Volume 53, Issue 3

Operative joint replacement to treat disabling joint conditions secondary to degenerative and inflammatory arthritides has become one of the most efficacious and cost-effective procedures to relieve pain and restore joint function. However, prosthetic implants are not built to last forever and osteolysis and aseptic loosening has been associated with prosthetic arthroplasties since their introduction. The functional life of a synthetic joint is influenced by many factors including the material of the implant, operation procedures and the surgeon involved, as well as patient-related factors. Although promising developments have been achieved in this field, more than 10% of all implants still have to undergo operative revision within 15 years after the initial operation. Failure due to sepsis, fractures and dislocations has become rare; premature loosening of implants on the other hand is becoming much more important. Prosthetic loosening without concurrent infection or trauma is called aseptic loosening. It is generally accepted that small particles (“wear debris”) and activated macrophages play a key role in aseptic loosening. The pathophysiology of this condition, however, is still not very well characterized. In this article, we review the molecular mechanisms and signal pathways that were unravelled as responsible factors for loosening orthopaedic implants. Finally, we discuss possible novel strategies for future therapeutic approaches.

Background : Left cervical vagus nerve stimulation (VNS) using the implanted NeuroCybernetic Prosthesis (NCP ® ) can reduce epileptic seizures and has recently been shown to give promising results for treating therapy-resistant depression. To address a disadvantage of this state-of-the-art VNS device, the use of an alternative transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was studied. Functional magnetic resonance imaging (MRI) has been used to test non-invasively access nerve structures associated with the vagus nerve system. The results and their impact are unsatisfying due to missing brainstem activations. These activations, however, are mandatory for reasoning, higher subcortical and cortical activations of vagus nerve structures. The objective of this study was to test a new parameter setting and a novel device for performing specific (well-controlled) transcutaneous VNS (tVNS) at the inner side of the tragus. This paper shows the feasibility of these and their potential for brainstem and cerebral activations as measured by blood oxygenation level dependent functional MRI (BOLD fMRI). Materials and methods : In total, four healthy male adults were scanned inside a 1.5-Tesla MR scanner while undergoing tVNS at the left tragus. We ensured that our newly developed tVNS stimulator was adapted to be an MR-safe stimulation device. In the experiment, cortical and brainstem representations during tVNS were compared to a baseline. Results : A positive BOLD response was detected during stimulation in brain areas associated with higher order relay nuclei of vagal afferent pathways, respectively the left locus coeruleus, the thalamus (left≫right), the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated gyrus and the left insula. Deactivations were found in the right nucleus accumbens and the right cerebellar hemisphere. Conclusion : The method and device are feasible and appropriate for accessing cerebral vagus nerve structures, respectively. As functional patterns share features with fMRI BOLD, the effects previously studied with the NCP ® are discussed and new possibilities of tVNS are hypothesised. Zusammenfassung Hintergrund : Die Vagusnervstimulation am linken Halsstrang mit einer implantierten neurokybernetischen Prothese hat sich als suffizient bei der Behandlung von epileptischen Episoden erwiesen und zeigt zudem vielversprechende Behandlungsansätze für therapieresistente Depressionen. Aufgrund zahlreicher Nachteile einer derzeit alleinig verfügbaren implantologischen Lösung wurden in der letzten Zeit Studien zur Verwendung der transkutanen elektrischen Nervenstimulation, die hauptsächlich der Muskelstimulation dient, als nicht-invasiver Zugang zu Hirnstamm- und Kortexstrukturen über afferente Vagusnervfasern am menschlichen Ohr unter Verwendung der funktionellen Magnetresonanztomographie durchgeführt. Die Resultate und Folgerungen dieser Studien sind aber fragwürdig, da keine Aktivierungen des Hirnstamms ermittelt wurden. Diese allerdings sind für eine Aktivierung höherer Zentren unbedingt notwendig. Aufgabe der hier vorliegenden Arbeit war es daher, eine Methode und ein Gerät zur transkutanen Vagusnervstimulation (tVNS) an der Innenseite des Tragus zu entwickeln, welche auch eine solche Hirnstammaktiverung ermöglichen, und diese unter Zuhilfenahme des BOLD-Effekts (blood oxygenation level dependent functional magnetic resonance imaging, BOLD fMRI) basierend auf der funktionellen Magnetresonanztomographie zu studieren. Material und Methode : Vier männliche und gesunde Probanden wurden während tVNS an der linken Ohrmuschel in einem 1,5-Tesla-MR-Scanner untersucht. Hierfür wurde eine speziell konstruierte MR-taugliche Stimulationseinheit entwickelt und verwendet. In diesem Experiment wurden die BOLD-Effekte in Phasen während der Stimulation mit Ruhephasen ohne Stimulation verglichen. Ergebnisse : Positive BOLD-Effekte während der Stimulation traten insbesondere in Hirnarealen auf, welche Relais höherer Ordnung für vagale Afferenzen darstellen, wie dem Locus coeruleus, dem Thalamus (links≫rechts), dem linken präfrontalen Kortex, dem rechten und linken Gyrus postcentralis, dem linken hinteren Gyrus cinguli und der linken Inselregion. Deaktivierungen wurden im rechten Nucleus accumbens und der rechten Kleinhirnhemisphäre sichtbar. Schlussfolgerung : Vorgeschlagene Methode und Gerät können zerebrale Strukturen des Vagusnervsystems, insbesondere auch Hirnstammareale, aktivieren. Die Aktivierungsmuster unter tVNS ähneln jenen der zerebralen regionalen Blutflussänderungen aus früheren Studien unter Verwendung der NCP. Daher scheinen neue diagnostische und therapeutische Ansätze zumindest theoretisch möglich zu sein.

Differences in breast volume and contour are subjectively estimated by surgeons. 3D surface imaging using 3D scanners provides objective breast volume quantification, but precision and accuracy of the method requires verification. Breast volumes of five test individuals were assessed using a 3D surface scanner. Magnetic resonance imaging (MRI) reference volumes were obtained to verify and compare the 3D scan measurements. The anatomical thorax wall curvature was segmented using MRI data and compared to the interpolated curvature of the posterior breast volume delimitation of 3D scan data. MRI showed higher measurement precision, mean deviation (expressed as percentage of volume) of 1.10±0.34% compared to 1.63±0.53% for the 3D scanner. Mean MRI [right (left) breasts: 638 (629)±143 (138) cc] and 3D scan [right (left) breasts: 493 (497)±112 (116) cc] breast volumes significantly correlated [right (left) breasts: r=0.982 (0.977), p=0.003 (0.004)]. The posterior thorax wall of the 3D scan model showed high agreement with the MRI thorax wall curvature [mean positive (negative) deviation: 0.33 (-0.17)±0.37 cm]. High correspondence and correlation of 3D scan data with MRI-based verifications support 3D surface imaging as sufficiently precise and accurate for breast volume measurements.

Biomechanical tests of human femora have shown that small variations of the loading direction result in significant changes in measured bone mechanical properties. However, the heterogeneity in geometrical and bone tissue properties does not make human bones well suited to reproducibly assess the effects of loading direction on stiffness and strength. To precisely quantify the influence of loading direction on stiffness and strength of femora loaded at the femoral head, we tested femora from C57BL/6 inbred mice. We developed an image-based alignment protocol and investigated the loading direction influence on proximal femur stiffness and strength. An aluminum femoral phantom and C57BL/6 femora were tested under compression with different loading directions. Both tests, with the aluminum phantom and the murine bones, showed and quantified the linear dependence of stiffness on loading direction: a 5° change in loading direction resulted in almost 30% change in stiffness. Murine bone testing also revealed and quantified the variation in strength due to loading direction: 5° change in loading direction resulted in 8.5% change in strength. In conclusion, this study quantified, for the first time, the influence of misalignment on bone stiffness and strength for femoral head loading. We showed the extreme sensitivity of this site regarding loading direction.

Internal fixation of fractures of the proximal humerus needs a high stability of fixation to avoid secondary loss of fixation. This is especially important in osteoporotic bone. In an experimental study, the biomechanical properties of the angle-fixed Philos plate (internal fixator) and a double-plate osteosynthesis using two one-third tubular plates were assessed. The fracture model was an unstable three-part fracture (AO type B2). Eight pairs of human cadaveric humeri were submitted to axial load and torque. In the first part of the study, it was assessed to which degree the original stiffness of the humeri could be restored after the osteotomy by the osteosynthesis procedure. Subsequently, subsidence during 200 cycles of axial loading and torque was analysed. During axial loading, the Philos plate was significantly stiffer and showed less irreversible deformation. Two double-plate fixations, but none of the Philos plate osteosynthesis, failed. During torsion, there were no significant differences between the two implants. From the biomechanical point of view, the angle-fixed Philos plate represents the implant of choice for the surgical fixation of highly unstable three-part fractures of the proximal humerus, as the internal fixator system is characterised by superior biomechanical properties.

An increasing number of animal experiments are currently conducted on clinical MR systems. Motion artefacts due to breathing can become quite apparent, in particular with abdominal examinations. These artefacts can be reduced by using a triggered acquisition. However, the built-in detectors in human whole-body scanners are usually not sensitive enough to detect the tiny movements of small rodents. Therefore, a sensitive optical motion detector was developed together with a simple, robust analogue circuit. This circuit converts the original optical signal into an electrical one, compensates slow drifts and offsets, and finally generates a transistor-transistor logic trigger signal as input for the clinical whole-body magnetic resonance scanner. The trigger was successfully applied in mouse experiments. Zusammenfassung Tierexperimente werden immer häufiger auch an klinischen Ganzkörper-Magnetresonanz (MR)-Systemen durchgeführt. Gerade bei abdominellen Untersuchungen verursacht die Atembewegung der Kleinsäuger jedoch oft Bewegungsartefakte in den MR-Bildern. Diese Bewegungsartefakte können durch Triggerung der MR-Messung auf die Atembewegung deutlich reduziert werden. Allerdings sind die in den Scannern integrierten Atemdetektorsysteme in der Regel zu unempfindlich für Kleinsäuger, wie Mäuse oder Ratten. Daher wurde ein empfindlicher optischer Bewegungssensor zusammen mit einer einfachen, robusten Analogschaltung entwickelt. Diese Schaltung wandelt das optische Signal in ein elektrisches um, kompensiert langsame Drifts und Offsetspannungen und generiert ein Transistor-Transistor-Logic-Signal zur Triggerung des MR-Scanners. Der Trigger wurde erfolgreich an Mäusen getestet.

The aim of this study was to identify precursors of neurocardiogenic syncope (NCS) in ECG parameters of children and adolescents who undergo head-up tilt testing (HUTT). Established linear and non-linear parameters of heart rate variability (HRV) were calculated minute-by-minute in 44 young patients with an NCS history (age 7–20 years, 22 female, 22 male, positive HUTT) and 34 age-matched healthy controls (age 7–20 years, 17 female, 17 male, negative HUTT) during 60° HUTT. The influence of age and gender on the response to tilting was studied using the Wilcoxon rank sum test. We also assessed the predictive power of individual features with respect to HUTT outcome within three temporal windows (0–2 min after tilt; 2–5 min after tilt, and 5–2 min before tilt-back) by means of receiver operating characteristics analysis. Our results indicate that prediction of HUTT outcome should be restricted to subjects in or after puberty. In this group, descriptors based on co-occurrence or joint-recurrence analysis in recurrence plots showed promising predictive power (up to 86% sensitivity and 90% specificity, area under the curve 0.91). Time-domain parameters (standard deviation of differences for successive RR intervals) reached 75% sensitivity and 80% specificity. We conclude that HRV analysis within the first 5 min after tilting provides significant information on HUTT outcome and may be useful in conjunction with more sophisticated classification strategies for shortening HUTT duration in subjects after puberty.

A simple and non-intrusive approach termed the pulse transit time ratio (PTTR) has recently been shown to be a potential surrogate of the ankle-brachial index (ABI). PTTR is based on the principle of PTT, which is known to be temperature-sensitive. In this study, 23 healthy adults with normally perfused peripheries and 10 with poorly perfused peripheries were recruited. No significant change in PTTR was observed between those with cold (1.287±0.043) and normal (1.290±0.027) peripheries (p>0.05). A cold periphery may cause pulse waveform changes and indirectly affect PTT owing to poor skin microcirculation, but may have a limited effect on PTTR, which is useful as an ABI alternative.