Marker-Based Method for Analyzing the Three-Dimensional Upper Body Kinematics of Violinists: Reproducibility.

BACKGROUND: Recently, Wolf et al. proposed a novel, marker-based method to analyze the three-dimensional upper-body kinematics of high string players for clinical application. The method provides an objective evaluation of high string players' motor strategies, especially in the shoulder complex, by distinguishing between the scapulothoracic (ST) and glenohumeral (GH) joints, while minimizing skin movement artifacts, marker occlusions, and limitations due to instrument placement. Nevertheless, reproducibility of kinematic measurements is crucial for clinical applications. The aim of this study was to assess the method's reproducibility in terms of reliability and repeatability. METHODS: One healthy professional violinist underwent a total of nine bowing trials in three different laboratory sessions. Each trial was conducted by one of two different examiners. A biomechanical model was applied to motion capture data of the pelvis, thorax, spine, and head, as well as both upper limbs (consisting of the scapula, upper arm, forearm and hand). Reproducibility was assessed by calculating inter- and intra-tester, inter-session, and intra-subject measurement errors for each rotational degree of freedom in the upper-body segments and joints. FINDINGS: Small measurement errors were accepted to be good indicators for reproducibility. Intra- and inter-tester errors were found to be small (< 3° for the most part). Both inter-session and intra-subject repeatability were found to be larger (< 5° for the most part). INTERPRETATION: This study generally showed the novel, marker-based method to have good reproducibility for a healthy violinist. This indicates that the proposed method is a reliable tool for quantifying upper-body movements during violin playing across subjects, examiners, laboratories, and motion capture systems.

H3F3A-mutated giant cell tumour of bone without giant cells-clinical presentation, radiology and histology of three cases.

AIMS: Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS: Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. CONCLUSIONS: We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.

Marker-Based Method for Analyzing the Three-Dimensional Upper Body Kinematics of Violinists and Violists: Development and Clinical Feasibility.

AIMS: High string players (violin and viola) often suffer from musculoskeletal disorders. Although 3D motion analysis has proved helpful in diagnosing different musculoskeletal syndromes and identifying injurious movement patterns in violin and viola performance, more detailed analyses of upper body movement strategies and especially of the shoulder complex have not yet been recorded. The use of spherical surface markers on some anatomical landmarks is, however, inappropriate when an instrument is being played. The aim of this study was to develop and evaluate a novel marker-based method for analyzing upper body kinematics of high string players using conditions specific to violin and viola playing. METHODS: A custom upper body marker set was developed and a biomechanical model applied to 3D motion capture data of the pelvis, thorax, spine, head, and both upper limbs (scapula, upper arm, forearm, hand) of 12 professional violinists, to assess its clinical feasibility. FINDINGS: Lumbar and thoracic spine, thorax, neck, and left upper limb were quite static, while extensive motion occurred in the right upper limb. Most rotation angles showed a reasonable intersubject variability except for glenohumeral and wrist joints. Significant differences were observed between G- and D-string bowing, especially in the left wrist and right shoulder joints. INTERPRETATION: This study suggests that the proposed method is a valid tool for quantifying upper body movements in violin and viola performance. With the extended upper body model, it will improve understanding of the motor strategies adopted by high string players and may contribute to injury prevention, diagnosis, and treatment.

Oxidative stress and NO generation in the rat pancreatitis induced by pancreatic duct ligation.

The interaction between nitric oxide (NO) and superoxides is critical in the development of an acute pancreatitis. Previously, we reported that the expression of superoxides and of the NO-generating enzyme (NO synthase, NOS) was up-regulated in the human pancreatitis, especially within the exocrine compartment indicating an exceptional susceptibility of the exocrine parenchyma to oxidative stress. The aim of the present study was to compare the regulation of NO signalling pathways in the human pancreatitis and in an animal model of an acute pancreatitis induced by pancreatic duct ligation (PDL) in rats. In the PDL-induced rat pancreatitis, we revealed a similar pattern of oxidative stress and NOS up-regulation in acinar and in ductal compartments, like in the human pancreatitis. This demonstrates that the PDL-induced rat pancreatitis is a proper model for further studies of acute pancreatitis development in humans.

Radiation-Induced Intraspinal Chondrosarcoma: A Case Report.

Study Design Case report and review of the literature. Objective To report a unique case of an intraspinal chondrosarcoma that was diagnosed 18 years after radiotherapy for a cervical carcinoma and its remarkably unusual clinical presentation. Methods A retrospective case description of an intraspinal mass lesion that occurred 6 weeks after previous spinal surgery. Results Within ∼9 weeks, the tumor had infiltrated the peritoneal cavity and reached the lumbar subcutaneous tissue. Conclusion Radiation-induced sarcomas are rare, are highly aggressive, and may be difficult to diagnose. Furthermore, the only means of achieving long-term survival is through early and extensive surgery.

Signal amplification in immunohistochemistry: loose-jointed deformable heteropolymeric HRP conjugates vs. linear polymer backbone HRP conjugates.

Improvements in reagents and protocols for immunohistochemistry have led to increased sensitivity of detection systems. A significant level of signal amplification was achieved by the chain-polymer conjugate technology utilizing enzyme-labeled inert "backbone" molecule of dextran (Dako). However, the relatively large size of the dextran molecule in aqueous phase appears to create spatial hindrance compromising the penetrative ability of the detection reagent. Novel AmpliStain™ detection systems (SDT GmbH, Baesweiler, Germany) seem to overcome these constraints offering a more compact and deformable conjugate design that facilitates agile penetration through the narrowest diffusion pathways in tissue sections. Here, we compared the level of signal amplification achievable with AmpliStain™-HRP (SDT) and EnVision™+-HRP (Dako). Our results show that the AmpliStain™-HRP systems allow higher dilutions of primary antibodies in both immunohistochemistry and ELISA. Compared with EnVision™+, anti-mouse AmpliStain™ enables at least three times more sensitive detection of mouse antibodies, whereas anti-rabbit AmpliStain™ is ten times more sensitive than anti-rabbit EnVision™+.

Alterations in the tumor suppressor gene p16(INK4A) are associated with aggressive behavior of penile carcinomas.

Alterations in the p16/cyclinD1/Rb and ARF/Mdm2/p53 pathways are frequent events in the pathogenesis of squamous cell carcinomas. Different mechanisms of p16 regulation have been described for penile carcinomas so far. Therefore, expression of p16 and p53 was immunohistochemically detected with monoclonal antibodies in 52 primary invasive penile squamous cell carcinomas. The carcinomas were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for mutations in the p16(INK4A) and the p53 gene. In addition, we examined the promoter status of p16(INK4A) by methylation-specific PCR. The presence of human papilloma virus (HPV) 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Data were compared to clinical data. Concerning p16, 26 (50%) tumors showed positive immunohistochemistry, 32 (62%) tumors showed allelic loss and 22 tumors (42%) showed promoter hypermethylation. All tumors with negative p16 immunohistochemistry showed LOH near the p16(INK4A) locus and/or hypermethylation of the p16(INK4A) promoter. HPV 16 DNA was detected in 17 tumors, ten of them with positive p16 immunostaining. The remaining seven tumors with negative p16 staining showed allelic loss and/or promoter hypermethylation. Evidence of lymph node metastasis was significantly associated with negative p16 immunohistochemistry as well as with combined LOH and promoter hypermethylation (p = 0.003 and p = 0.018, respectively). Allelic loss around p53 was found in 22 tumors (42%), and seven mutations of the p53 gene could be demonstrated in our tumors. No correlations could be found between any p53 alteration and clinical parameters.

Effects of a dexamethasone-releasing stent on osteoneogenesis in a rabbit model.

BACKGROUND: This study is an evaluation of wound healing in an animal model for surgery of frontal sinusitis and treatment effect of topically released dexamethasone using a drug-releasing stent with special emphasis of osteoneogenesis. METHODS: A prospective, controlled, randomized, double-blinded animal study was performed. Nineteen New Zealand white rabbits were subjected to surgery via an external approach, a 4-mm circular wound was created on the medial side of the maxillary sinus and the underlying bone was denuded of periosteum. The wound was covered in a randomized fashion with either a silicone foil or a new dexamethasone-releasing stent system. Twelve to 30 days later, the animals were killed and a histological examination was performed. RESULTS: In comparison with the baseline bony thickness (40 micrometer) obtained in one animal, osteoneogenesis occurred on both paranasal sides but was significantly less if a dexamethasone-releasing stent was applied (117 [95% CI, 116-128]; 52 [95% CI, 43-64]; p < 0.001). Maximal bony thickness was observed in both treatment groups between days 20 and 25 with a tendency toward a higher percentage decrease in the dexamethasone-treated sides (p < 0.08). Using a visual analog scale (0-5) a significantly smoother bony surface was observed for dexamethasone (2 [95% CI, 1.1-1.9]; 2 [95% CI, 1.8-2.2]; p < 0.01). CONCLUSION: Using a new drug-releasing stent system, dexamethasone efficiently decreases postoperative osteoneogenesis in a standardized animal wound model for endoscopic sinus surgery. Therefore, the use of this system may be of value to decrease restenosis rates using corticosteroids in selected patients after frontal sinus surgery, especially the endoscopic modified Lothrop procedure.

Effects of topically applied dexamethasone on mucosal wound healing using a drug-releasing stent.

OBJECTIVE/HYPOTHESIS: Evaluation of the impact of continuously topically released dexamethasone using a drug-releasing stent on quality of regenerated mucosa after full thickness injury in the paranasal sinuses. STUDY DESIGN: Prospective, controlled, randomized, double-blinded animal study. METHODS: Nineteen New Zealand white rabbits were subjected to surgery: via an external approach, a 4 mm circular wound was created on the medial side of the maxillary sinus. The wound was covered in a randomized fashion with either a silicone foil or a new drug releasing stent system. Twelve to 30 days later, the animals were killed and histology and electron microscopy were performed. One animal was used for baseline comparisons at day 0. RESULTS: No animals were lost due to infection or dislocation of the stent, leaving 18 animals for evaluation of postoperative healing quality. According to macroscopic examination, extent of granulations was smaller in the treatment group (dexamethasone: median 0 [95% confidence interval: 0.1-0.6]) than the silicone group (2 [1.5-2.3]; P < or = .05). Epithelial wound healing was complete in all specimens, whereas the stroma was significantly thinner in the dexamethasone-group (44 [37-60]; 178 [148-214]). Improved healing quality was achieved significantly more often on the treatment, than on the control side. Scanning electron microscopy revealed no difference between both groups. CONCLUSIONS: Using a new drug-releasing stent system, dexamethasone efficiently decreases granulation formation and stroma thickness without impeding epithelial differentiation. Therefore, the use of this system may be of value to decrease restenosis rates in selected patients after frontal sinus surgery.

Loss of heterozygosity occurs predominantly, but not exclusively, in the epithelial compartment of pleomorphic adenoma.

Pleomorphic adenoma (PA), being the most common benign tumor of the salivary glands, is composed of epithelial and mesenchymal compartments. In this study, we analyzed 19 microsatellite markers from chromosomal arms 6q, 8q, 9p, 12q, and 17p in 31 PAs and 3 carcinoma ex pleomorphic adenomas (CXPAs) as well as 11 other non-PA-related carcinomas of the salivary gland for comparison. In our analysis, we differentiated between epithelial and mesenchymal tissues. Loss of heterozygosity (LOH) in PAs was most often found in 8q (32%) and 12q (29%). Two of the three CXPAs displayed allelic loss at all chromosomal arms investigated, whereas the results of the non-PA-related carcinomas were rather heterogeneous. LOH could not only be detected in the epithelial, but also in the mesenchymal, compartments of a subset of PAs, especially at chromosomal arm 8q. Concerning the CXPAs, we were able to demonstrate allelic losses not only in the malignant epithelial compartment, but also in the residual adenoma parts. Our data give further evidence that alterations in 8q may be an early event in PA tumorigenesis, whereas LOH in 12q may characterize cells with the potential to transform in CXPAs.

Histomorphometric evaluation of the influence of the diabetic metabolic state on bone defect healing depending on the defect size in spontaneously diabetic BB/OK rats.

Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and impair bone repair in both humans and animals. The objective of this study was the detailed histomorphometric evaluation of the influence of the diabetic metabolic state on bone formation and remodeling during bone defect healing depending on the defect size in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to IDDM in man. Based on blood-glucose values at the time of surgery, postoperative blood-glucose course, and postoperative insulin requirements, 80 spontaneously diabetic BB/OK rats were divided into groups with well-compensated or poorly compensated metabolic state. Forty LEW.1A rats served as normoglycemic controls. Using a Kirschner wire, bone defects of different sizes were created proximal to the knee joint space in both femora. Ten animals from each group were killed on postoperative days 7, 14, 24, and 42, and specimens were processed undecalcified for quantitative bone histomorphometry. In terms of bone histomorphometry, our study did not show any differences in bone defect healing between the groups where the defect size was 0.4 mm. Larger bone defects (0.8 mm) only showed significant differences in the structural calculations after the 24th postoperative day exclusively in poorly compensated diabetic rats compared to well-compensated diabetic and control rats (P < 0.05 or P < 0.01). In bone defect sizes more than 1.2 mm, severe mineralization disorders occurred within the first 14 days exclusively in rats with poorly compensated diabetic metabolic state with a highly significant (P < 0.001) or significant (P < 0.01) decrease of all fluorochrome-based parameters of mineralization, apposition, formation, and timing of mineralization in comparison to spontaneously diabetic rats with well-compensated diabetic metabolic state and control rats. These results demonstrate that the bone repair of minor bone defects (0.4 mm) is independent of the diabetic metabolic state in spontaneously diabetic BB/OK rats. In larger bone defects (more than 0.8 mm), the bone defect healing in spontaneously diabetic BB/OK rats is impaired exclusively in poorly compensated diabetic metabolic states. This study suggests that strictly controlled insulin treatment resulting in a well-compensated diabetic metabolic state will ameliorate the impaired histomorphometric parameters of IDDM bone defect healing.

A new resorbable bone void filler in trauma: early clinical experience and histologic evaluation.

Six patients with traumatic bone injuries were treated by packing ultraporous beta-tricalcium phosphate (beta-TCP), a synthetic bone void filler, into defect sites using firm finger pressure. Radiographs showed new bone consolidating in treated sites after as little as 2 months. A biopsy obtained from a fractured calcaneus 9 months after surgery showed new bone growing within the ultraporous scaffold. Regions of newly mineralized bone and woven bone in the scaffold suggested that the defect site was undergoing repair. Some new bone had developed lamellar architecture. Higher radiodensity and slower resorption of ultraporous bone void filler in this human case, relative to that seen in a canine study, is attributed to slower metabolism in humans relative to dogs and to greater packing pressures used in the clinic. The histology specimen did not indicate untoward inflammatory response or significant foreign body reaction. Thus, this first human histology report supports the use of biocompatible ultraporous beta-TCP to enhance new bone formation in bone defects.