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Open reduction and internal fixation with a locking plate are performed frequently to treat fractures of the proximal humerus. Avascular necrosis and non-union or malunion are potential complications of this procedure, which lead to specific fracture sequelae. The aim of this study was to investigate the clinical and radiological results of patients treated by removal of a failed locking plate of the proximal humerus and simultaneous implantation of a reverse total shoulder prosthesis. Twenty-one patients (f = 17, m = 4; mean age 70 years) out of 29 patients were available for follow-up after a mean period of 45 (30–65) months. At follow-up, all patients were assessed with the constant score and the ASES score as well as plain radiographs. In comparison with the preoperative values, abduction (31° vs. 115°; p

Die Alkaptonurie (Ochronose) ist eine autosomal-rezessiv vererbbare Storung des Tyrosinstoffwechsels. Mangelnder Abbau der Aminosaure Tyrosin verursacht eine Anreicherung der Homogentisinsaure. Die Oxidation der Homogentisinsaure fuhrt ab der 4. Dekade zu Ablagerungen des schwarzen ochronotischem Pigments im hyalinen Gelenkknorpel und dem gefasarmen Bindegewebe und verursacht progrediente degenerative Gelenkveranderungen. Der Fallbericht beschreibt einen 47-jahrigen mannlichen Patient, der trotz hochdosierter Schmerzmedikation und intensiver konservativer Therapie uber Schmerzen des linken Schultergelenks klagte. Nach einer initialen Arthroskopie mit Nachweis einer fortgeschrittenen Arthrose und grauschwarzen Knorpel- und Synovialgewebe wurde eine anatomische Schulterprothese implantiert. Die Diagnose Alkaptonurie wurde anhand des Laborbefunds mit 1,7 g/l Homogentisinsaure im Urin gestellt. Postoperativ konnten ein gutes Bewegungsausmas sowie eine Schmerzlinderung erzielt werden. Die Rontgenkontrolle zeigte einen regelrechten Sitz des Implantats. Der Fallbericht beschreibt das seltene Krankheitsbild Alkaptonurie mit einer Erstmanifestation am Schultergelenk. Die ausgepragte Symptomatik konnte durch die Implantation der Schulterprothese adaquat behandelt werden.

The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd.

The goal of this study was to identify alternative mechanisms of osteoarthritis pathology by analyzing subchondral bone. Femoral condyle samples were collected from post-menopausal female patients with knee osteoarthritis undegoing total knee arthroplasty. In the majority of patients, subchondral trabecular bone volume doubled under a region of the medial femoral condyle with full-thickness cartilage deterioration. However, in a subset of patients the bone volume in this region remained constant. This subset also had larger areas of vascular penetration in the calcified cartilage of the lateral condyle concurrent with increased vascular endothelial growth factor expression. Subtyping by subchondral bone characteristics identified a unique population, which lacked the sclerotic bone characteristic of late-stage osteoarthritis. Identification of subtypes within the osteoarthritis population allows investigation of alternate disease pathologies.

Lumbar total disc replacement (L-TDR) is a procedure used to relieve back pain and maintain mobility. Contemporary metal-on-polyethylene (MoP) L-TDRs were developed to address wear performance concerns about historical designs, but wear debris generation and periprosthetic tissue reactions for these newer implants have not been determined.The purpose of this study was to determine (1) whether periprosthetic ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris and biological responses were present in tissues from revised contemporary MoP L-TDRs that contain conventional cores fabricated from γ-inert-sterilized UHMWPE; (2) how fixed- versus mobile-bearing design affected UHMWPE wear particle number, shape, and size; and (3) how these wear particle characteristics compare with historical MoP L-TDRs that contain cores fabricated from γ-air-sterilized UHMWPE.We evaluated periprosthetic tissues from 11 patients who received eight fixed-bearing ProDisc-L and four mobile-bearing CHARITÉ contemporary L-TDRs with a mean implantation time of 4.1 and 2.7 years, respectively. Histologic analysis of tissues was performed to assess biological responses and polarized light microscopy was used to quantify number and size/shape characteristics of UHMWPE wear particles from the fixed- and mobile-bearing devices. Comparisons were made to previously reported particle data for historical L-TDRs.Five of seven (71%) fixed-bearing and one of four mobile-bearing L-TDR patient tissues contained at least 4 particles/mm(2) wear with associated macrophage infiltration. Tissues with wear debris were highly vascularized, whereas those without debris were more necrotic. Given the samples available, the tissue around mobile-bearing L-TDR was observed to contain 87% more, 11% rounder, and 11% less-elongated wear debris compared with tissues around fixed-bearing devices; however, there were no significant differences. Compared with historical L-TDRs, UHMWPE particle number and circularity for contemporary L-TDRs were 99% less (p = 0.003) and 50% rounder (p = 0.003).In this preliminary study, short-term results suggest there was no significant influence of fixed- or mobile-bearing designs on wear particle characteristics of contemporary L-TDRs, but conventional UHMWPE has notably improved the wear resistance of these devices compared with historical UHMWPE.

The enhanced differentiation of mesenchymal cells into chondrocytes or osteoblasts is of paramount importance in tissue engineering and regenerative therapies. A newly emerging body of evidence demonstrates that appendage regeneration is dependent on reactive oxygen species (ROS) production and signaling. Thus, we hypothesized that mesenchymal cell stimulation by nonthermal (NT)-plasma, which produces and induces ROS, would (1) promote skeletal cell differentiation and (2) limb autopod development. Stimulation with a single treatment of NT-plasma enhanced survival, growth, and elongation of mouse limb autopods in an in vitro organ culture system. Noticeable changes included enhanced development of digit length and definition of digit separation. These changes were coordinated with enhanced Wnt signaling in the distal apical epidermal ridge (AER) and presumptive joint regions. Autopod development continued to advance for approximately 144 h in culture, seemingly overcoming the negative culture environment usually observed in this in vitro system. Real-time quantitative polymerase chain reaction analysis confirmed the up-regulation of chondrogenic transcripts. Mechanistically, NT-plasma increased the number of ROS positive cells in the dorsal epithelium, mesenchyme, and the distal tip of each phalange behind the AER, determined using dihydrorhodamine. The importance of ROS production/signaling during development was further demonstrated by the stunting of digital outgrowth when anti-oxidants were applied. Results of this study show NT-plasma initiated and amplified ROS intracellular signaling to enhance development of the autopod. Parallels between development and regeneration suggest that the potential use of NT-plasma could extend to both tissue engineering and clinical applications to enhance fracture healing, trauma repair, and bone fusion.

PURPOSE To determine whether particulate debris is present in periprosthetic tissue from revised Dynesys(®) devices, and if present, elicits a biological tissue reaction. METHODS Five Dynesys(®) dynamic stabilization systems consisting of pedicle screws (Ti alloy), polycarbonate-urethane (PCU) spacers and a polyethylene-terephthalate (PET) cord were explanted for pain and screw loosening after a mean of 2.86 years (1.9-5.3 years). Optical microscopy and scanning electron microscopy were used to evaluate wear, deformation and surface damage, and attenuated total reflectance Fourier transform infrared spectroscopy to assess surface chemical composition of the spacers. Periprosthetic tissue morphology and wear debris were determined using light microscopy, and PCU and PET wear debris by polarized light microscopy. RESULTS All implants had surface damage on the PCU spacers consistent with scratches and plastic deformation; 3 of 5 exhibited abrasive wear zones. In addition to fraying of the outer fibers of the PET cords in five implants, one case also evidenced cord fracture. The pedicle screws were unremarkable. Patient periprosthetic tissues around the three implants with visible PCU damage contained wear debris and a corresponding macrophage infiltration. For the patient revised for cord fracture, the tissues also contained large wear particles (>10 μm) and giant cells. Tissues from the other two patients showed comparable morphologies consisting of dense fibrous tissue with no inflammation or wear debris. CONCLUSIONS This is the first study to evaluate wear accumulation and local tissue responses for explanted Dynesys(®) devices. Polymer wear debris and an associated foreign-body macrophage response were observed in three of five cases.

Few complications have been reported for lumbar total disc replacement (TDR) and hybrid TDR fixations. This study evaluated retrieved implants and periprosthetic tissue reactions for two cases of osteolysis following disc arthroplasty with ProDisc-L prostheses. Implants were examined for wear and surface damage, and tissues for inflammation, polyethylene wear debris (polarized light microscopy) and metal debris (energy-dispersive X-ray spectroscopy). Despite initial good surgical outcomes, osteolytic cysts were noted in both patients at vertebrae adjacent to the implants. For the hybrid TDR case, heterotopic ossification and tissue necrosis due to wear-induced inflammation were observed. In contrast, the non-hybrid implant showed signs of abrasion and impingement, and inflammation was observed in tissue regions with metal and polyethylene wear debris. In both cases, wear debris and inflammation may have contributed to osteolysis. Surgeons using ProDisc prostheses should be aware of these rare complications.

Total disc replacement was clinically introduced to reduce pain and preserve segmental motion of the lumbar and cervical spine. Previous case studies have reported on the wear and adverse local tissue reactions around artificial prostheses, but it is unclear how design and biomaterials affect clinical outcomes.Which design and material factors are associated with differences in clinical wear performance (implant wear and periprosthetic tissue response) of (1) lumbar and (2) cervical total disc replacements?We performed a systematic review on the topics of implant wear and periprosthetic tissue response using an advanced search in MEDLINE and Scopus electronic databases. Of the 340 references identified, 33 were retrieved for full-text evaluation, from which 16 papers met the inclusion criteria (12 on lumbar disc replacement and five on cervical disc replacement; one of the included studies reported on both lumbar and cervical disc replacement), which involved semiquantitative analysis of wear and adverse local tissue reactions along with a description of the device used. An additional three papers were located by searching bibliographies of key articles. There were seven case reports, three case series, two case-control studies, and seven analytical studies. The Methodological Index for Non-randomized Studies (MINORS) Scale was used to score case series and case-control studies, which yielded mean scores of 10.3 of 16 and 17.5 of 24, respectively. In general, the case series (three) and case-control (two) studies were of good quality.In lumbar regions, metal-on-polymer devices with mobile-bearing designs consistently generated small and large polymeric wear debris, triggering periprosthetic tissue activation of macrophages and giant cells, respectively. In the cervical regions, metal-on-polymer devices with fixed-bearing designs had similar outcomes. All metal-on-metal constructs tended to generate small metallic wear debris, which typically triggered an adaptive immune response of predominantly activated lymphocytes. There were no retrieval studies on one-piece prostheses.This review provides evidence that design and biomaterials affect the type of wear and inflammation. However, clinical study design, followup, and analytical techniques differ among investigations, preventing us from drawing firm conclusions about the relationship between implant design and wear performance for both cervical and lumbar total disc replacement.

This study investigated the hypothesis that wear particle-induced oxidative stress initiates osteolysis after total hip arthroplasty (THA). Patient radiographs were scored for osteolysis and periprosthetic tissues were immunostained and imaged to quantify polyethylene wear, inflammation, and five osteoinflammatory and oxidative stress-responsive factors. These included high mobility group protein-B1 (HMGB1), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), 4-hydroxynonenal (4-HNE), and nitrotyrosine (NT). The results show wear debris correlated with inflammation, 4-HNE, NT and HMGB1, whereas inflammation only correlated with NT and HMGB1. Similar to wear debris and inflammation, osteolysis correlated with HMGB1. Additionally, osteolysis correlated with COX2 and 4-HNE, but not iNOS or NT. Understanding the involvement of oxidative stress in wear-induced osteolysis will help identify diagnostic biomarkers and therapeutic targets to prevent osteolysis after THA.

The histology of periprosthetic tissue from metal-on-metal (MOM) hip devices has been characterized using a variety of methods. The purpose of this study was to compare and evaluate the suitability of two previously developed aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) scoring systems for periprosthetic hip tissue responses retrieved from MOM total hip replacement (THR) systems revised for loosening. Two ALVAL scoring systems (Campbell and Oxford) were used to perform histological analyses of soft tissues from 17 failed MOM THRs. The predominant reactions for this patient cohort were macrophage infiltration and necrosis, with less than half of the patients (41%) showing a significant lymphocytic response or a high ALVAL reaction (6%). Other morphological changes varied among patients and included hemosiderin accumulation, cartilage formation, and heterotopic ossification. Both scoring systems are useful for correlating macrophage and lymphocyte responses and for comparison with the other; however, given the diversity and variability of the current responses, the Oxford-ALVAL system is more suitable for scoring tissues from MOM THR patients revised for loosening. It is important that standardized methods of scoring MOM tissue responses be used consistently so multiple study results can be compared and a consensus can be generated.

The purpose of this study was to analyze explanted PEEK rod spinal systems in the context of their clinical indications. We evaluated damage to the implant and histological changes in explanted periprosthetic tissues. 12 patients implanted with 23 PEEK rods were revised between 2008 and 2012. PEEK rods were of the same design (CD Horizon Legacy, Medtronic, Memphis TN, USA). Retrieved components were assessed for surface damage mechanisms, including plastic deformation, scratching, burnishing, and fracture. Patient history and indications for PEEK rod implantation were obtained from analysis of the medical records. 11/12 PEEK rod systems were employed for fusion at one level, and motion preservation at the adjacent level. Surgical complications in the PEEK cohort included a small dural tear in one case that was immediately repaired. There were no cases of PEEK rod fracture or pedicle screw fracture. Retrieved PEEK rods exhibited scratching, as well as impressions from the set screws and pedicle screw saddles. PEEK debris was observed in two patient tissues, which were located adjacent to PEEK rods with evidence of scratching and burnishing. This study documents the surface changes and tissue reactions for retrieved PEEK rod stabilization systems. Permanent indentations by the set screws and pedicle screws were the most prevalent observations on the surface of explanted PEEK rods.

Background The purpose of this study was to evaluate wear debris in periprosthetic tissues at the time of revision total elbow arthroplasty. Polyethylene, metallic, and bone cement debris were characterized, and the tissue response was quantified. Materials and methods Capsular and medullary tissue samples were collected during revision surgery. Polyethylene debris was characterized by scanning electron microscopy after tissue digestion. The concentrations of metal and cement debris were quantified by inductively coupled plasma mass spectrometry. Tissue response was graded with a semiquantitative histologic method. Results Polyethylene particle size varied from the submicron range to over 100 μm. The mean diameter ranged from 0.6 μm to about 1 μm. Particles in the synovial tissues were larger and less abundant than those in tissues from the medullary canal. Cement, titanium alloy, and low levels of cobalt-chrome debris were also present, with cement predominating over metal debris. Histiocyte response was associated with small polyethylene particles (0.5-2 μm), and giant cells were associated with large polyethylene particles (>2 μm). Histiocyte scores positively correlated with the polyethylene particle number and the presence of metal. Discussion We have shown that periprosthetic tissues of total elbow patients who have undergone revision for loosening and osteolysis contain polyethylene, cement, and metal debris. Although the polyethylene particles were of a size and shape that have been previously shown to result in activation of phagocytic cells, osteolysis after total elbow arthroplasty is a multimodal process. Because of the presence of multiple wear particle sources, a cause-and-effect relationship between polyethylene debris and osteolysis cannot be established with certainty.

Die inverse Schulterprothese hat sich in Orthopadie und Unfallchirurgie etabliert. Bei steigenden Implantationszahlen erhalten auch Therapie und Prophylaxe auftretender Komplikationen einen erhohten Stellenwert. Die Ermudungsfraktur der Spina scapulae und des Akromions ist mit 2–15 % eine nicht selten auftretende Komplikation. Eine standardisierte Therapie gibt es aktuell nicht und die Ergebnisse sind haufig unbefriedigend. Mit dem Ziel einer schnelleren Rehabilitation und Schmerzfreiheit sowie eines besseren funktionellen Ergebnisses im Vergleich zur konservativen Therapie fuhrten wir bei dislozierten Frakturen der Typen II und III eine offen chirurgische Reposition und Plattenosteosynthese durch. In der 1-Jahres-Kontrolle zeigte sich eine sehr gute Reduktion der Schmerzen. In Bezug auf Kraft und Beweglichkeit fanden sich jedoch im Vergleich zu Patienten ohne stattgehabte Fraktur deutliche Defizite. Trotz der objektiv schlechten Ergebnisse waren 5 der 6 behandelten Patienten nach osteosynthetischer Versorgung insgesamt zufrieden. Bei Revisionseingriffen besteht ein deutlich erhohtes Risiko fur das Auftreten solcher Frakturen. Konversionsoperationen zeigten in unserem Patientenkollektiv ein besonders hohes Frakturrisiko. Gerade in diesen Fallen scheint ein sorgfaltiges Weichteilmanagement mit ausgiebigem Release essenziell. Ob durch moderne Prothesendesigns mit austauschbaren Prothesenmetaphysen zukunftig das Frakturrisiko minimiert werden kann, bleibt abzuwarten.

The pathophysiology and mechanisms driving the generation of unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce inflammation, which may result in pain.The purpose of this study was to determine whether (1) periprosthetic UHMWPE wear debris induces immune responses that lead to the production of tumor necrosis factor-α (TNFα) and interleukin (IL)-1ß, the vascularization factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGFbb), and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2) the number of macrophages is associated with the production of the aforementioned factors; (3) the wear debris-induced inflammatory pathogenesis involves an increase in vascularization and associated innervation.Periprosthetic tissues from our collection of 11 patients with contemporary TDRs were evaluated using polarized light microscopy to quantify UHMWPE wear particles. The major reason for revision (mean implantation time of 3 years [range, 1-6 years]) was pain. For control subjects, biopsy samples from four patients with degenerative disc disease with severe pain and autopsy samples from three normal patients with no history of back pain were also investigated. Immunohistochemistry and histology were used to identify secretory factors, macrophages, and blood vessels. Immunostained serial sections were imaged at ×200 magnification and using MATLAB and NIH ImageJ, a threshold was determined for each factor and used to quantify positive staining normalized to tissue sectional area. The Mann-Whitney U test was used to compare results from different patient groups, whereas the Spearman Rho test was used to determine correlations. Significance was based on p0.05.The mean percent area of all six inflammatory, vascularization, and innervation factors was higher in TDR tissues when compared with normal disc tissues. Based on nonparametric data analysis, those factors showing the most significant increase included TNFα (5.17 ± 1.76 versus 0.05 ± 0.03, p = 0.02), VEGF (3.02 ± 1.01 versus 0.02 ± 0.002, p = 0.02), and substance P (4.15 ± 1.01 versus 0.08 ± 0.04, p = 0.02). The mean percent area for IL-1ß (2.41 ± 0.66 versus 0.13 ± 0.13, p = 0.01), VEGF (3.02 ± 1.01 versus 0.34 ± 0.29, p = 0.04), and substance P (4.15 ± 1.01 versus 1.05 ± 0.46, p = 0.01) was also higher in TDR tissues when compared with disc tissues from patients with painful degenerative disc disease. Five of the factors, TNFα, IL-1ß, VEGF, NGF, and substance P, strongly correlated with the number of wear particles, macrophages, and blood vessels. The most notable correlations included TNFα with wear particles (p0.001, ρ = 0.63), VEGF with macrophages (p = 0.001, ρ = 0.71), and NGF with blood vessels (p0.001, ρ = 0.70). Of particular significance, the expression of PDGFbb, NGF, and substance P was predominantly localized to blood vessels/nerve fibers.These findings indicate wear debris-induced inflammatory reactions can be linked to enhanced vascularization and associated innervation/pain factor production at periprosthetic sites around TDRs. Elucidating the pathogenesis of inflammatory particle disease will provide information needed to identify potential therapeutic targets and treatment strategies to mitigate pain and potentially avoid revision surgery.Level III, therapeutic study.

Is reverse total shoulder arthroplasty a feasible treatment option for failed shoulder arthroplasty? A retrospective study of 44 cases with special regards to stemless and stemmed primary implants.Due to humeral or glenoid bone-loss and rotator cuff insufficiency reverse total shoulder arthroplasty often means the only remaining treatment option in revision shoulder arthroplasty. This study investigates the clinical outcome of patients treated with a reverse total shoulder in revision cases with special regard to stemless and stemmed primary implants.From 2010 to 2012 60 failed shoulder arthroplasties were converted to reverse total shoulder arthroplasty. Forty-four patients were available for follow-up after a mean of 24 months. Patients were assessed with X-rays, Constant- and ASES Score and a questionnaire about their subjective satisfaction.The total number of observed complications was seven (16%). Ninety-eight percent of the patients were satisfied with their clinical result. Patients achieved a mean normalized constant score of 70.2% and a mean ASES Score of 65.3. Patients with stemless primary implants achieved a higher normalized constant score than patients with stemmed primary implants (82 vs. 61.8%; p = 0009).Reverse total shoulder arthroplasty provides satisfactory clinical results and a high patient satisfaction in revision shoulder arthroplasty. The complication rate needs to be considered and discussed with the patient prior to surgery. Presence or absence of a stem of revised shoulder arthroplasties interferes with the outcome. LEVEL OF EVIDENCE IV: (Retrospective study).

From a clinical perspective, implants for total joint replacement must contribute to a biologically favorable and mechanically stable environment to provide a satisfactory long-term outcome. One of the most important factors determining the success of a total joint replacement is implant wear over time and the associated adverse biologic reactions elicited by wear debris. The most obvious gross, clinical manifestation associated with implant wear debris generation is bone loss (osteolysis typically after 5–10 years), which has been identified as a major reason for implant loosening and the need for revision surgery after total hip replacement. In 1977, a seminal paper by Hans-Georg Willert demonstrated macrophage activation by UHMWPE wear debris that is generated by intended motion of the articulating implant surfaces, and by the movement of the implant against surrounding bone. These initial observations led to numerous studies characterizing the chronic inflammatory response to foreign debris accumulation in periprosthetic tissue. The challenge in assessing the pathophysiologic response to wear debris associated with a joint implant is to accurately characterize UHMWPE wear debris (amount, size, and shape) and the surrounding tissue response at both early and late implantation times.

Submicron sized particles are frequently observed in retrieved total hip and knee periprosthetic tissues and appear to be critical in the activation of the phagocytic inflammatory response. In this paper the concentration, size and shape of ultra-high molecular weight polyethylene (UHMWPE) wear particles between 0.05 and 2.00 mu m were determined after isolation from periprosthetic tissues from retrieved lumbar SB Charite III total disc replacements (TDR) using scanning electron microscopy (SEM). For comparison, UHMWPE wear particles were isolated from gamma-radiation-air sterilized total hip arthroplasty (THA) revision tissues. The mean concentration of UHMWPE particles in TDR tissues was 1.6 x 10(9) g(-1) tissue (range 1.3-2.0), which was significantly lower than the concentration of 2.3 x 10(9) g(-1) THA revision tissue (range 1.8-3.2) (P = 0.03). The mean particle size (equivalent circular diameter: TDR, 0.46 mu m; THA 0.53 mu m, P = 0.60) and mean shape were comparable between TDR and THA (aspect ratio: TDR, 1.89; THA, 1.99, P = 0.35; roundness: TDR, 0.58; THA, 0.56, P = 0.35). However, the TDR particles tended to be smaller and more round. Although no correlations were found between visible damage to the UHMWPE core and the concentration or shape of the UHMWPE particles, a positive correlation was found between increasing particle size and increasing rim penetration of the TDR core (P = 0.04). The presence of UHMWPE particles of similar size and shape in TDR tissue, albeit lower in concentration, might explain why, unlike THA, pain rather than osteolysis is the major reason for revision surgery.

Zur Behandlung der Ellenbogengelenksteife hat sich in den letzten Jahren die offene Arthrolyse uber den lateralen Zugang bewahrt. Um die klinischen Ergebnisse der mit dieser Methode behandelten Patienten zu beurteilen, wurden die aktuelle Literatur und die Studienlage mit besonderem Augenmerk auf die postoperative Beweglichkeit und Patientenzufriedenheit untersucht und verglichen. Eine Verbesserung dieser Parameter konnte insbesondere bei posttraumatischen Ellenbogengelenksteifen mit Kontrakturen der Gelenkkapsel und nur geringer Beeintrachtigung intraartikularer Strukturen festgestellt werden. Eine exakte Indikationsstellung ist somit Grundvoraussetzung fur einen erfolgreichen Therapieverlauf.

This article reviews certain practical aspects of retrieval analysis for motion preserving spinal implants and periprosthetic tissues as an essential component of the overall revision strategy for these implants. At our institution, we established an international repository for motion-preserving spine implants in 2004. Our repository is currently open to all spine surgeons, and is intended to be inclusive of all cervical and lumbar implant designs such as artificial discs and posterior dynamic stabilization devices. Although a wide range of alternative materials is being investigated for nonfusion spine implants, many of the examples in this review are drawn from our existing repository of metal-on-polyethylene, metal-on-metal lumbar total disc replacements (TDRs), and polyurethane-based dynamic motion preservation devices. These devices are already approved or nearing approval for use in the United States, and hence are the most clinically relevant at the present time. This article summarizes the current literature on the retrieval analysis of these implants and concludes with recommendations for the development of new test methods that are based on the current state of knowledge of in vivo wear and damage mechanisms. Furthermore, the relevance and need to evaluate the surrounding tissue to obtain a complete understanding of the biological reaction to implant component corrosion and wear is reviewed.

There is considerable interest in characterization of wear debris from polyethylene (UHMWPE) bearing components used in total joint replacement. To isolate UHMWPE wear debris, tissue samples must be excised from regions adjacent to revised UHMWPE implant components, followed by exposure to one of many available tissue digestion methods. Numerous studies demonstrate successful digestion, but the relative efficiency of each method is not clear. The purpose of this study was to evaluate a variety of conditions for tissue digestion to provide a quantitative comparison of methods. Porcine and human hip tissues were exposed for 24 h to basic, acidic or enzymatic agents, filtered and digestion efficiency calculated based on the percentage of initial to final tissue weight. Of the conditions tested, 5 M NaOH, 5 M KOH, 15 M KOH or 15.8 M HNO3 yielded the most complete porcine hip tissue digestion (

Study Design: We retrieved a functioning ProDisc-L total disc replacement and associated tissues at 16 months of service life. Objective: To analyze a previously unreported mode of implant malpositioning, wear mechanisms, and polyethylene locking mechanism, and to study retrieved periprosthetic tissues. Summary of Background Data: The clinical performance of polyethylene in the context of total disc replacements remains poorly understood. In the ProDisc-L, the polyethylene core is fixed to the inferior metal endplate through a mechanical interference locking mechanism similar to those used in tibial total knee components. This case represents the third report of an explanted ProDisc-L prosthesis, and the first reported case of posterior malpositioning with this device. Methods: The implant was removed via a transperitoneal approach. Its polyethylene core was evaluated for burnishing, fracture, third-body abrasion, and permanent deformation. An identical, never-implanted set of polyethylene and endplate components served as controls for the microscopic evaluation of wear. Two tissue samples were collected from a region adjacent to the failed implant to evaluate tissue morphology and inflammation. Hematoxylin and eosin-stained tissue sections were also evaluated for the presence of polyethylene debris by polarized light microscopy. Results: The implant was removed without serious incident, although there were incidental venotomies. The patient went on to solid arthrodesis. We found minimal wear, oxidation, and periprosthetic tissue reaction, as might be expected given the short-term duration of implantation and its reason for revision. No evidence was found of malfunction or improper deployment of the locking mechanism. Burnishing seemed to be the result of short-term impingement. Some areas of the tissue matrix showed evidence of early cell degeneration, and some of these areas contained polyethylene particles identified by polarized light microscopy. Conclusions: A larger series of implant retrievals will be needed to investigate possible wear and the biologic response to increased particle generation.

Patienten mit artikularseitigen Partialrupturen der Supraspinatussehne und zu Grunde liegendem Impingement werden in der Regel mit einer endoskopisch subakromialen Dekompression ohne Sehnenrekonstruktion behandelt, wenn das Ausmas der Partialruptur 50% der Sehnendicke nicht uberschreitet. Dieses Vorgehen wird in Hinblick auf einen moglichen Progress zur Komplettruptur mit schlechtem klinischem Ergebnis in Frage gestellt. Unsere Hypothese war, dass eine subakromiale Dekompression ohne Rekonstruktion der Supraspinatussehne zu einer signifikanten klinischen Verbesserung bei Patienten mit Grad-I- und Grad-II-Partialrupturen fuhrt, ohne dass es zu einem regelmasigen Fortschreiten zur Komplettruptur kommt. 46 konsekutive Patienten (durchschnittliches Alter 59,2 Jahre, 33–76,6 Jahre) wurden retrospektiv mit einem durchschnittlichen Follow-up von 50,3 Monaten (36–86 Monate) nachuntersucht. 26 Patienten (43,5%) zeigten eine Partialruptur Grad I nach Ellman, 20 Patienten eine Grad-II-Partialruptur, die mit einem intraartikularen Debridement behandelt wurde. Als Parameter fur das klinische Ergebnis diente der ASES-Score. Zusatzlich wurden alle Patienten einer standardisierten Ultraschalluntersuchung unterzogen, um eine mogliche Progredienz zur Komplettruptur zu identifizieren. Der durchschnittliche ASES-Score verbesserte sich signifikant von 37,4 auf 86,6 Punkte (p

Die Behandlung der traumatischen vorderen Schulterinstabilitat hat in den vergangenen 2 Jahrzehnten haufig kontroverse Diskussionen verursacht. Einigkeit herrscht jedoch uber die Notwendigkeit einer dem Verletzungsmechanismus, dem Auspragungsgrad der vorliegenden Instabilitat und dem Funktionsanspruch des Patienten in Bezug auf Beruf und Sport individuell angepassten Behandlung. Die offene Rekonstruktion des ventralen Kapsel-Labrum-Komplexes galt uber lange Jahre als Therapie der Wahl. Mittlerweile zeigen die Ergebnisse nach arthroskopischer Kapsel-Labrum-Refixation eine zunehmende Annaherung an die Ergebnisse der offenen Techniken. Insbesondere durch den Einsatz von Fadenankern scheint es moglich, die Prinzipien der klassischen offenen Bankart-Operation zu imitieren und so die allgemeinen Vorteile arthroskopischer Operationstechniken mit einer niedrigen Rezidivrate zu kombinieren.

The regional bone bank offers a good foundation for covering the expanding clinical demands in tumor and revision surgery. Since 1980 the tissue bank of Munster consists of 32 cadaveric and 41 multi organ donors. In the guidelines of the tissue bank the responsibility, organisation form, donor selection, quality control, sterilisation, documentation and all questions of finances are fixed, in accordance to the American Association of Tissue Banks. A fixed staff will be helpful to offer a secure and not expensive donor tissue for the clinical demands.

Der Schulterendoprothetik kommt in der orthopadischen Chirurgie eine zunehmende Bedeutung zu. Durch eine kontinuierliche Weiterentwicklung der Schulterprothesen gelingt es mit den aktuellen Prothesen die ursprungliche Anatomie der Schulter so exakt wie moglich zu rekonstruieren. Dies ist von entscheidender Bedeutung zur langfristigen Wiederherstellung von physiologischen Bewegungsmustern und zum Erreichen einer Schmerzreduktion. Die aktuellen Schaftkomponenten bieten die Moglichkeit die wichtigen Parameter Ante-/Retroversion, Inklination und Offset an der Prothese einzustellen, sodass eine Anpassung der Prothese an die vorgegebene Anatomie moglich ist. Fur die Glenoidkomponente ist die Verankerung von entscheidender Bedeutung, da der geringe Knochenstock diese erschwert. Zementierte Systeme stellen hier nach wie vor den Standard dar. Fur junge Patienten bietet der Oberflachenersatz eine sinnvolle Alternative zur Behandlung fruher Stadien der Arthrose. Bei der Defektarthropathie kommt die inverse Prothese zum Einsatz. Durch die Umkehrung des anatomischen Verhaltnisses zwischen Glenoid und Humerus kommt es zur Medialisierung und Kaudalisierung des Rotationszentrums und zur Vorspannung des M. deltoideus. Aufgrund der hohen Komplikationsrate sollte die Anwendung dem erfahrenen Spezialisten vorbehalten bleiben.

Die Beurteilung der Fragestellung, ob eine Beschwerdesymptomatik und Funktionsbeeintrachtigung aufgrund einer Schulterinstabilitat auf einen Unfall zuruckzufuhren ist, erfolgt unter Berucksichtigung der moglichen Ursachen der Instabilitat und unter Heranziehung unfallnaher sowie im weiteren Verlauf erhobener klinischer, radiologischer und ggf. intraoperativer Befunde, Informationen zur Vorgeschichte und zum Unfallhergang. Bedeutung beizumessen ist auch den klinischen Funktionstests zum Zeitpunkt der gutachtlichen klinischen Untersuchung. Es muss eine zusammenschauende Beurteilung unter Berucksichtigung samtlicher Kriterien vorgenommen werden. Diese Kriterien und ein entsprechendes Pro-Contra-Konzept sowie eine Empfehlung zur Einschatzung der Funktionsbeeintrachtigung werden im Folgenden vorgestellt.

The dynamic development of highly accurate optical measuring machines within the last years pushed the introduction of digitizing techniques to many applications in the fields of quality control, reverse engineering and rapid prototyping. By projecting fringe patterns onto the object's surface and recording pictures of the curvature dependant deformation of the pattern, 3D coordinates for each camera pixel are calculated on the basis of the principle of triangulation. The generation of a polygon mesh can be used for the analysis of the deviation of a die or a formed part to the initial CAD data, i.e. by means of full field or section based comparison. This paper presents the application of the above mentioned techniques on a double sheet hydroforming process. The gathered 3D data of the clam-shell part as well as of the tooling dies served for the calculation of the deviation to the respective reference geometry. With respect to the utilization of digitized tooling data within the finite element analysis, further investigations were performed on the impact of data reduction strategies. Aiming on the minimization of the necessary number of elements, representing the tooling surface in a discrete state, and on the request for a sufficient degree of accuracy, these strategies have to be considered of high priority.

Stiffness following total knee arthroplasty is a disabling complication1-7. Although some predisposing factors have been identified, in most cases the exact etiology of the stiffness cannot be discerned. The reported prevalence of this complication has ranged widely from 1.3% to 12%1,8-10. The difference in rate may be due in part to varied definitions of stiffness11. Several factors affecting the postoperative range of motion that have been identified include the preoperative range of motion, contracture of the extensor mechanism and capsular structure, the preoperative diagnosis, personality of the patient, lack of patient compliance with the rehabilitation protocol, and the patient's threshold for pain12-18. Technical factors, such as overstuffing the patellofemoral joint, mismatch of the flexion and extension gaps, inaccurate ligament balancing, component malpositioning, use of oversized components, joint-line elevation, excessive tightening of the extensor mechanism, and underresection of the patella have also been implicated1,19. Various management protocols have been proposed to address this complication. This exhibit presents our institutional experience with the management of stiffness following total knee arthroplasty. We report the findings of a case-control study that was designed to predict the factors responsible for stiffness after total knee arthroplasty. In addition, the results of an ongoing basic-science study attempting to unravel the molecular mechanism of arthrofibrosis following total knee arthroplasty are presented. We also provide the outline of our current treatment strategy for the management of stiffness following total knee arthroplasty. Fig. 1 Demographic distribution of patients in the study and control groups. TKA = total knee arthroplasty, and BMI = body-mass index. ### Case-Control Study The purpose of this study was to identify factors that predispose patients to stiffness following total knee arthroplasty. With use of an institutional computerized database, the outcome of …

Die Behandlung der traumatischen vorderen Schulterinstabilitat hat in den vergangenen zwei Jahrzehnten haufig kontroverse Diskussionen verursacht. Einigkeit herrscht jedoch uber die Notwendigkeit einer dem Verletzungsmechanismus, dem Auspragungsgrad der vorliegenden Instabilitat und dem Funktionsanspruch des Patienten in Bezug auf Beruf und Sport individuell angepassten Behandlung. Verschiedene offene und arthroskopische Techniken zahlen zu den gangigen Operationsverfahren. Dabei sollte das Ziel jedes operativen Stabilisierungsverfahrens die Wiederherstellung einer optimalen Balance zwischen Schulterstabilitat auf der einen und Schultermobilitat, d. h. Schulterfunktion, auf der anderen Seite sein. Unabhangig vom gewahlten Operationsverfahren suggeriert die aktuelle Literatur die Einhaltung folgender Leitlinien: anatomischer Operationszugang, Identifikation der der Instabilitat zugrunde liegenden verletzten Strukturen und anatomische Rekonstruktion derselbigen, fruhzeitige postoperative Nachbehandlung. Durch Einhaltung dieser Leitlinien scheint eine Optimierung der Ergebnisse nach operativer Behandlung bei traumatischer vorderer Schulterinstabilitat moglich.

Studies were performed to evaluate the effects of modeled microgravity on the induction of osteoblast apoptosis. MC3T3-E1 osteoblast-like cells were cultured in alginate carriers in the NASA-approved high aspect ratio vessel (HARV). This system subjects the cells to a time-averaged gravitational field (vector-averaged gravity) to simulate low gravity conditions. Cells were cultured in the HARV for five days, and then examined for apoptosis. In simulated microgravity, the cells remained vital, although analysis of expressed genes indicated that there was loss of the mature osteoblast phenotype. Additionally, we noted that there was a loss of the mitochondrial membrane potential, a low level of the antiapoptotic protein Bcl-2, as well as Akt protein, and the redox status of the cells was disturbed. All of these parameters indicated that vector-averaged gravity disrupts mitochondrial function, thereby sensitizing osteoblasts to apoptosis. We then used a challenge assay to evaluate the apoptotic sensitivity of the cells subjected to vector-averaged gravity. When challenged with staurosporine, cells subjected to vector-averaged gravity evidenced elevated levels of cell death relative to control cell populations. Another objective of the study was to improve upon conventional carriers by using alginate encapsulation to support cells in the HARV. We have demonstrated that the alginate carrier system affords a more robust system than surface-seeded carriers. This new system has the advantage of shielding cells from mechanical damage and fluid shear stresses on cells in the HARV, permitting carefully controlled studies of the effects of vector-averaged gravity.

TRAP, a characteristic marker of osteoclast differentiation, is an enzyme that plays an active role in the process of bone resorption. Despite the importance of TRAP in osteoclast biology, the components involved in the transcriptional regulation of this gene are largely unknown. This study investigated the regulation of TRAP transcription by the Myc oncoprotein in three different cell types. A series of nested TRAP promoter deletion constructs were cotransfected into P388D1 murine macrophages and C3H10T1/2 murine embryonic fibroblasts along with a backbone plasmid control or expression plasmids containing v-Myc, c-Myc, or an inactive v-Myc protein construct (delta84/NLS). Both v-Myc and c-Myc negatively regulated transcription from the TRAP promoter in P388D1 and C3H10T1/2 cells, 90% and 50%, respective to cell type and amount of endogenous Myc protein, and delta84/NLS had no effect. The functional Myc-responsive element(s) within the TRAP promoter was localized to a region between -436 and +1 bp, which contains two putative Myc-inhibitory binding sites coincident with an initiator element (Inr) at -116 bp and -18 bp. Conversely, in the HD-11EM chicken v-Myc transformed preosteoclast cell line, the full-length TRAP promoter transcription was increased when endogenous v-Myc levels were decreased in response to pretreatment of these cells with 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. This report provides the first evidence of the specific regulation of TRAP at the transcriptional level by Myc, a transcription factor that is normally expressed at relatively high levels in preosteoclasts and other myelomonocytic cells and suggests that Myc plays an active role in suppressing the transcription of a mature osteoclast selective gene.

Wear of orthopaedic implants generates particles capable of inducing bone resorption and aseptic loosening of the implant. The present study shows the combined effect of particles and cell activation on macrophage (THP-1) and osteoclast (HD-11EM) release of reactive oxygen and nitrogen species, providing insight into mechanisms that can lead to osteolysis. In the absence of cell activation, exposure of either cell type to submicron zirconia or latex particles did not elicit an increase in reactive oxygen and nitrogen species production. Suboptimal stimulation with 4 beta-phorbol-12-myristate-13-acetate (PMA) plus particles resulted in a synergistic release of superoxide (O2-), however, and a low-level production of nitric oxide small middle dot by THP-1 macrophages. Similarly, particle stimulation of tumor necrosis factor-alpha-activated THP-1 cells increased O2- release. Our findings show the synergistic effect of cell activation and wear particles on O2- production by activated macrophages and osteoclasts, suggesting O2- involvement in mediating osteolysis.

Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

Deep venous thrombosis is one of the most common perioperative complications after total hip arthroplasty. Systemic anticoagulation has been the gold standard for prophylaxis of postoperative deep venous thrombosis. There is no doubt that early mobilization and the use of pneumatic compression devices decrease the overall deep venous thrombosis rate. Single postoperative prophylaxis may decrease the overall deep venous thrombosis rate to 15-20% and the proximal deep venous thrombosis rate to approximately 7%. However,the activation of thrombogenesis is mainly an intraoperative event. The position of the extremity during the implantation of the femoral component leads to obstruction of the venous outflow. At the same time, the coagulation cascade is activated and markers of thrombogenesis in the blood are increased. By combining intraoperative (hypotensive epidural anesthesia and intraoperative heparin) and postoperative (pneumatic compression devices and aspirin) prophylaxis of deep venous thrombosis, the total deep venous thrombosis rate is reduced to less than 10% and the proximal deep venous thrombosis rate is reduced to 2%. Patients with increased risk for deep venous thrombosis should receive Coumadin or low-molecular weight heparin. In addition, hypotensive epidural anesthesia reduces the intraoperative blood loss and the need for postoperative blood transfusion.

Reactive oxygen species produced by activated neutrophils and monocytes are thought to be involved in mediating the loss of collagen and other matrix proteins at sites of inflammation. To evaluate their potential to oxidize the pyridinoline (Pyd) cross-links found in collagen types I and II, we reacted hydrogen peroxide (H2O2), hypochlorous acid/hypochlorite (HOCl/OCl−), and singlet oxygen (O2(1Δg)) with the Pyd substitutes, pyridoxamine dihydrochloride and vitamin B6, which share the same chemical structure and spectral properties of Pyd cross-links. Neither H2O2 (125–500 μm) nor O2(1Δg) (10–25 μm) significantly changed the spectral properties of pyridoxamine or vitamin B6. Reaction of HOCl/OCl− (12.5–50 μm) with pyridoxamine at pH 7.2 resulted in a concentration-dependent appearance of two new absorbance peaks and a decrease in fluorescence at 400 nm (excitation 325 nm). The new absorbance peaks correlated with the formation of anN-chloramine and the product of its subsequent reaction with pyridoxamine. In contrast, the extent to which HOCl reacted with vitamin B6, which lacks a primary amine group, was variable at this pH. At lysosomal pH 5.5, Cl2/HOCl/OCl− reacted with both pyridoxamine and vitamin B6. Four of the chlorinated products of this reaction were identified by gas chromatography-mass spectrometry and included 3-chloropyridinium, an aldehyde, and several chlorinated products with disrupted rings. To evaluate the effects of Cl2/HOCl/OCl− on Pyd cross-links in collagen, we exposed bone collagen type I and articular cartilage type II to HOCl. Treatment of either collagen type with HOCl at pH 5.0 or 7.2 resulted in the oxidation of amine groups and, for collagen type II, the specific decrease in Pyd cross-link fluorescence, suggesting that during inflammation both oxidations may be used by neutrophils and monocytes to promote the loss of matrix integrity.

Purpose: The purpose of this study was the evaluation of our results after posteroinferior capsular shift in patients with a posterior shoulder instability.

Despite the widespread implementation of highly cross-linked polyethylene (HXLPE) liners to reduce the clinical incidence of osteolysis, it is not known if the improved wear resistance will outweigh the inflammatory potential of HXLPE wear debris generated in vivo. Thus, we asked: What are the differences in size, shape, number, and biological activity of polyethylene wear particles obtained from primary total hip arthroplasty revision surgery of conventional polyethylene (CPE) versus remelted or annealed HXLPE liners? Pseudocapsular tissue samples were collected from revision surgery of CPE and HXLPE (annealed and remelted) liners, and digested using nitric acid. The isolated polyethylene wear particles were evaluated using scanning electron microscopy. Tissues from both HXLPE cohorts contained an increased percentage of submicron particles compared to the CPE cohort. However, the total number of particles was lower for both HXLPE cohorts, as a result there was no significant difference in the volume fraction distribution and specific biological activity (SBA; the relative biological activity per unit volume) between cohorts. In contrast, based on the decreased size and number of HXLPE wear debris there was a significant decrease in total particle volume (mm3/g of tissue). Accordingly, when the SBA was normalized by total particle volume (mm3/gm tissue) or by component wear volume rate (mm3/year), functional biological activity of the HXLPE wear debris was significantly decreased compared to the CPE cohort. Indications for this study are that the osteolytic potential of wear debris generated by HXLPE liners in vivo is significantly reduced by improvements in polyethylene wear resistance. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 467–475, 2013.

Sprengel deformity is a congenital malformation with usually unilateral elevation and medial rotation of the scapula. An omovertebral bone is generally present. Associated skeletal malformations are frequently present. Though functional impairment is mild, the cosmetic and psycho-social impairment can be considerable. The prognosis of early surgical therapy is good. The presented case also justifies surgical correction in the older child.

Intracellular reactive oxygen species (ROS) is a known activator of cell signaling, however too much ROS causes cell death. Our goal was to determine the optimal microsecond-pulsed Dielectric Barrier Discharge plasma (DBD-plasma) treatment dose (J/cm2) in which ROS/redox responses would potentially activate cell function but not cell death. In this study, we applied DBD-plasma to mesenchymal cells and evaluated intracellular ROS generation, redox, mitochondrial membrane potential and the Live/Dead response to increasing levels of DBD-plasma. Using fluorescent indicators to measure superoxide anion (O 2 −.) (MitoSOX™ Red), reduced glutathione (GSH) (ThiolTracker™ Violet) and mitochondrial membrane potential (ΔΨm) (MitoTracker® Red), we show that DBD-plasma doses of 1–5 J/cm2 stimulated an immediate (minutes) increase in O 2 − levels with a concomitant decrease in reduced thiol. The mitosox fluorescence intensity increased with DBD-plasma treatments until 1 J/cm2, after which levels plateaued regardless of increased dose. Reduced thiol fluorescent intensity showed an immediate 50% decrease regardless of DBD-plasma treatment dose. A 20% decrease in mitochondrial membrane potential occurred at 2 hrs post-DBD-plasma treatments 1 – 5 J/cm2, with significant cell death observed (fluorescent Live/Dead assay; syto- 13/propidium iodide) at levels of 2.5 J/cm2 and greater. Taken together, these results provide a range in which DBD (0–2.0 J/cm2) intracellular ROS generation and cellular redox change with little effect on cell viability. Understanding the optimal treatment levels DBD-plasma interactions is essential for developing DBD-plasma treatments to induce directed cell function such as; proliferation, differentiation and targeted gene expression.

Recent reports have suggested that production of superoxide or other reactive oxygen species by activated osteoclasts may play a role in the complex process of bone resorption; however, the enzyme responsible for production of superoxide by osteoclasts has not been characterized. To determine if osteoclasts express NADPH-oxidase, a superoxide-generating enzyme found in phagocytic leukocytes, immunohistochemical studies were performed on tibia from 1-5-d-old rats using mAbs 449 and 48 and an antiserum specific for p47-phox. These antibodies recognize epitopes on the alpha and beta subunits of cytochrome b558, respectively, and the p47 cytosolic component of NADPH-oxidase. We found that osteoclasts attached to bone surfaces in tibia expressed all three components, as did mature polymorphonuclear and some mononuclear leukocytes in the bone marrow. In many adherent osteoclasts, the cytochrome b558 subunits were localized to the ruffled-border and bone interfaces. Studies were also performed on mature rat tibia that had undergone controlled fracture. By two weeks the healing fractures develop a callus rich in actively resorbing osteoclasts. Osteoclasts within the calluses, and attached to bone surface, also expressed the cytochrome b558 proteins. In addition to demonstrating the expression of NADPH-oxidase, the active production of superoxide by osteoclasts was also demonstrated in situ in freshly isolated tibia using 3,3'-diaminobenzidine (DAB)-Mn2+, a histochemical method specific for superoxide localization. Osteoclasts attached to bone surfaces contained deposits of oxidized DAB which were observed by light microscopy. Nonstimulated polymorphonuclear and mononuclear leukocytes in the bone marrow did not contain DAB deposits unless stimulated with phorbol myristate acetate, a known activator of NADPH-oxidase. These findings indicate that osteoclasts contain NADPH-oxidase, and during the process of resorbing bone, are actively producing superoxide.

Open release of elbow stiffness via the lateral approach has proven to be a reliable option in the treatment of elbow stiffness over the last years. For evaluation of patient outcome after this procedure the current literature and studies were reviewed and analyzed with special reference to the increase in range of motion and patient satisfaction. It appears that particularly posttraumatic elbow stiffness with contracture of the capsule and minor alterations of the joint surface can achieve improvement in mobility and patient satisfaction. Therefore careful selection of patients is important for successful therapy.