One-Stage Revision of Infected Total Hip Arthroplasty with Bone Graft

There are many different opinions in the literature regarding the best procedure for revision of infected hip arthroplasty and hence in achieving long-term stabilization of a new implant. Thirty-two patients with 32 loose and infected total hip arthroplasties underwent revision with a bone graft in a 1-stage procedure. The bone graft was used in the acetabulum and femure in 25 patients, in the acetabulum alone in 4 patients and in the femur alone in 3 patients. A metal mesh was necessary in 15 patients to contain the morselized bone graft. At the time of surgical revision, 9 patients had a draining sinus, 6 had a closed sinus, and 17 had never had sinuses in the surgical wound. Antibiotic therapy was administered intravenously and orally for 6 months. Mean follow-up was 103 months (range, 63-183 months), and infection recurred in 2 (6.2%) cases. Further studies are necessary, and continuation of this method is justified.

Use of Allogeneic Bone Graft in Maxillary Reconstruction for Installation of Dental implants

The aim of this study is to evaluate the efficacy of the application of allogenous bone at the maxillo-mandibular reconstructions for future rehabilitation with dental implants. The patients were submitted to reconstruction of maxilla, using allogeneic bone grafts, in 3 different techniques: onlay grafts for lateral ridge augmentation, onlay and particulate bone for sinus lift grafting, and particulate alone for sinus lift grafts. Clinical and radiographic control was done at the postoperative phase for at least 8 months, until the patient could be submitted to the installation of dental implants. The results showed success in the majority of the cases, and dental implants could be installed. This can be considered an excellent alternative when compared with the use of autogenous grafts; because handling is easier, there is a great amount of material available and a possibility of using local anesthesia, and consequently there is a reduction of patient morbidity. (C) 2008 American Association of Oral and Maxillofacial Surgeons

Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED

Background Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting in multiple autoimmune phenomena including immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, and autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome. Conclusion Reviewing recent advances in our understanding of the small subgroup of PIDD patients with defined causes for autoimmunity may lead to the development of more effective treatment strategies for idiopathic human autoimmune diseases.

Neoskin development in the fetus with the use of a three-layer graft: an animal model for in utero closure of large skin defects

Objective: To assess the ability of a three-layer graft in the closuse of large fetal skin defects. Methods: Ovine fetuses underwent a large (4 x 3 cm) full-thickness skin defect over the lumbar region at 105 days` gestation (term = 140 days). A bilaminar artificial skin was placed over a cellulose interface to cover the defect (3-layer graft). The skin was partially reapproximated with a continuous nylon suture. Pregnancy was allowed to continue and the surgical site was submitted to histopathological analysis at different post-operative intervals. Results: Seven fetuses underwent surgery. One maternal/fetal death occurred, and the remaining 6 fetuses were analyzed. Artificial skin adherence to the wound edges was observed in cases that remained in utero for at least 15 days. Neoskin was present beneath the silicone layer of the bilaminar artificial skin. Conclusions: Our study shows that neoskin can develop in the fetus using a 3-layer graft, including epidermal growth beneath the silicone layer of the bilaminar skin graft. These findings suggest that the fetus is able to reepithelialise even large skin defects. Further experience is necessary to assess the quality of this repair.

Bovine Bone Screws: Metrology and Effects of Chemical Processing and Ethylene Oxide Sterilization on Bone Surface and Mechanical Properties

We assess the effects of chemical processing, ethylene oxide sterilization, and threading on bone surface and mechanical properties of bovine undecalcified bone screws. In addition, we evaluate the possibility of manufacturing bone screws with predefined dimensions. Scanning electronic microscopic images show that chemical processing and ethylene oxide treatment causes collagen fiber amalgamation on the bone surface. Processed screws hold higher ultimate loads under bending and torsion than the in natura bone group, with no change in pull-out strength between groups. Threading significantly reduces deformation and bone strength under torsion. Metrological data demonstrate the possibility of manufacturing bone screws with standardized dimensions.

Newly Formed Bone in Mandible Decortication Experimental Model Using rhBMP-2 Evaluated by Densitometric Study

The purpose of this study was to evaluate the newly formed bone, comparing two different carriers for rhBMP-2, using the decortication and nondecorticatication surgical technique in Wistar rat mandibles, evaluated by radiographic densitometry method. It was used fifty six animals according to specific treatment, which were sacrificed after 3 and 6 weeks after this. It was concluded that the decortication surgical technique was able to optimize the osteoinduction properties of the rhBMP-2, independently of the material carrier used and the period of time, according to radiographic densitometry technique.

Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short-term GH treatment on bone in adults with a mutation in the GHRH-receptor gene

Growth hormone (GH) influences bone mass maintenance. However, the consequences of lifetime isolated GH deficiency (IGHD) on bone are not well established. We assessed the bone status and the effect of 6 months of GH replacement in GH-naive adults with IGHD due to a homozygous mutation of the GH-releasing hormone (GHRH)-receptor gene (GHRHR). We studied 20 individuals (10 men) with IGHD at baseline, after 6 months of depot GH treatment, and 6 and 12 months after discontinuation of GH. Quantitative ultrasound (QUS) of the heel was performed and serum osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (ICTP) were measured. QUS was also performed at baseline and 12 months later in a group of 20 normal control individuals (CO), who did not receive GH treatment. At baseline, the IGHD group had a lower T-score on QUS than CO (-1.15 +/- 0.9 vs. -0.07 +/- 0.9, P < 0.001). GH treatment improved this parameter, with improvement persisting for 12 months post-treatment (T-score for IGHD = -0.59 +/- 0.9, P < 0.05). GH also caused an increase in serum OC (baseline vs. pGH, P < 0.001) and ICTP (baseline vs. pGH, P < 0.01). The increase in OC was more marked during treatment and its reduction was slower after GH discontinuation than in ICTP. These data suggest that lifetime severe IGHD is associated with significant reduction in QUS parameters, which are partially reversed by short-term depot GH treatment. The treatment induces a biochemical pattern of bone anabolism that persists for at least 6 months after treatment discontinuation.

Improved Endothelial Function and Reversal of Myocardial Perfusion Defects after Aerobic Physical Training in a Patient with Microvascular Myocardial Ischemia

The objective of this report is to document the effects of an aerobic training program on myocardial perfusion, and endothelial function abnormalities, and on the relief of angina in a patient with microvascular myocardial ischemia. A 53-year-old female patient exhibited precordial pain on effort and angiographically normal coronaries. Her symptoms had been present for 4 yrs despite pharmacologic treatment for the control of risk factors, with myocardial perfusion scintigraphy revealing an extensive reversible perfusion defect. She was submitted to aerobic training for 4 mos, obtaining significant improvement of the anginal symptoms. Additionally, after the aerobic training program, scintigraphy revealed the disappearance of the myocardial perfusion defect, with a marked improvement of endothelium-dependent vasodilatory response and an improved quality-of-life score. These results suggest that aerobic training can improve endothelial function, leading to a reduction of ischemia and an improved quality-of-life in patients with microvascular myocardial ischemia.

Bone Deposition, Bone Resorption, and Osteosarcoma

Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real-time PCR to evaluate the mRNA levels of the tartrate-resistant acid phosphatase (ACP5), colony stimulating factor-1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p = 0.041) and event free survival (p = 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p =0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1142-1148, 2010

Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats

Cannabidiol (CBD) is a cannabinoid component from Cannabis sativa that does not induce psychotomimetic effects and possess anti-inflammatory properties. In the present study we tested the effects of CBD in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying these effects. Periodontal disease was induced by a ligature placed around the mandible first molars of each animal. Male Wistar rats were divided into 3 groups: control animals; ligature-induced animals treated with vehicle and ligature-induced animals treated with CBD (5 mg/kg, daily). Thirty days after the induction of periodontal disease the animals were sacrificed and mandibles and gingival tissues removed for further analysis. Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-kappa B ligand RANKL/RANK. Moreover, gingival tissues from the CBD-treated group showed decreased neutrophil migration (MPO assay) associated with lower interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha production. These results indicate that CBD may be useful to control bone resorption during progression of experimental periodontitis in rats. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.

Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow

IL-13 and eotaxin play important, inter-related roles in asthma models. In the lungs, CysLT, produced by the 5-LO-LTC4S pathway, mediate some local responses to IL-13 and eotaxin; in bone marrow, CysLT enhance IL-5-dependent eosinophil differentiation. We examined the effects of IL-13 and eotaxin on eosinophil differentiation. Semi-solid or liquid cultures were established from murine bone marrow with GM-CSF or IL-5, respectively, and the effects of IL-13, eotaxin, or CysLT on eosinophil colony formation and on eosinophil differentiation in liquid culture were evaluated, in the absence or presence of: a) the 5-LO inhibitor zileuton, the FLAP inhibitor MK886, or the CysLT1R antagonists, montelukast and MK571; b) mutations that inactivate 5-LO, LTC4S, or CysLT1R; and c) neutralizing mAb against eotaxin and its CCR3 receptor. Both cytokines enhanced GM-CSF-dependent eosinophil colony formation and IL-5-stimulated eosinophil differentiation. Although IL-13 did not induce eotaxin production, its effects were abolished by anti-eotaxin and anti-CCR3 antibodies, suggesting up-regulation by IL-13 of responses to endogenous eotaxin. Anti-CCR3 blocked eotaxin completely. The effects of both cytokines were prevented by zileuton, MK886, montelukast, and MK571, as well as by inactivation of the genes coding for 5-LO, LTC4S, and CysLT1R. In the absence of either cytokine, these treatments or mutations had no effect. These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals. J. Leukoc. Biol. 87: 885-893; 2010.

Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice

The aim of this study was to unravel the mechanisms by which interleukin (IL)-10, a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6 wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk of age. Interleukin-10 KO mice presented significant alveolar bone loss when compared with WT mice, and this was not associated with changes in leukocyte counts or bacterial load. The levels of expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6, transforming growth factor-beta (TGF-beta), receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were similar between both strains, whereas a significant decrease of tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I collagen (COL-I) were expressed at similar levels in both strains, whereas the levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results demonstrate that the alveolar bone loss in the absence of IL-10 was associated with a reduced expression of osteoblast and osteocyte markers, an effect independent of microbial, inflammatory or bone-resorptive pathways.

PPAR-gamma agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis

Rosiglitazone (RGZ), an oral anti-hyperglycemic agent used for non-insulin-dependent diabetes mellitus, is a high-affinity synthetic agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Both in vitro and in vivo experiments have also revealed that RGZ possesses anti-inflammatory properties. Therefore, in the present study, we investigated the anti-inflammatory effects of RGZ in a rat model of periodontal disease induced by ligature placed around the mandible first molars of each animal. Male Wister rats were divided into four groups: 1) animals without ligature placement receiving administration of empty vehicle (control); 2) animals with ligature receiving administration of empty vehicle; 3) animals with ligature receiving administration with oral RGZ (10 mg/kg/day); and 4) animals with ligature receiving administration of subcutaneous RGZ (10 mg/kg/day). Thirty days after induction of periodontal disease, the animals were sacrificed, and mandibles and gingival tissues were removed for further analysis. An in vitro assay was also employed to test the inhibitory effects of RGZ on osteoclastogenesis. Histomorphological and immunohistochemical analyses of periodontal tissue demonstrated that RGZ-treated animals presented decreased bone resorption, along with reduced RANKL expression, compared to those animals with ligature, but treated with empty vehicle. Corresponding to such results obtained from in vivo experiments, RGZ also suppressed in vitro osteoclast differentiation in the presence of RANKL in MOCP-5 osteoclast precursor cells, along with the down-regulation of the expression of RANKL-induced TRAP mRNA. These data indicated that RGZ may suppress the bone resorption by inhibiting RANKL-mediated osteoclastogenesis elicited during the course of experimental periodontitis in rats. (C) 2009 Elsevier B.V. All rights reserved.

Cephalometric evaluation of facial pattern and hyoid bone position in children with obstructive sleep apnea syndrome

Objectives: To assess the development of face and hyoid bone in children with obstructive sleep apnea syndrome (OSAS) through lateral cephalometries. Materials and methods: Children aged 7-10 years with mixed dentition and with no previous otorhinolaryngologic, orthodontic or speech therapy treatments were studied. Twenty nasal breathers were compared to 20 mouth breathing children diagnosed as OSAS patients. All children underwent otorhinolaryngologic evaluation and cephalometries; children with OSAS also underwent nocturnal polysomnography in a sleep laboratory. Results: Children with OSAS presented increase in total and lower anterior heights of the face when compared to nasal breathers. In addition, children with OSAS presented a significantly more anterior and inferior position of the hyoid bone than nasal breathers. No significant differences in upper, anterior or posterior heights of the face were observed between groups. Conclusion: The results suggest that there are evident and early changes in facial growth and development among children with OSAS, characterized by increased total and inferior anterior heights of the face, as well as more anterior and inferior position of the hyoid bone. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

INTRAVITREAL INJECTION OF AUTOLOGOUS BONE MARROW-DERIVED MONONUCLEAR CELLS FOR HEREDITARY RETINAL DYSTROPHY A Phase I Trial

Purpose: To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods: A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 X 10(6) autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results: No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 mu V), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 mu V) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion: Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies. RETINA 31: 1207-1214, 2011