Cytotoxic effects of polycarbonate-based orthodontic brackets by activation of mitochondrial apoptotic mechanisms

OBJECTIVES: The aim of the study was to evaluate the biological effects of water eluents from polycarbonate based esthetic orthodontic brackets. METHODS: The composite polycarbonate brackets tested were Silkon Plus (SL, fiber-glass-reinforced), Elan ME (EL, ceramic particle-reinforced) and Elegance (EG, fiber-glass-reinforced). An unfilled polyoxymethylene bracket (Brilliant, BR) was used as control. The brackets' composition was analyzed by ATR-FTIR spectrometry. The cytotoxicity and estrogenicity of the eluents obtained after 3months storage of the brackets in water (37°C) were investigated in murine fibroblasts (NIH 3T3), breast (MCF-7) and cervical cancer (CCl-2/Hela) cell lines. RESULTS: SL and EG were based on aromatic-polycarbonate matrix, whereas EL consisted of an aromatic polycarbonate-polyethylene terepthalate copolymer. A significant induction of cell death and a concurrent decrease in cell proliferation was noted in the EG eluent-treated cells. Moreover, EG eluent significantly reduced the levels of the estrogen signaling associated gene pS2, specifically in MCF7 cells, suggesting that cell death induced by this material is associated with downregulation of estrogen signaling pathways. Even though oxidative stress mechanisms were equally activated by all eluents, the EG eluents induced expression of apoptosis inducing factor (AIF) and reduced Bcl-xL protein levels. SIGNIFICANCE: Some polycarbonate-based composite brackets when exposed to water release substances than activate mitochondrial apoptosis.

A Systematic Review of the Clinical Performance of Tooth-Retained and Implant-Retained Double Crown Prostheses with a Follow-Up of ≥3 Years

Purpose: The objective of this review was to systematically screen the literature for data related to the survival and complication rates observed with dental or implant double crown abutments and removable prostheses under functional loading for at least 3 years. Materials and Methods: A systematic review of the dental literature from January 1966 to December 2009 was performed in electronic databases (PubMed and Embase) as well as by an extensive hand search to investigate the clinical outcomes of double crown reconstructions. Results: From the total of 2412 titles retrieved from the search, 65 were selected for full-text review. Subsequently, 17 papers were included for data extraction. An estimation of the cumulative survival and complication rates was not feasible due to the lack of detailed information. Tooth survival rates for telescopic abutment teeth ranged from 82.5% to 96.5% after an observation period of 3.4 to 6 years, and for tooth-supported double crown retained dentures from 66.7% to 98.6% after an observation period of 6 to 10 years. The survival rates of implants were between 97.9% and 100% and for telescopic-retained removable dental prostheses with two mandibular implants, 100% after 3.0 and 10.4 years. The major biological complications affecting the tooth abutments were gingival inflammation, periodontal disease, and caries. The most frequent technical complications were loss of cementation and loss of facings. Conclusions: The main findings of this review are: (I) double crown tooth abutments and dentures demonstrated a wide range of survival rates. (II) Implant-supported mandibular overdentures demonstrated a favorable long-term prognosis. (III) A greater need for prosthetic maintenance is required for both tooth-supported and implant-supported reconstructions. (IV) Future areas of research would involve designing appropriate longitudinal studies for comparisons of survival and complication rates of different reconstruction designs.

Five-year results of a randomized controlled clinical trial comparing zirconia and titanium abutments supporting single-implant crowns in canine and posterior regions

OBJECTIVES: To test the survival rates, and the technical and biological complication rates of customized zirconia and titanium abutments 5 years after crown insertion. MATERIAL AND METHODS: Twenty-two patients with 40 single implants in maxillary and mandibular canine and posterior regions were included. The implant sites were randomly assigned to zirconia abutments supporting all-ceramic crowns or titanium abutments supporting metal-ceramic crowns. Clinical examinations were performed at baseline, and at 6, 12, 36 and 60 months of follow-up. The abutments and reconstructions were examined for technical and/or biological complications. Probing pocket depth (PPD), plaque control record (PCR) and Bleeding on Probing (BOP) were assessed at abutments (test) and analogous contralateral teeth (control). Radiographs of the implants revealed the bone level (BL) on mesial (mBL) and distal sides (dBL). Data were statistically analyzed with nonparametric mixed models provided by Brunner and Langer and STATA (P < 0.05). RESULTS: Eighteen patients with 18 zirconia and 10 titanium abutments were available at a mean follow-up of 5.6 years (range 4.5-6.3 years). No abutment fracture or loss of a reconstruction occurred. Hence, the survival rate was 100% for both. Survival of implants supporting zirconia abutments was 88.9% and 90% for implants supporting titanium abutments. Chipping of the veneering ceramic occurred at three metal-ceramic crowns supported by titanium abutments. No significant differences were found at the zirconia and titanium abutments for PPD (meanPPD(ZrO2) 3.3 ± 0.6 mm, mPPD(T) (i) 3.6 ± 1.1 mm), PCR (mPCR(Z) (rO) (2) 0.1 ± 0.3, mPCR(T) (i) 0.3 ± 0.2) and BOP (mBOP(Z) (rO) (2) 0.5 ± 0.3, mBOP(T) (i) 0.6 ± 0.3). Moreover, the BL was similar at implants supporting zirconia and titanium abutments (mBL(Z) (rO) (2) 1.8 ± 0.5, dBL(Z) (rO) (2) 2.0 ± 0.8; mBL(T) (i) 2.0 ± 0.8, dBL(T) (i) 1.9 ± 0.8). CONCLUSIONS: There were no statistically or clinically relevant differences between the 5-year survival rates, and the technical and biological complication rates of zirconia and titanium abutments in posterior regions.

Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development

Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database. 48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit.

Population-Based Design of Mandibular Plates Based on Bone Quality and Morphology

In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method enhances the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. Using computational anatomy techniques, the method automatically derives, from a set of computed tomography images, the mandibular angle and the bone thickness and intensity values at the path of every screw. An optimisation strategy is then used to optimise the two parameters of plate angle and screw position. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate. A statistically highly significant improvement was observed. Our experiments allowed us to conclude that an angle of 126° and a screw separation of 8mm is a more suitable design than the standard 120° and 9mm.

How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.

Tumor classification of six common cancer types based on proteomic profiling by MALDI imaging

In clinical diagnostics, it is of outmost importance to correctly identify the source of a metastatic tumor, especially if no apparent primary tumor is present. Tissue-based proteomics might allow correct tumor classification. As a result, we performed MALDI imaging to generate proteomic signatures for different tumors. These signatures were used to classify common cancer types. At first, a cohort comprised of tissue samples from six adenocarcinoma entities located at different organ sites (esophagus, breast, colon, liver, stomach, thyroid gland, n = 171) was classified using two algorithms for a training and test set. For the test set, Support Vector Machine and Random Forest yielded overall accuracies of 82.74 and 81.18%, respectively. Then, colon cancer liver metastasis samples (n = 19) were introduced into the classification. The liver metastasis samples could be discriminated with high accuracy from primary tumors of colon cancer and hepatocellular carcinoma. Additionally, colon cancer liver metastasis samples could be successfully classified by using colon cancer primary tumor samples for the training of the classifier. These findings demonstrate that MALDI imaging-derived proteomic classifiers can discriminate between different tumor types at different organ sites and in the same site.

Biologically based strategies to augment rotator cuff tears

Lesions of the rotator cuff (RC) are among the most frequent tendon injuries. In spite of the developments in both open and arthroscopic surgery, RC repair still very often fails. In order to reduce the failure rate after surgery, several experimental in vitro and in vivo therapy methods have been developed for biological improvement of the reinsertion. This article provides an overview of the current evidence for augmentation of RC reconstruction with growth factors. Furthermore, potential future therapeutic approaches are discussed. We performed a comprehensive search of the PubMed database using various combinations of the keywords "tendon," "rotator cuff," "augmentation," "growth factor," "platelet-rich fibrin," and "platelet-rich plasma" for publications up to 2011. Given the linguistic capabilities of the research team, we considered publications in English, German, French, and Spanish. We excluded literature reviews, case reports, and letters to the editor.

Intraoperative template-molded bone flap reconstruction for patient-specific cranioplasty

Cranioplasty is a common neurosurgical procedure. Free-hand molding of polymethyl methacrylate (PMMA) cement into complex three-dimensional shapes is often time-consuming and may result in disappointing cosmetic outcomes. Computer-assisted patient-specific implants address these disadvantages but are associated with long production times and high costs. In this study, we evaluated the clinical, radiological, and cosmetic outcomes of a time-saving and inexpensive intraoperative method to mold custom-made implants for immediate single-stage or delayed cranioplasty. Data were collected from patients in whom cranioplasty became necessary after removal of bone flaps affected by intracranial infection, tumor invasion, or trauma. A PMMA replica was cast between a negative form of the patient's own bone flap and the original bone flap with exactly the same shape, thickness, and dimensions. Clinical and radiological follow-up was performed 2 months post-surgery. Patient satisfaction (Odom criteria) and cosmesis (visual analogue scale for cosmesis) were evaluated 1 to 3 years after cranioplasty. Twenty-seven patients underwent intraoperative template-molded patient-specific cranioplasty with PMMA. The indications for cranioplasty included bone flap infection (56%, n = 15), calvarian tumor resection (37%, n = 10), and defect after trauma (7%, n = 2). The mean duration of the molding procedure was 19 ± 7 min. Excellent radiological implant alignment was achieved in 94% of the cases. All (n = 23) but one patient rated the cosmetic outcome (mean 1.4 years after cranioplasty) as excellent (70%, n = 16) or good (26%, n = 6). Intraoperative cast-molded reconstructive cranioplasty is a feasible, accurate, fast, and cost-efficient technique that results in excellent cosmetic outcomes, even with large and complex skull defects.

Population-based design of mandibular fixation plates with bone quality and morphology considerations

In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method may enhance the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The computational method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. The method automatically derives the mandibular angle and the bone thickness and intensity values at the path of every screw from a set of computed tomography images. An optimization strategy is then used to optimize the two parameters of plate angle and screw position. The method was applied to two populations of different genders. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate (MODUS(®) TriLock(®) 2.0/2.3/2.5, Medartis AG, Basel, Switzerland). The proposed designs resulted in a statistically significant improvement in the available bone thickness when compared to the standard plate. There is a higher probability that the proposed implants cover areas of thicker cortical bone without compromising the bone mineral density around the screws. The obtained results allowed us to conclude that an angle and screw separation of 129° and 9 mm for females and 121° and 10 mm for males are more suitable designs than the commercially available 120° and 9 mm.

Three-dimensional surface reconstruction within noncontact diffuse optical tomography using structured light

A main field in biomedical optics research is diffuse optical tomography, where intensity variations of the transmitted light traversing through tissue are detected. Mathematical models and reconstruction algorithms based on finite element methods and Monte Carlo simulations describe the light transport inside the tissue and determine differences in absorption and scattering coefficients. Precise knowledge of the sample's surface shape and orientation is required to provide boundary conditions for these techniques. We propose an integrated method based on structured light three-dimensional (3-D) scanning that provides detailed surface information of the object, which is usable for volume mesh creation and allows the normalization of the intensity dispersion between surface and camera. The experimental setup is complemented by polarization difference imaging to avoid overlaying byproducts caused by inter-reflections and multiple scattering in semitransparent tissue.

Incorporation of a preexisting scar in the star-flap technique for nipple reconstruction

This report describes the authors' currently favored method of nipple reconstruction in cases of a pre-existing scar on the breast mound that passes through the intended site of nipple reconstruction.

Inhibition of the AKT/mTOR and erbB pathways by gefitinib, perifosine and analogs of gonadotropin-releasing hormone I and II to overcome tamoxifen resistance in breast cancer cells

Endocrine resistance in breast cancer remains a major clinical problem and is caused by crosstalk mechanisms of growth factor receptor cascades, such as the erbB and PI3K/AKT pathways. The possibilities a single breast cancer cell has to achieve resistance are manifold. We developed a model of 4-hydroxy-tamoxifen (OHT)‑resistant human breast cancer cell lines and compared their different expression patterns, activation of growth factor receptor pathways and compared cells by genomic hybridization (CGH). We also tested a panel of selective inhibitors of the erbB and AKT/mTOR pathways to overcome OHT resistance. OHT‑resistant MCF-7-TR and T47D-TR cells showed increased expression of HER2 and activation of AKT. T47D-TR cells showed EGFR expression and activated MAPK (ERK-1/2), whereas in resistant MCF-7-TR cells activated AKT was due to loss of CTMP expression. CGH analyses revealed remarkable aberrations in resistant sublines, which were predominantly depletions. Gefitinib inhibited erbB signalling and restored OHT sensitivity in T47D-TR cells. The AKT inhibitor perifosine restored OHT sensitivity in MCF-7-TR cells. All cell lines showed expression of receptors for gonadotropin-releasing hormone (GnRH) I and II, and analogs of GnRH-I/II restored OHT sensitivity in both resistant cell lines by inhibition of erbB and AKT signalling. In conclusion, mechanisms to escape endocrine treatment in breast cancer share similarities in expression profiling but are based on substantially different genetic aberrations. Evaluation of activated mediators of growth factor receptor cascades is helpful to predict response to specific inhibitors. Expression of GnRH-I/II receptors provides multi-targeting treatment strategies.

Changes in the volume and density of calvarial split bone grafts after alveolar ridge augmentation

OBJECTIVES: One main problem occurring after bone grafting is resorption, leading to insufficient bone volume and quality, and may subsequently cause dental implant failure. Comparison of graft volume and bone density of iliac crest and calvarial transplants determined by animal studies demonstrates significantly lower resorption of bone grafts harvested from the skull. This paper is the first clinical study evaluating bone volume and density changes of calvarial split bone grafts after alveolar ridge reconstruction. MATERIAL AND METHODS: Bone volume and density were determined using CT scans and the software program Dicom Works in a total of 51 calvarial grafts after alveolar ridge augmentation in 15 patients. CT scans were taken in all 15 patients immediately after grafting (T0) and before implantation after a postoperative period of 6 months (T1). In five patients (26 calvarial grafts), a 1-year follow-up was performed (T2). RESULTS: A mean volume reduction of 16.2% at T1 (15 patients) and 19.2% at T2 (five patients) was observed. Bone density was high--about 1000 Hounsfield units--and did not change during the 1-year period. At the time of implantation, 41 transplants were classified as quality 1 bone and 10 as quality 2-3 bone. Grafting area and the technique used for grafting (inlay or onlay graft) did not affect the postoperative bone volume reduction. Generalized osteoporosis did not increase the resorption rate of calvarial transplants. CONCLUSION: Based on these findings, calvarial split bone grafts are a promising alternative for alveolar ridge reconstruction in dental implantology.

Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95

PURPOSE: To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor-negative or stage III tumor with five or more positive axillary nodes. PATIENTS AND METHODS: Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). RESULTS: After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor-positive tumors benefited significantly from DI-EC. CONCLUSION: There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.