluations are limited to only a few programs. Existing methods to generate random logic programs are limited to propositional programs and often impose stringent syntactic restrictions. We present a novel approach to generating random logic programs and random probabilistic logic programs using constraint programming, introducing a new constraint to control the independence structure of the underlying probability distribution. We also provide a combinatorial argument for the correctness of the model, show how the model scales with parameter values, and use the model to compare probabilistic inference algorithms across a range of synthetic problems. Our model allows inference algorithm developers to evaluate and compare the algorithms across a wide range of instances, providing a detailed picture of their (comparative) strengths and weaknesses.Comment: This is an extended version of the paper published in CP 202

Symbolic Logic meets Machine Learning: A Brief Survey in Infinite Domains

The tension between deduction and induction is perhaps the most fundamental issue in areas such as philosophy, cognition and artificial intelligence (AI). The deduction camp concerns itself with questions about the expressiveness of formal languages for capturing knowledge about the world, together with proof systems for reasoning from such knowledge bases. The learning camp attempts to generalize from examples about partial descriptions about the world. In AI, historically, these camps have loosely divided the development of the field, but advances in cross-over areas such as statistical relational learning, neuro-symbolic systems, and high-level control have illustrated that the dichotomy is not very constructive, and perhaps even ill-formed. In this article, we survey work that provides further evidence for the connections between logic and learning. Our narrative is structured in terms of three strands: logic versus learning, machine learning for logic, and logic for machine learning, but naturally, there is considerable overlap. We place an emphasis on the following "sore" point: there is a common misconception that logic is for discrete properties, whereas probability theory and machine learning, more generally, is for continuous properties. We report on results that challenge this view on the limitations of logic, and expose the role that logic can play for learning in infinite domains