Post-treatment glenoid classification system for total shoulder arthroplasty.

PubMed

Churchill, R Sean

2012-04-01

Over the past 10 years, numerous advancements in glenoid preparation and resurfacing have occurred. Current glenoid classification systems are either focused solely on the patient's preoperative glenoid bone configuration or on the available glenoid bone stock in revision arthroplasty cases. While these systems provide value in preoperative planning, they fail to properly classify the surgical reconstruction completed. A literature review of common bone preparation methods and sources of glenoid prosthetic failure was performed. Based upon this review, a classification system for grading the status of the glenoid after prosthetic implantation was developed. A 6 category, post-treatment, glenoid classification system is proposed: type 0: no reaming; type I: glenoid reaming into but not through the subchondral bone; type II: glenoid reaming which perforates through <50% of the subchondral bone surface area; type III: glenoid reaming which perforates through >50% of the subchondral bone surface area; type IV: use of structural bone graft; and type V: use of a posterior augmented glenoid prosthesis. Types I-III are further subdivided into subtype A which have 100% bone support of the prosthesis, and subtype B which have a region of unsupported prosthesis. The classification system proposed addresses the surgical management of the glenoid during prosthetic replacement. This unique approach to classifying the glenoid following surgical intervention will allow direct follow-up comparison of similarly treated glenoid replacements. Future multicenter studies, possibly through joint registry databases, could then determine the long-term efficacy of the various glenoid preparation methods. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities.

PubMed

Möhlhenrich, S C; Abouridouane, M; Heussen, N; Hölzle, F; Klocke, F; Modabber, A

2016-11-01

The aim of this study was to investigate the influence of bone density and drilling protocol on heat generation during implant bed preparation. Ten single and 10 gradual implant sites with diameters of 2.8, 3.5, and 4.2mm were prepared in four artificial bone blocks (density types I-IV; D1-D4). Drilling was done at constant speed (1500rpm) and with external irrigation (50ml/min); vertical speed was set at 2mm/s. An infrared camera was used for temperature measurements. Significantly higher temperatures for single drilling were found between 2.8-mm drills in D1 (P=0.0014) and D4 (P<0.0001) and between 3.5-mm drills in D3 (P=0.0087) and D4 (P<0.0001), as well as between 4.2-mm drills in D1 (P<0.0001) and D4 (P=0.0014). Low bone density led to a thermal decrease after single drilling and a thermal increase after gradual drilling. Burs with a large diameter always showed a higher temperature generation. In comparisons between 2.8- and 4.2-mm diameters for both single and gradual drills, significant differences (P<0.001) were noted for bone types II, III, and IV. Single drilling could generate more heat than traditional sequential drilling, and bone density, as well as drill diameter, influenced thermal increases. Particularly in lower-density bone, conventional sequential drilling seems to raise the temperature less. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review.

PubMed

Magoulas, Pilar L; El-Hattab, Ayman W; Roy, Angshumoy; Bali, Deeksha S; Finegold, Milton J; Craigen, William J

2012-06-01

Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4-alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of secondary alveolar bone grafting outcomes performed after canine eruption in complete unilateral cleft lip and palate.

PubMed

Lorenzoni, Diego Coelho; Janson, Guilherme; Bastos, Juliana Cunha; Carvalho, Roberta Martinelli; Bastos, José Carlos; de Cássia Moura Carvalho Lauris, Rita; Henriques, José Fernando Castanha; Ozawa, Terumi Okada

2017-01-01

Evaluate the results of secondary alveolar bone grafting (SABG) in patients with complete unilateral cleft lip and palate (UCLP), operated after permanent canine eruption (CE). Seventy-four periapical radiographs from patients with complete UCLP (mean age 14 years) submitted to SABG were retrospectively analyzed for the amount of bone in the cleft site through the Bergland and Chelsea scales. Of the cases, 47.3 % was classified as Bergland type I and Chelsea type A, 35.2 % as type II/C, 6.7 % as type III/D, and 10.8 % as type IV/failure. When the canine was moved into the grafted area, the success rate (type I/A) was 56.8 %; for cases in which the space was maintained for an implant or prosthetic finishing, the index was 45.8 %; however, this difference was not statistically significant. Even in advanced ages, after permanent canine eruption, SABG can be considered a highly successful procedure. This research shows good results of secondary alveolar bone grafting performed in patients with unilateral complete cleft lip and palate, even when it was performed after eruption of the permanent canine in the cleft area.

Failure mechanisms and closed reduction of a constrained tripolar acetabular liner.

PubMed

Robertson, William J; Mattern, Christopher J; Hur, John; Su, Edwin P; Pellicci, Paul M

2009-02-01

Unlike traditional bipolar constrained liners, the Osteonics Omnifit constrained acetabular insert is a tripolar device, consisting of an inner bipolar bearing articulating within an outer, true liner. Every reported failure of the Omnifit tripolar implant has been by failure at the shell-bone interface (Type I failure), failure at the shell-liner interface (Type II failure), or failure of the locking mechanism resulting in dislocation of the bipolar-liner interface (Type III failure). In this report we present two cases of failure of the Omnifit tripolar at the bipolar-femoral head interface. To our knowledge, these are the first reported cases of failure at the bipolar-femoral head interface (Type IV failure). In addition, we described the first successful closed reduction of a Type IV failure.

Paget's disease of bone resembling bone metastasis from gastric cancer.

PubMed

Shimoyama, Yasuyuki; Kusano, Motoyasu; Shimoda, Yoko; Ishihara, Shingo; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Sano, Takaaki; Hirato, Junko; Mori, Masatomo

2011-08-01

A 74-year-old man had an endoscopic type 0'-IIc tumor in the upper gastric body on the greater curvature and biopsy showed the tumor to be a well-differentiated adenocarcinoma (Group 5). He was referred to us for endoscopic submucosal dissection (ESD). Endoscopy revealed fold convergency, fold swelling, and fusion of the fold, indicating tumor invasion into the submucosa, which was outside the indications for ESD. In addition, there was an increase of serum bone-type alkaline phosphatase (ALP-III and ALP-IV) and urinary cross-linked N-terminal telopeptide of type I collagen (a bone metabolism marker), while (18)F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left pelvis and Th10, suggesting bone metastases. We first diagnosed gastric cancer with bone metastases; however, the symptoms suggested pathological bone fracture and no bone pain. Therefore, a computed tomography-guided aspiration bone biopsy was performed to exclude the possibility of Paget's disease of bone. Biopsy specimens revealed no tumor and a mosaic pattern. No increased uptake of (18)F-FAMT (L-[3-(18)F] α-methyltyrosine) supported a diagnosis of no bone metastases from gastric cancer. We finally diagnosed gastric cancer accompanied by Paget's disease of bone and performed a laparoscopy-assisted proximal gastrectomy. The pathological diagnosis was U less 0-IIb, and U post 0-IIc ypT1a (M) N0H0P0M0 yp stage IA. In gastric cancer patients with suspected bone metastasis, we also need to consider Paget's disease of bone.

Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

PubMed

Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2014-10-01

The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. © 2014 American Society for Bone and Mineral Research.

Suppression of the motor deficit in a mucolipidosis type IV mouse model by bone marrow transplantation

PubMed Central

Walker, Marquis T.; Montell, Craig

2016-01-01

Mucolipidosis IV (MLIV) is a severe lysosomal storage disorder, which results from loss of the TRPML1 channel. MLIV causes multiple impairments in young children, including severe motor deficits. Currently, there is no effective treatment. Using a Drosophila MLIV model, we showed previously that introduction of trpml+ in phagocytic glia rescued the locomotor deficit by removing early dying neurons, thereby preventing amplification of neuronal death from cytotoxicity. Because microglia, which are phagocytic cells in the mammalian brain, are bone marrow derived, and cross the blood–brain barrier, we used a mouse MLIV model to test the efficacy of bone marrow transplantation (BMT). We found that BMT suppressed the reduced myelination and the increased caspase-3 activity due to loss of TRPML1. Using a rotarod test, we demonstrated that early BMT greatly delayed the motor impairment in the mutant mice. These data offer the possibility that BMT might provide the first therapy for MLIV. PMID:27270598

Reconstruction with 3D-printed pelvic endoprostheses after resection of a pelvic tumour.

PubMed

Liang, H; Ji, T; Zhang, Y; Wang, Y; Guo, W

2017-02-01

The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction. A total of 35 patients underwent resection of a pelvic tumour and reconstruction using 3D-printed endoprostheses between September 2013 and December 2015. According to Enneking's classification of bone defects, there were three Type I lesions, 12 Type II+III lesions, five Type I+II lesions, two Type I+II+III lesions, ten type I+II+IV lesions and three type I+II+III+IV lesions. A total of three patients underwent reconstruction using an iliac prosthesis, 12 using a standard hemipelvic prosthesis and 20 using a screw-rod connected hemipelvic prosthesis. All patients had an en bloc resection. Margins were wide in 15 patients, marginal in 14 and intralesional in six. After a mean follow-up of 20.5 months (6 to 30), 25 patients survived without evidence of disease, five were alive with disease and five had died from metastatic disease. Complications included seven patients with delayed wound healing and two with a dislocation of the hip. None had a deep infection. For the 30 surviving patients, the mean Musculoskeletal Society 93 score was 22.7 (20 to 25) for patients with an iliac prosthesis, 19.8 (15 to 26) for those with a standard prosthesis, and 17.7 (9 to 25) for those with a screw-rod connected prosthesis. The application of 3D-printing technology can facilitate the precise matching and osseointegration between implants and the host bone. We found that the use of 3D-printed pelvic prostheses for reconstruction of the bony defect after resection of a pelvic tumour was safe, without additional complications, and gave good short-term functional results. Cite this article: Bone Joint J 2017;99-B:267-75. ©2017 The British Editorial Society of Bone & Joint Surgery.

Targeting the LRP5 pathway improves bone properties in a mouse model of Osteogenesis Imperfecta

PubMed Central

Jacobsen, Christina M.; Barber, Lauren A.; Ayturk, Ugur M.; Roberts, Heather J.; Deal, Lauren E.; Schwartz, Marissa A.; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G.; Warman, Matthew L.

2014-01-01

The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5p.A214V) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis Imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5+/p.A214V mice to Col1a2+/p.G610C mice, which model human type IV OI. We found that Col1a2+/p.G610C;Lrp5+/p.A214V offspring had significantly increased bone mass and strength compared to Col1a2+/p.G610C;Lrp5+/+ littermates. The improved bone properties were not due to altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2+/p.G610C mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody treated mice had significantly increased bone mass and strength compared to vehicle treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. PMID:24677211

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

PubMed Central

Yao, Wei; Evan Lay, Yu-An; Kot, Alexander; Liu, Ruiwu; Zhang, Hongliang; Chen, Haiyan; Lam, Kit; Lane, Nancy E.

2017-01-01

Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. PMID:27334693

Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-06-20

Dedifferentiated Liposarcoma; Gastrointestinal Stromal Tumor; Metastatic Liposarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Pleomorphic Liposarcoma; Stage III Bone Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Bone Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Bone Sarcoma AJCC v7; Stage IVB Bone Sarcoma AJCC v7; Unresectable Liposarcoma

Reconstruction of Long Bone Infections Using the Induced Membrane Technique: Tips and Tricks.

PubMed

Mauffrey, Cyril; Hake, Mark E; Chadayammuri, Vivek; Masquelet, Alain-Charles

2016-06-01

The management of posttraumatic long bone osteomyelitis remains a challenging clinical problem. A systematic approach is necessary, beginning with eradication of the infected bone and soft tissue. There are a number of options for reconstruction of the remaining bone defect, including the induced membrane technique developed by Masquelet. We describe our technique for the 2-stage treatment of long bone osteomyelitis. The first stage involves a radical debridement, stabilization of the bone with either external fixation or an antibiotic-coated intramedullary nail, and placement of a polymethylmethacrylate spacer. The second stage includes excision of the spacer and placement of autologous bone graft. Various resection methods, fixation strategies, antibiotic additives, and types of bone grafts or substitutes can be used. The purpose of our technical article is to share our personal experience and describe several nuances that are critical for the success of this treatment strategy. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate.

PubMed

Lindahl, K; Kindmark, A; Rubin, C-J; Malmgren, B; Grigelioniene, G; Söderhäll, S; Ljunggren, Ö; Åström, E

2016-06-01

Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe OI; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated. COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n=33, type III n=25 and type IV n=21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non-vertebral and vertebral fractures were collected prior to, and at several time points during treatment. An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to Δ LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p<0.0003, <0.0001 and 0.0003 for all OI types I, III and IV respectively). The reduced fracture rate was maintained for types I and IV, while an additional decrease was observed over time for type III. The fracture rate was reduced also in individuals with continued low BMD after >4yrs Pamidronate. Twice as many boys as girls with OI type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p=0.0236). Greater Δ LS BMD, but smaller Δ fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11years of age at treatment initiation (p<0.0001). Pamidronate treatment in children with all types of OI increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type. Copyright © 2016 Elsevier Inc. All rights reserved.

Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment

NASA Astrophysics Data System (ADS)

Lloyd, William R.; Sinder, Benjamin P.; Salemi, Joseph; Ominsky, Michael S.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

2015-02-01

Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (Scl- Ab), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v1, carbonate v1, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment.

Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury

PubMed Central

Sarasúa, J González; López, S Pérez; Viejo, M Álvarez; Basterrechea, M Pérez; Rodríguez, A Fernández; Gutiérrez, A Ferrero; Gala, J García; Menéndez, Y Menéndez; Augusto, D Escudero; Arias, A Pérez; Hernández, J Otero

2011-01-01

Context Pressure ulcers are especially difficult to treat in patients with spinal cord injury (SCI) and recurrence rates are high. Prompted by encouraging results obtained using bone marrow stem cells to treat several diseases including chronic wounds, this study examines the use of autologous stem cells from bone marrow to promote the healing of pressure ulcers in patients with SCI. Objective To obtain preliminary data on the use of bone marrow mononuclear cells (BM-MNCs) to treat pressure ulcers in terms of clinical outcome, procedure safety, and treatment time. Participants Twenty-two patients with SCI (19 men, 3 women; mean age 56.41 years) with single type IV pressure ulcers of more than 4 months duration. Interventions By minimally invasive surgery, the ulcers were debrided and treated with BM-MNCs obtained by Ficoll density gradient separation of autologous bone marrow aspirates drawn from the iliac crest. Results In 19 patients (86.36%), the pressure ulcers treated with BM-MNCs had fully healed after a mean time of 21 days. The number of MNCs isolated was patient dependent, although similar clinical outcomes were observed in each case. Compared to conventional surgical treatment, mean intra-hospital stay was reduced from 85.16 to 43.06 days. Following treatment, 5 minutes of daily wound care was required per patient compared to 20 minutes for conventional surgery. During a mean follow-up of 19 months, none of the resolved ulcers recurred. Conclusions Our data indicate that cell therapy using autologous BM-MNCs could be an option to treat type IV pressure ulcers in patients with SCI, avoiding major surgical intervention. PMID:21756569

Finite element analysis of maxillary bone stress caused by Aramany Class IV obturator prostheses.

PubMed

Miyashita, Elcio Ricardo; Mattos, Beatriz Silva Câmara; Noritomi, Pedro Yoshito; Navarro, Hamilton

2012-05-01

The retention of an Aramany Class IV removable partial dental prosthesis can be compromised by a lack of support. The biomechanics of this obturator prosthesis result in an unusual stress distribution on the residual maxillary bone. This study evaluated the biomechanics of an Aramany Class IV obturator prosthesis with finite element analysis and a digital 3-dimensional (3-D) model developed from a computed tomography scan; bone stress was evaluated according to the load placed on the prosthesis. A 3-D model of an Aramany Class IV maxillary resection and prosthesis was constructed. This model was used to develop a finite element mesh. A 120 N load was applied to the occlusal and incisal platforms corresponding to the prosthetic teeth. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis were expressed in MPa. Under posterior load, tensile and compressive stresses were observed; the tensile stress was greater than the compressive stress, regardless of the bone region, and the greatest compressive stress was observed on the anterior palate near the midline. Under an anterior load, tensile stress was observed in all of the evaluated bone regions; the tensile stress was greater than the compressive stress, regardless of the bone region. The Aramany Class IV obturator prosthesis tended to rotate toward the surgical resection when subjected to posterior or anterior loads. The amount of tensile and compressive stress caused by the Aramany Class IV obturator prosthesis did not exceed the physiological limits of the maxillary bone tissue. (J Prosthet Dent 2012;107:336-342). Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy.

PubMed

De Cock, E; Hutton, J; Canney, P; Body, J J; Barrett-Lee, P; Neary, M P; Lewis, G

2005-12-01

Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.

Influence of Drilling Speed on Stability of Tapered Dental Implants: An Ex Vivo Experimental Study.

PubMed

Almeida, Karen P; Delgado-Ruiz, Rafael; Carneiro, Leandro G; Leiva, Alberto Bordonaba; Calvo-Guirado, Jose Luis; Gómez-Moreno, Gerardo; Malmström, Hans; Romanos, Georgios E

2016-01-01

The aim of this study was to evaluate whether the drilling speed used during implant site preparation influences primary stability. Eighty tapered designed implants (3.8 × 10 mm) were inserted following osteotomies created in solid rigid polyurethane foam (simulating bone type II) and cellular rigid polyurethane foam (simulating bone type IV). Half were prepared using drilling speeds of 800 rpm (low speed), and the other half were prepared using speeds of 1,500 rpm (high speed). Following insertion, implant primary stability was measured using Periotest and Osstell (resonance frequency analysis [RFA]) devices. Two-way analysis of variance (ANOVA) used for this study found that the drilling speed used to create the osteotomies appeared to have no significant impact on primary stability. The bone quality and not the osteotomy drilling speed seems to influence the implant primary stability.

Temperature and time variations during osteotomies performed with different piezosurgical devices: an in vitro study.

PubMed

Delgado-Ruiz, R A; Sacks, D; Palermo, A; Calvo-Guirado, J L; Perez-Albacete, C; Romanos, G E

2016-09-01

The aim of this experimental in vitro study was to evaluate the effects of the piezoelectric device in temperature and time variations in standardized osteotomies performed with similar tip inserts in bovine bone blocks. Two different piezosurgical devices were used the OE-F15(®) (Osada Inc., Los Angeles, California, USA) and the Surgybone(®) (Silfradent Inc., Sofia, Forli Cesena, Italy). Serrated inserts with similar geometry were coupled with each device (ST94 insert/test A and P0700 insert/test B). Osteotomies 10 mm long and 3 mm deep were performed in bone blocks resembling type II (dense) and type IV (soft) bone densities with and without irrigation. Thermal changes and time variations were recorded. The effects of bone density, irrigation, and device on temperature changes and time necessary to accomplish the osteotomies were analyzed. Thermal analysis showed significant higher temperatures during piezosurgery osteotomies in hard bone without irrigation (P < 0.05). The type of piezosurgical device did not influence thermal variations (P > 0.05). Time analysis showed that the mean time values necessary to perform osteotomies were shorter in soft bone than in dense bone (P < 0.05). Within the limitations of this in vitro study, it may be concluded that the temperature increases more in piezosurgery osteotomies in dense bone without irrigation; the time to perform the osteotomy with piezosurgery is shorter in soft bone compared to hard bone; and the piezosurgical device have a minimal influence in the temperature and time variations when a similar tip design is used during piezosurgery osteotomies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Engraftment of donor mesenchymal stem cells in chimeric BXSB includes vascular endothelial cells and hepatocytes.

PubMed

Jones, Olcay Y; Gok, Faysal; Rushing, Elisabeth J; Horkayne-Szakaly, Iren; Ahmed, Atif A

2011-01-01

Somatic tissue engraftment was studied in BXSB mice treated with mesenchymal stem cell transplantation. Hosts were conditioned with nonlethal radiation prior to introducing donor cells from major histocompatibility complex-matched green fluorescent protein transgenic mice. Transplant protocols differed for route of injection, ie, intravenous (i.v.) versus intraperitoneal (i.p.), and source of mesenchymal stem cells, ie, unfractionated bone marrow cells, ex vivo expanded mesenchymal stem cells, or bone chips. Tissue chimerism was determined after short (10-12 weeks) or long (62 weeks) posttransplant follow-up by immunohistochemistry for green fluorescent protein. Engraftment of endothelial cells was seen in several organs including liver sinusoidal cells in i.v. treated mice with ex vivo expanded mesenchymal stem cells or with unfractionated bone marrow cells. Periportal engraftment of liver hepatocytes, but not engraftment of endothelial cells, was found in mice injected i.p. with bone chips. Engraftment of adipocytes was a common denominator in both i.v. and i.p. routes and occurred during early phases post-transplant. Disease control was more robust in mice that received both i.v. bone marrow and i.p. bone chips compared to mice that received i.v. bone marrow alone. Thus, the data support potential use of mesenchymal stem cell transplant for treatment of severe lupus. Future studies are needed to optimize transplant conditions and tailor protocols that may in part be guided by fat and endothelial biomarkers. Furthermore, the role of liver chimerism in disease control and the nature of cellular communication among donor hematopoietic and mesenchymal stem cells in a chimeric host merit further investigation.

Slow drilling speeds for single-drill implant bed preparation. Experimental in vitro study.

PubMed

Delgado-Ruiz, R A; Velasco Ortega, E; Romanos, G E; Gerhke, S; Newen, I; Calvo-Guirado, J L

2018-01-01

To evaluate the real-time bone temperature changes during the preparation of the implant bed with a single-drill protocol with different drill designs and different slow drilling speeds in artificial type IV bone. For this experimental in vitro study, 600 implant bed preparations were performed in 10 bovine bone disks using three test slow drilling speeds (50/150/300 rpm) and a control drilling speed (1200 rpm). The temperature at crestal and apical areas and time variations produced during drilling with three different drill designs with similar diameter and length but different geometry were recorded with real-life thermographic analysis. Statistical analysis was performed by two-way analysis of variance. Multiple comparisons of temperatures and time with the different drill designs and speeds were performed with the Tukey's test. T Max values for the control drilling speed with all the drill designs (D1 + 1200; D2 + 1200; D3 + 1200) were higher compared to those for the controls for 11 ± 1.32 °C (p < 0.05). The comparison of T Max within the test groups showed that drilling at 50 rpm resulted in the lowest temperature increment (22.11 ± 0.8 °C) compared to the other slow drilling speeds of 150 (24.752 ± 1.1 °C) and 300 rpm (25.977 ± 1.2 °C) (p < 0.042). Temperature behavior at crestal and apical areas was similar being lower for slow drilling speeds compared to that for the control drilling speed. Slow drilling speeds required significantly more time to finish the preparation of the implant bed shown as follows: 50 rpm > 150 rpm > 300 rpm > control (p < 0.05). A single-drill protocol with slow drilling speeds (50, 150, and 300 rpm) without irrigation in type IV bone increases the temperature at the coronal and apical levels but is below the critical threshold of 47 °C. The drill design in single-drill protocols using slow speeds (50, 150, and 300 rpm) does not have an influence on the thermal variations. The time to accomplish the implant bed preparation with a single-drill protocol in type IV bone is influenced by the drilling speed and not by the drill design. As the speed decreases, then more time is required.

Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

NASA Astrophysics Data System (ADS)

Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

2004-07-01

Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

PubMed

Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

2003-01-01

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

[Descriptive study of activity of the bone marrow donor registry and bank from the Murcia Region (southeast of Spain) (1994-2004)].

PubMed

Rojas Montero, G M; Alvarez López, M R; López Bermejo, A; Moya Quiles, M R; Muro Amador, M

2006-11-01

To perform a descriptive study of the activity of the Bank of marrow donors from Murcia Region. All donors in the Bank of bone marrow from 1994 until 2004 (n=3137). This study analysed the number of donors, their origin and, performed donor searches activity. Donors were typed by serological microlymphocytotoxicity and molecular PCR-SSO and PCR-SSP techniques. The Bank of bone marrow has 3,137 voluntary donors typed in low- and high-resolution. A total of 680 donor searches have been realized. The origin of the donors according to several Areas of Health in which the Autonomous Community of Murcia is divided, is the following one: Area I (28%), Area II (18 %), Area III (23 %), Area IV (6 %), Area VI (10 %) and other provinces (12%). An increase is observed in the number of annual donors as well as an increase very marked of donor searches that are realized every year, especially in 2004.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

PubMed

Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

2015-02-01

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases.

PubMed

Henk, Henry J; Kaura, Satyin; Teitelbaum, April

2012-01-01

For patients with bone metastases, skeletal-related events including fracture are common, can cause considerable morbidity, and may reduce overall survival (OS). This retrospective analysis assessed the effect of Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), on fracture risk and OS in patients with bone metastases from lung cancer (LC). (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.) A claims-based analysis using commercial and Medicare Advantage data from >45 US managed-care plans was used to evaluate the association between fracture risk and treatment persistency (31-90, 91-180, 181-365, and ≥366 days) and follow-up duration in LC patients diagnosed with bone metastases between 01/01/2001 and 12/31/2006 and treated with ZOL or without (no IV-BP). Persistency was defined as the absence of a >45-day gap between ZOL treatments. Analysis of variance tests were used to compare follow-up duration, a proxy for OS, between ZOL persistency groups. The effect of time to treatment with ZOL was also assessed. In 9874 LC patients with bone metastases (n = 1090 ZOL; n = 8784 no IV-BP) the unadjusted relative fracture risk was reduced by 40% with ZOL vs no IV-BP; fracture risk decreased consistently with increasing duration of ZOL treatment. Even short-term (31-90 days) ZOL significantly reduced fracture risk (47%) vs no IV-BP (p = 0.005) with adjustment for differences in demographic and clinical characteristics. Delaying ZOL until after bone metastases were diagnosed significantly increased fracture risk (p = 0.0017). For a sub-set of patients included in a survival analysis (n = 550 ZOL; n = 4512 no IV-BP), mortality was significantly lower (mean, 38.6 vs 46.8 deaths/100 person-years; p = 0.038) in those treated with ZOL vs no IV-BP. Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited clinical information and the ability to control for prognostic factors. This retrospective analysis demonstrates that LC patients with bone metastases receiving ZOL had significantly reduced risk of fracture (p = 0.005) and death (p < 0.038) vs patients receiving no IV-BP. Longer ZOL persistency consistently yielded better outcomes, with ≥12 months' treatment producing the greatest benefit.

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

ClinicalTrials.gov

2017-05-12

Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma

Effects of mechanical repetitive load on bone quality around implants in rat maxillae

PubMed Central

Uto, Yusuke; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept “bone quality”, which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones. PMID:29244883

Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

PubMed

Uto, Yusuke; Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones.

Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells.

PubMed

Li, Q S; Meng, F Y; Zhao, Y H; Jin, C L; Tian, J; Yi, X J

2017-08-01

This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p. Plasma miR-214-5p was highly expressed in patients with bone fracture compared with HCs after fracture (p < 0.05 or p < 0.01). Inhibition of miR-214-5p increased the viability of MC3T3-E1 cells and the expressions of COL1A1 and COL-X, but decreased the apoptotic rate and COL-II expression (p < 0.05 or p < 0.01). COL4A1 was a target of miR-214-5p, and was negatively regulated by miR-214-5p (p < 0.05 or p < 0.01). Overexpression of COL4A1 showed a similar impact on cell viability, apoptotic rate, and COL1A1, COL-II, and COL-X expressions inhibiting miR-214-5p (p < 0.01). Inhibition of miR-214-5p promotes cell survival and extracellular matrix (ECM) formation of osteoblastic MC3T3-E1 cells by targeting COL4A1. Cite this article: Q. S. Li, F. Y. Meng, Y. H. Zhao, C. L. Jin, J. Tian, X. J. Yi. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells. Bone Joint Res 2017;6:464-471. DOI: 10.1302/2046-3758.68.BJR-2016-0208.R2. © 2017 Yi et al.

Effectiveness of recombinant human bone morphogenetic protein-7 in the management of congenital pseudoarthrosis of the tibia: a randomised controlled trial.

PubMed

Das, Sakti Prasad; Ganesh, Shankar; Pradhan, Sudhakar; Singh, Deepak; Mohanty, Ram Narayan

2014-09-01

Despite the popularity and an increased use of bone morphogenetic protein to improve bone healing in patients with congenital pseudoarthrosis of the tibia (CPT), no previous study has compared its efficacy against any other procedure. We randomised 20 consecutive patients (mean age 4.1 years) with CPT (Crawford type IV) associated with neurofibromatosis type 1(NF1) and no previous history of surgery into two groups. Group 1 received recombinant human bone morphogenetic protein-7 (rhBMP-7) along with intramedullary Kirschner (K)-wire fixation and autologous bone grafting; group 2 received only K wire and grafting. Outcome measures were time to achieve union, Johnston grade, tibial length and the American Orthopaedic Foot and Ankle Society (AOFAS) score, which were evaluated preoperatively and at five year follow-up. Study results showed that patients in group 1 achieved primary bone union at a mean of 14.5 months [standard error (SE) 5.2], whereas group 2 took a mean of 17.11 months (SE 5.0). However, the log-rank test showed no difference in healing times between groups at all time points (P = 0.636). There was a statistically significant pre- to post operative improvement (P < 0.05) within groups for the other outcome measures. In a five year follow-up, these results suggest that rh-BMP-7 and autologous bone grafting is no better than autologous grafting alone.

Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity.

PubMed

Lavrador, Catarina; Mascarenhas, Ramiro; Coelho, Paulo; Brites, Cláudia; Pereira, Alfredo; Gogolewski, Sylwester

2016-03-01

Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control-untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P < 0.05) although the comparison between these groups was not possible. The results obtained in this study suggest that biodegradable polyurethane substitutes modified with biologically active substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting.

Bone age in cerebral palsy

PubMed Central

Miranda, Eduardo Régis de Alencar Bona; Palmieri, Maurício D'arc; de Assumpção, Rodrigo Montezuma César; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patrícia Maria de Moraes Barros

2013-01-01

Objective To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status. Methods 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle. Results In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54). Conclusion There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series. PMID:24453693

A Cross-sectional Multicenter Study of Osteogenesis Imperfecta in North America – Results from the Linked Clinical Research Centers

PubMed Central

Patel, Ronak M; Nagamani, Sandesh CS; Cuthbertson, David; Campeau, Philippe M; Krischer, Jeffrey P; Shapiro, Jay R; Steiner, Robert D; Smith, Peter A; Bober, Michael B; Byers, Peter H; Pepin, Melanie; Durigova, Michaela; Glorieux, Francis H; Rauch, Frank; Lee, Brendan H; Smith, Tracy; Sutton, V. Reid

2017-01-01

Osteogenesis Imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n=544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean LS aBMD was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answer questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of “phenotypic expansion” driven by next-generation sequencing. PMID:24754836

Levels of Evidence in Orthopaedic Trauma Literature.

PubMed

Scheschuk, Joseph P; Mostello, Andrew J; Lombardi, Nicholas J; Maltenfort, Mitchell G; Freedman, Kevin B; Tjoumakaris, Fotios P

2016-07-01

To review and critically assess trends observed regarding the levels of evidence in published articles in orthopaedic traumatology literature. The Journal of Orthopaedic Trauma, Journal of Bone and Joint Surgery-American, and Clinical Orthopaedics and Related Research. All articles from the years 1998, 2003, 2008, and 2013 in The Journal of Orthopaedic Trauma (JOT) and orthopaedic trauma-related articles from The Journal of Bone and Joint Surgery-American (JBJS-A) and Clinical Orthopaedics and Related Research (CORR) were analyzed. Articles were categorized by type and ranked for level of evidence according to guidelines from the Centre for Evidence-Based Medicine. Study type and standardized level of evidence were determined for each article. Articles were subcategorized as high-level evidence (I, II), moderate-level evidence (III), and low-level evidence (IV, V). During the study period, Journal of Bone and Joint Surgery-American reduced its low-level studies from 80% to 40% (P = 0.00015), Clinical Orthopaedics and Related Research decreased its low-level studies from 70% to 27%, and Journal of Orthopaedic Trauma decreased its low-level studies from 78% to 45%. Level IV and V therapeutic, prognostic, and diagnostic studies demonstrated significant decreases during the study period (P = 0.0046, P < 0.0001, P = 0.026). The percentage of high-level studies increased from 13% to 19%; however, this was not significant (P = 0.42). There was a trend showing an increase in level I and II studies for therapeutic, prognostic, and diagnostic studies (P = 0.06). There has been a statistically significant decrease in lower level of evidence studies published in the orthopaedic traumatology literature over the past 15 years.

[Application of rafting K-wire technique for tibial plateau fractures].

PubMed

Zhang, Xing-zhou; Yu, Wei-zhong; Li, Yun-feng; Liu, Yan-hui

2015-12-01

To summarize application of rafting K-wires technique for tibial plateau fractures. From January 2013 to January 2015,45 patients with tibial plateau fractures were treated by locking plate with rafting K-wires, including 33 males and 12 females with an average of 44.2 years old ranging from 22 to 56 years old. According to Schatzker classification, 6 cases were type II, 8 were type Ill, 4 were type IV, 4 were type V, and 5 were type VI. Allogeneic bone graft were performed for bone defects. All patients were fixed with two to five K-wires. Part of weight loading were encouraged at 3 months after operation,and full weight-loading were done at 5 months after operation. Postoperative complications were observed,and Rasmussen clinical and radiological assessment were used to evaluate clinical results. All Patients were followed up from 10 to 23 months with average of 14 months. According to Rasmussen clinical and radiological assessment, clinical scores 23.58 ± 6.33, radiological scores were 14.00 ± 6.33; and excellent and good rates were 82.2% and 77.8% respectively. Four patients occurred severe osteoporosis and collapse of articular surface; 5 patients occurred traumatic arthritis. Rafting K-wires technique with anatomized armor plate could effective fix and support platform collapse and joint bone fragments, increase support surface area and reduce postoperative reduction loss rate.

Assessment of zoledronic acid treatment patterns and clinical outcomes in patients with bone metastases from genitourinary cancers.

PubMed

Henk, Henry J; Kaura, Satyin

2012-01-01

Patients with bone metastases secondary to genitourinary (GU) cancer are at risk for skeletal-related events (SREs), including bone pain requiring palliative radiotherapy, fractures or surgery to bone, spinal cord compression, and hypercalcemia of malignancy. These SREs can be debilitating and potentially life-limiting. This study examined treatment practices and the association of treatment patterns with Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), with SREs and fractures. (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.) Retrospective analysis of commercial and Medicare Advantage enrollment and medical claims data was performed to evaluate IV-BP use and SRE patterns in adult patients with GU cancers. Criteria included diagnosis of ≥1 bone metastasis and prostate cancer (PC), renal cell carcinoma (RCC), or bladder cancer (BlC) between January 2001 and December 2006; continuous healthcare plan enrollment for ≥6 months before the index date; and no evidence of prior IV-BP use. Patients were followed until disenrollment from the healthcare plan or December 2007. Of 6347 patients (PC, n = 4976; RCC, n = 941; BlC, n = 430; mean [standard deviation] age: 68.9 [11.1] years), only approximately 23% received ZOL. The mean time between diagnosis of bone metastasis and ZOL initiation was approximately 108 days. Among patients with PC, fracture risk was significantly smaller for ZOL vs no IV-BP (incidence rate ratio = 0.70; p < 0.001), and 2-year survival was significantly longer for ZOL-treated vs no IV-BP patients (p = 0.007). Patients with longer persistency on ZOL had a smaller fracture risk than patients with shorter persistency. Sub-set analyses were not performed for RCC and BIC because the proportion of patients treated was too low. Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited and accurate available information, and unavailable information including clinical or disease-specific parameters. Intravenous BP therapy is not always received in patients with bone metastases secondary to GU cancers, and, when used, there are typically long time periods before treatment initiation. Without IV-BPs, PC patients have significantly larger risks of fracture and death compared with ZOL-treated patients, and benefits appear to be larger with increasing persistency on ZOL.

Wrapping grafting for congenital pseudarthrosis of the tibia

PubMed Central

Yan, An; Mei, Hai-Bo; Liu, Kun; Wu, Jiang-Yan; Tang, Jin; Zhu, Guang-Hui; Ye, Wei-Hua

2017-01-01

Abstract Objective: Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. Methods: We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. Results: In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. Conclusion: Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia. PMID:29310362

Outcomes of implants and restorations placed in general dental practices: a retrospective study by the Practitioners Engaged in Applied Research and Learning (PEARL) Network.

PubMed

Da Silva, John D; Kazimiroff, Julie; Papas, Athena; Curro, Frederick A; Thompson, Van P; Vena, Donald A; Wu, Hongyu; Collie, Damon; Craig, Ronald G

2014-07-01

The authors conducted a study to determine the types, outcomes, risk factors and esthetic assessment of implants and their restorations placed in the general practices of a practice-based research network. All patients who visited network practices three to five years previously and underwent placement of an implant and restoration within the practice were invited to enroll. Practitioner-investigators (P-Is) recorded the status of the implant and restoration, characteristics of the implant site and restoration, presence of peri-implant pathology and an esthetic assessment by the P-I and patient. The P-Is classified implants as failures if the original implant was missing or had been replaced, the implant was mobile or elicited pain on percussion, there was overt clinical or radiographic evidence of pathology or excessive bone loss (> 0.2 millimeter per year after an initial bone loss of 2 mm). They classified restorations as failures if they had been replaced or if there was abutment or restoration fracture. The authors enrolled 922 implants and patients from 87 practices, with a mean (standard deviation) follow-up of 4.2 (0.6) years. Of the 920 implants for which complete data records were available, 64 (7.0 percent) were classified as failures when excessive bone loss was excluded from the analysis. When excessive bone loss was included, 172 implants (18.7 percent) were classified as failures. According to the results of univariate analysis, a history of severe periodontitis, sites with preexisting inflammation or type IV bone, cases of immediate implant placement and placement in the incisor or canine region were associated with implant failure. According to the results of multivariate analysis, sites with preexisting inflammation (odds ratio [OR] = 2.17; 95 percent confidence interval [CI], 1.41-3.34]) or type IV bone (OR = 1.99; 95 percent CI, 1.12-3.55) were associated with a greater risk of implant failure. Of the 908 surviving implants, 20 (2.2 percent) had restorations replaced or judged as needing to be replaced. The majority of P-Is and patients were satisfied with the esthetic outcomes for both the implant and restoration. These results suggest that implant survival and success rates in general dental practices may be lower than those reported in studies conducted in academic or specialty settings. The results of this study, generated in the private general practice setting, add to the evidence base to facilitate implant treatment planning.

Bone alterations are associated with ankle osteoarthritis joint pain

PubMed Central

Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

2016-01-01

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain. PMID:26776564

Bone alterations are associated with ankle osteoarthritis joint pain.

PubMed

Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

2016-01-18

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain.

Augmentation of tibial plateau fractures with an injectable bone substitute: CERAMENT™. Three year follow-up from a prospective study.

PubMed

Iundusi, Riccardo; Gasbarra, Elena; D'Arienzo, Michele; Piccioli, Andrea; Tarantino, Umberto

2015-05-13

Reduction of tibial plateau fractures and maintain a level of well aligned congruent joint is key to a satisfactory clinical outcome and is important for the return to pre-trauma level of activity. Stable internal fixation support early mobility and weight bearing. The augmentation with bone graft substitute is often required to support the fixation to mantain reduction. For these reasons there has been development of novel bone graft substitutes for trauma applications and in particular synthetic materials based on calcium phosphates and/or apatite combined with calcium sulfates. Injectable bone substitutes can optimize the filling of irregular bone defects. The purpose of this study was to assess the potential of a novel injectable bone substitute CERAMENT™|BONE VOID FILLER in supporting the initial reduction and preserving alignment of the joint surface until fracture healing. From June 2010 through May 2011 adult patients presenting with acute, closed and unstable tibial plateau fractures which required both grafting and internal fixation, were included in a prospective study with percutaneous or open reduction and internal fixation (ORIF) augmented with an injectable ceramic biphasic bone substitute CERAMENT™|BONE VOID FILLER (BONESUPPORT™, Lund, Sweden) to fill residual voids. Clinical follow up was performed at 1, 3, 9 and 12 months and any subsequent year; including radiographic analysis and Rasmussen system for knee functional grading. Twenty four patients, balanced male-to-female, with a mean age of 47 years, were included and followed with an average of 44 months (range 41-52 months). Both Schatzker and Müller classifications were used and was type II or 41-B3 in 7 patients, type III or 41-B2 in 12 patients, type IV or 41-C1 in 2 patients and type VI or 41-C3 in 3 patients, respectively. The joint alignement was satisfactory and manteined within a range of 2 mm, with an average of 1.18 mm. The mean Rasmussen knee function score was 26.5, with 14 patients having an excellent result and the remaining 10 with a good result. It can be concluded that radiological and clinical outcome was satisfactory and obtained in all cases without complications. This injectable novel biphasic hydroxyapatite and calcium sulfate ceramic material is a valuable armamentarium in the treatment of trauma where bone graft is required.

Site-specific adaptive remodeling of Greyhound metacarpal cortical bone subjected to asymmetrical cyclic loading.

PubMed

Johnson, K A; Skinner, G A; Muir, P

2001-05-01

To quantify geometric, inertial, and histomorphometric properties at the mid-diaphyseal level of left and right metacarpal bones (MCB) of racing Greyhounds. MCB from 7 racing Greyhounds euthanatized for reasons unrelated to MCB abnormalities. Mid-diaphyseal transverse sections of left and right MCB were stained with H&E or microradiographed. Images of stained sections were digitized, and cross-sectional area, cortical area, and maximum and minimum area moments of inertia of each bone were determined. Histomorphometric data (osteonal density, osteonal birefringence, and endosteal new lamellar bone thickness) were collected in 4 quadrants (dorsal, palmar, lateral, medial). Values were compared between limbs and among bones and quadrants. Cross-sectional area, cortical area, and maximum and minimum moments of inertia of left MCB-IV and -V were significantly greater, compared with contralateral bones. Overall osteonal densities in the dorsal quadrants of left MCB were greater, compared with lateral and medial quadrants. Also, percentage of birefringent osteons was significantly greater in the dorsal quadrant of left MCB-III, -IV, and -V, compared with the palmar quadrant. Thickness of new endosteal lamellar bone was not significantly influenced by limb, bone, or quadrant. Increased cortical thickness and geometric properties of left MCB-IV and -V of Greyhounds, together with altered turnover and orientation of osteons in the dorsal quadrants of left MCB, are site-specific adaptive responses associated with asymmetric cyclic loading as a result of racing on circular tracks. Site-specific adaptive remodeling may be important in the etiopathogenesis of fatigue fractures in racing Greyhounds.

Comparative ex vivo evaluation of two electronic percussive testing devices measuring the stability of dental implants.

PubMed

Geckili, Onur; Bilhan, Hakan; Cilingir, Altug; Bilmenoglu, Caglar; Ates, Gokcen; Urgun, Aliye Ceren; Bural, Canan

2014-12-01

A comparative ex vivo study was performed to determine electronic percussive test values (PTVs) measured by cabled and wireless electronic percussive testing (EPT) devices and to evaluate the intra- and interobserver reliability of the wireless EPT device. Forty implants were inserted into the vertebrae and forty into the pelvis of a steer, a safe distance apart. The implants were all 4.3 mm wide and 13 mm long, from the same manufacturer. PTV of each implant was measured by four different examiners, using both EPT devices, and compared. Additionally, the intra- and interobserver reliability of the wireless EPT device was evaluated. Statistically significant differences (P <0.05) were observed between PTVs made by the two EPT devices. PTVs measured by the wireless EPT device were significantly higher than the cabled EPT device (P <0.05), indicating lower implant stability. The intraobserver reliability of the wireless EPT device was evaluated as excellent for the measurements in type II bone and good-to-excellent in type IV bone; interobserver reliability was evaluated as fair-to-good in both bone types. The wireless EPT device gives PTVs higher than the cabled EPT device, indicating lower implant stability, and its inter- and intraobserver reliability is good and acceptable.

Rib Cage Deformities Alter Respiratory Muscle Action and Chest Wall Function in Patients with Severe Osteogenesis Imperfecta

PubMed Central

LoMauro, Antonella; Pochintesta, Simona; Romei, Marianna; D'Angelo, Maria Grazia; Pedotti, Antonio; Turconi, Anna Carla; Aliverti, Andrea

2012-01-01

Background Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. Methods Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. Results Both OI type III and IV patients showed reduced FVC and FEV1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01). In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01) angle at the sternum (pectus carinatum), paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001). Conclusions In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease. PMID:22558284

MANAGEMENT OF BILATERAL FEMORAL NECK FRACTURE IN A NONAGENARIAN PATIENT--CASE REPORT.

PubMed

Popescu, D; Trandabaţ, C; Puha, B; Veliceasa, B; Alexa, O

2016-01-01

Simultaneous bilateral femoral neck fracture is rare injury. Cases with this type of fracture have been reported in the literature since the 1950s, following the introduction of electroconvulsive therapy which generates violent hip muscle contractions. In young patients' simultaneous bilateral femoral neck fracture results from high energy trauma (car accident or fall from height) in a normal bone. Pathological changes in bone structure occurring in chronic kidney disease, vitamin D deficiency, osteomalacia, osteoporosis, metabolic imbalances and administration of corticosteroids explain the occurrence of this particular type of fracture following low-energy trauma. We present the case of a 90-year-old female patient who suffered a simple fall from her own height resulting in a Garden IV bilateral femoral neck fracture. Our therapeutic option in this patient was bilateral uncemented bipolar hemiarthroplasty in a single session using a single tray of sterile surgical instruments and two sterile drapes. Postoperative outcome was very good, allowing the initiation of functional recovery on the first postoperative day. Uncemented hemiarthroplasty proved to be a good choice in such a patient in the associated diseases may trigger the risk of cardiovascular disturbances specific to bone cement implantation syndrome.

Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

PubMed

Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

2017-02-01

An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs

PubMed Central

Klar, Roland M; Duarte, Raquel; Dix-Peek, Therese; Dickens, Caroline; Ferretti, Carlo; Ripamonti, Ugo

2013-01-01

Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca++ channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca++ activating stem cell differentiation and the induction of bone formation. PMID:24106923

Assessment of the correlation between insertion torque and resonance frequency analysis of implants placed in bone tissue of different densities.

PubMed

Filho, Luiz Carlos Magno; Cirano, Fabiano Ribeiro; Hayashi, Fernando; Feng, Hsu Shao; Conte, Alexandre; Dib, Luciano Lauria; Casati, Marcio Zaffalon

2014-06-01

The primary stability of dental implants is fundamental for osseointegration. Therefore, this study aimed to assess the correlation between insertion torque (IT) and resonance frequency analysis (RFA) of implants placed in mandibles and maxillas of different bone densities. Eighty dental implants were placed in maxillas and mandibles, and IT and the implant stability quotient (ISQ) were measured at the time of implant insertion. Bone density was assessed subjectively by the Lekholm and Zarb index. The type I and II densities were grouped together (group A)as were the type III and IV densities (group B). The IT in group A was higher (Student t test, P = .0013) than in group B (46.27 ± 18.51 Ncm, 33.62 ± 14.74 Ncm, respectively). The implants placed in group A showed higher ISQ (Student t test, P = .0004) than those placed in group B (70.09 ± 7.50, 63.66 ± 8.00, respectively). A significant correlation between IT and the ISQ value was observed for group A (Pearson correlation test; r = 0.35; P = .0213) and for group B (r = 0.37; P = .0224). Within the limitations of this study, it was possible to conclude that there is a correlation between IT and RFA of implants placed in mandibles and maxillas of different bone densities.

The role of single immediate loading implant in long Class IV Kennedy mandibular partial denture.

PubMed

Mohamed, Gehan F; El Sawy, Amal A

2012-10-01

The treatment of long-span Kennedy class IV considers a prosthodontic challenge. This study evaluated the integrity of principle abutments in long Kennedy class IV clinically and radiographically, when rehabilitated with conventional metallic partial denture as a control group and mandibular partial overdentures supported with single immediately loaded implant in symphyseal as a study group. Twelve male patients were divided randomly allotted into two equal groups. First group patients received removable metallic partial denture, whereas in the second group, patients received partial overdentures supported with single immediately loaded implant in symphyseal region. The partial dentures design in both groups was the same. Long-cone paralleling technique and transmission densitometer were used at the time of denture insertion, 3, 6, and 12 months. Gingival index, bone loss, and optical density were measured for principle abutments during the follow-up. A significant reduction in bone loss and density were detected in group II comparing with group I. Gingival index had no significant change (p-value < 0.05). A single symphyseal implant in long span class IV Kennedy can play a pivotal role to improve the integrity of the principle abutments and alveolar bone support. © 2010 Wiley Periodicals, Inc.

Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

ClinicalTrials.gov

2018-03-05

Breast Carcinoma Metastatic in the Bone; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

A High Serum Iron Level Causes Mouse Retinal Iron Accumulation Despite an Intact Blood-Retinal Barrier

PubMed Central

Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L.

2015-01-01

The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms. PMID:25174877

Identification of proteinaceous material in the bone of the dinosaur Iguanodon.

PubMed

Embery, Graham; Milner, Angela C; Waddington, Rachel J; Hall, Rachel C; Langley, Martin S; Milan, Anna M

2003-01-01

This study has directed attention at the search for bone-related proteins in an extract of demineralized rib bone of the 120 mya Iguanodon. The inner compact bone was demineralized and the GuCl extract resolved into 11 fractions using anion exchange chromatography, which all contained silver-reactive proteins with various amino acid profiles. Two specific fractions, iv and xi, revealed characteristics typical of contemporary phosphoproteins and proteoglycans, respectively. Fraction iv, 43-57 kDa, contained a high ratio of aspartate and serine, although no phosphate was discernable. Fraction xi contained a band of 41-47 kDa and was rich in chondroitin sulphate and hyaluronan. In addition an early eluting fraction was immunoreactive with an antibody against osteocalcin. A cancellous bone fraction from the same bone sample was also analyzed using N-terminal sequencing and revealed potential similarities with cystatin. While we do not claim to have identified the presence of intact proteins, this study has value in demonstrating that extruded extracellular matrix is protected by its capacity to induce mineralization, which subsequently is important in conserving detectable protein products in ancient skeletal tissues.

EFFECTS OF CHEMICAL PROCESSING AND OXIDE ETHYLENE STERILIZATION ON CORTICAL AND CANCELLOUS RAT BONE: A LIGHT AND ELECTRON SCANNING MICROSCOPY STUDY

PubMed Central

Castiglia, Marcello Teixeira; da Silva, Juliano Voltarelli F.; Frezarim Thomazini, José Armendir; Volpon, José Batista

2015-01-01

To evaluate, under microscopic examination, the structural changes displayed by the trabecular and cortical bones after being processed chemically and sterilized by ethylene oxide. Methods: Samples of cancellous and cortical bones obtained from young female albinus rats (Wistar) were assigned to four groups according to the type of treatment: Group I- drying; Group II- drying and ethylene oxide sterilization; III- chemical treatment; IV- chemical treatment and ethylene oxide sterilization. Half of this material was analyzed under ordinary light microscope and the other half using scanning electron microscopy. Results: In all the samples, regardless the group, there was good preservation of the general morphology. For samples submitted to the chemical processing there was better preservation of the cellular content, whereas there was amalgamation of the fibres when ethylene oxide was used. Conclusion: Treatment with ethylene oxide caused amalgamation of the fibers, possibly because of heating and the chemical treatment contributed to a better cellular preservation of the osseous structure. PMID:26998450

Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5

PubMed Central

Schorr, Melanie; Thomas, Jennifer J.; Eddy, Kamryn T.; Dichtel, Laura E.; Lawson, Elizabeth A.; Meenaghan, Erinne; Paskal, Margaret Lederfine; Fazeli, Pouneh K.; Faje, Alexander T.; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K.

2016-01-01

Objective DSM-5 revised diagnostic criteria for anorexia nervosa (AN) by eliminating the amenorrhea requirement, liberalizing weight and psychological criteria, and adding the formal diagnosis of “atypical AN” for individuals with AN psychological symptoms without low weight. We sought to determine whether bone density (BMD) is impaired in women diagnosed with AN using the new, more liberal DSM-5 criteria. Method Cross-sectional study of 168 women, 18–45y: 1) AN by DSM-IV (DSM-IV)(n=37), 2) AN by DSM-5 but not DSM-IV criteria (DSM-5)(n=33), 3) atypical AN (ATYPICAL)(n=77), 4) healthy comparison group (HC)(n=21). Measurements included dual energy x-ray absorptiometry, Eating Disorder Examination-Questionnaire, Eating Disorder Inventory-2, Hamilton Depression and Anxiety Rating Scales. Results BMD Z-score <−1.0 was present in 78% of DSM-IV, 82% of DSM-5, and 69% of ATYPICAL. Mean Z-scores were comparably low in DSM-IV and DSM-5, intermediate in ATYPICAL, and highest in HC. Lack of prior low weight or amenorrhea was, but history of overweight/obesity was not, protective against bone loss. Mean lean mass and percent fat mass were significantly lower in all AN groups than HC. DSM-IV, DSM-5 and ATYPICAL had comparable psychopathology. Discussion Despite liberalizing diagnostic criteria, many women diagnosed with AN and atypical AN using DSM-5 criteria have low BMD. Presence or history of low weight and/or amenorrhea remain important indications for DXA. Loss of lean mass, in addition to fat mass, is present in all AN groups, and may contribute to low BMD. The deleterious effect of eating disorders on BMD extends beyond those with current low weight and amenorrhea. PMID:27527115

A simple technique to strengthen the initial and mid-term to long-term stability of the cup during total hip arthroplasty in developmental dysplasia of the hip.

PubMed

Guan, Mingqiang; Zhou, Guanming; Li, Xue

2018-04-01

To assess the effects of a technique of cup blocking screws combined with impaction bone grafting during total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH). From August 2011 to July 2015, 53 patients (59 hips) with DDH in our hospital were treated with THA using the technique of cup blocking screws combined with impaction particulate bone grafting. These patients were prospectively followed, and the clinical and imaging results were collected. Harris hip score (HHS) was raised from 41.24 before surgery to 91.49 at the latest follow-up (p less than 0.001). Length discrepancy (LLD) was reduced from 28.97 mm before surgery to 6.08 mm after surgery (p less than 0.001). No loosening of the cup was detected at the last follow-up. The differences were insignificant in cup inclination and rate of cup coverage among the 3 groups of Crowe type II, type III, and type IV DDH (p greater than 0.05). The technique of cup blocking screws combined with impaction particulate bone grafting is simple and reliable, and it not only simplifies the attainment of initial stability, but also strengthens the mid-term to long-term stability during THA in DDH.

Guided tissue regeneration with heterologous materials in primary subtalar arthrodesis: a case report.

PubMed

Frangez, Igor; Kasnik, Tea; Cimerman, Matej; Smrke, Dragica Maja

2016-05-03

Calcaneal fractures are relatively rare and difficult to treat. Treatment options vary based on the type of fracture and the surgeon's experiences. In recent years, surgical procedures have increasingly been used due to the better long-term results. We present a case where guided tissue regeneration was performed in a calcaneal fracture that needed primary subtalar arthrodesis. We used the principles of guided tissue regeneration from oral surgery to perform primary subtalar arthrodesis and minimize the risk of non-union. We used a heterologous collagen membrane, which acts as a mechanical barrier and protects the bone graft from the invasion of unwanted cells that could lead to non-union. The collagenous membrane also has osteoconductive properties and is therefore able to increase the osteoblast proliferation rate. A 62-year-old Caucasian woman sustained multiple fractures of her lower limbs and spine after a fall from a ladder. Her left calcaneus had a comminuted multifragmental fracture (Sanders type IV) with severe destruction of the cartilage of her subtalar joint and depression of the Böhler's angle. Therefore, we performed primary arthrodesis of her subtalar joint with elevation of the Böhler's angle using a 7.3 mm titanium screw, a heterologous cortico-cancellous collagenated pre-hydrated bone mix, a heterologous cancellous collagenated bone wedge, and a heterologous collagen membrane (Tecnoss®, Italy). The graft was fully incorporated 12 weeks after the procedure and a year and a half later our patient walks without limping. We present a new use of guided tissue regeneration with heterologous materials that can be used to treat extensive bone defects after bone injuries. We believe that guided tissue regeneration using heterologous materials, including a heterologous collagen membrane that presents a mechanical barrier between soft tissues and bone as well as a stimulative component that enhances bone formation, could be more often used in bone surgery.

[Symbrachydactyly].

PubMed

Samson, P; Mevio, G

2008-12-01

Symbrachydactyly is literally defined as a combination of short fingers with syndactyly. Blauth and Gekeler described four types of symbrachydactyly, ranging from simple shortness of middle phalanges to complete absence of digital rays. In type I (short finger) function is quite normal and syndactyly release is usually the only procedure needed. In type II (cleft hand), presence of a thumb and at least one ulnar finger allows pinch function. Surgical treatment, when needed, consists in separation of webbed fingers, resection of nonfunctional digital stumps, or finger translocation. In type III (monodactyly) all long fingers are absent. Pinch function can be created between the thumb and a toe transfer in ulnar location. Bone lengthening is an alternative procedure to create a pincer. Surgery is not always indicated in type IV (peromely) as function can only be restored if active motion is already present at wrist or carpometacarpal levels.

Screw fixation versus arthroplasty versus plate fixation for 3-part radial head fractures.

PubMed

Wu, P H; Shen, L; Chee, Y H

2016-04-01

To compare the outcome following headless compression screw fixation versus radial head arthroplasty versus plate fixation for 3-part Mason types III or IV radial head fracture. Records of 25 men and 16 women aged 21 to 80 (mean, 43.3) years who underwent fixation using 2 to 3 2-mm cannulated headless compression screws (n=16), radial head arthroplasty (n=13), or fixation with a 2-mm Synthes plate (n=12) for 3-part Mason types III or IV radial head and neck fracture were reviewed. Treatment option was decided by the surgeon based on the presence of associated injury, neurovascular deficit, and the Mason classification. Bone union, callus formation, and complications (such as heterotopic ossification, malunion, and nonunion) were assessed by an independent registrar or consultant using radiographs. The Mayo Elbow Performance Score and range of motion were assessed by an independent physiotherapist. The median age of the 3 groups were comparable. Associated injuries were most common in patients with arthroplasty, followed by screw fixation and plate fixation (61.5% vs. 50% vs. 33%, p=0.54). The median time to bone union was shorter after screw fixation than plate fixation (55 vs. 86 days, p=0.05). No patient with screw fixation had nonunion, but 4 patients with plate fixation had nonunion. The 3 groups were comparable in terms of the mean Mayo Elbow Performance Score (p=0.56) and the mean range of motion (p=0.45). The complication rate was highest after plate fixation, followed by screw fixation and arthroplasty (50% vs. 18.8% vs. 15.4%, p=0.048). Excluding 20 patients with associated injuries (8 in screw fixation, 8 in arthroplasty, and 4 in plate fixation), the 3 groups were comparable in terms of the median time to bone union (p=0.109), mean Mayo Elbow Performance Score (p=0.260), mean range of motion (p=0.162), and complication rate (p=0.096). Headless compression screw fixation is a viable option for 3-part radial head fracture. It achieves earlier bone union with fewer complications.

Biomechanical study of pelvic discontinuity in failed total hip arthroplasty. Lessons learnt from the treatment of pelvic fractures.

PubMed

Ribes-Iborra, Julio; Atienza, Carlos; Sevil-De la Torre, Jorge; Gómez Pérez, Amelia

2017-11-01

Pelvic discontinuity is a rare but serious problem in orthopedic surgery. Acetabular reconstruction in case of severe bone loss after failed total hip arthroplasty is technically difficult, especially in segmental loss type III (anterior or posterior) or pelvic discontinuity (type IV). Acetabular reinforcement devices are frequently used as load-sharing devices to allow allograft incorporation and in order to serve as support of acetabular implants. This study tries to show, by means of biomechanic work, the efficiency of reinforced plate in anterior column in a segmental pelvic loss, illustrated with a clinical case, which shows the socket stability of hip prosthesis. © 2017 Elsevier Ltd. All rights reserved.

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation.

PubMed

Mustansar, Zartasha; McDonald, Samuel A; Sellers, William Irvin; Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J; Margetts, Lee

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone's internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms.

[Histopathological diagnostic work-up of joint endoprosthesis-associated pathologies].

PubMed

Krenn, V; Perino, G; Krenn, V T; Wienert, S; Saberi, D; Hügle, T; Hopf, F; Huber, M

2016-05-01

Increasing classes of joint implants and the combination of materials results in increased and wear-associated pathologies. According to the revised consensus classification, the following types can be recognized at conventional histological examination: Type I, particle-induced type; Type II, infection type; Type III, combination type; Type IV, indifferent type; Type V arthrofibrotic type; Type VI, allergic/immunological/toxic adverse reactions and Type VII, bone pathologies. Wear particles are histopathologically characterized according to the Krenn particle algorithm which focuses on a descriptive identification of wear particles and the differentiation of other nonwear-related particles. Type VII is considered histologically when there is evidence of a perivascular/interstitial lymphocytic CD20- and CD3-positive infiltrate, presence of mast cells and eosinophils, and tissue necrosis/infarction associated with implant wear material. Since wear particle-induced toxicity cannot be differentiated with certainty from hypersensitivity/allergic reaction on histological examination, immunological-allergological and clinical data should be used as supplementary criteria for the differential diagnosis. Tissue sampling should be performed from periprosthetic soft tissue with location mapping and when feasible also from bone tissue. Additional information regarding the type of implant and clinical, radiological, immunological, and microbiology data should be available to the pathologist. Further immunohistochemical studies are recommended in the following settings: infection (CD15, CD20, CD68); prosthesis-associated arthrofibrosis (β‑catenin); allergic/immunologic/toxic adverse reactions (CD20, CD3, CD4, CD8, CD117 and for T‑cell characterization T‑bet, GATA-3, and FOXP3).

Long-Term Survival of Dental Implants with Different Prosthetic Loading Times in Healthy Patients: A 5-Year Retrospective Clinical Study.

PubMed

Muelas-Jiménez, M Isabel; Olmedo-Gaya, Maria Victoria; Manzano-Moreno, Francisco J; Reyes-Botella, Candela; Vallecillo-Capilla, Manuel

2017-02-01

To compare survival rates among dental implants restored with immediate, early, and conventional loading protocols, also comparing between maxillary and mandibular implants, and to evaluate the influence of implant length and diameter and the type of prosthesis on treatment outcomes. This retrospective cohort study initially included all 52 patients receiving dental implants between July 2006 and February 2008 at a private oral surgery clinic in Granada (Southern Spain). Clinical and radiographic examinations were performed, including periapical or panoramic radiographs, and incidences during completion of the restoration were recorded at 1 week, 3 months, 6 months, and at 1, 2, 3, 4, and 5 years. After a 5-year follow-up, 1 patient had died, 3 were lost to follow-up, and 6 required grafting before implant placement; therefore, the final study sample comprised 42 patients with 164 implants. Variables associated with the survival/failure of the restoration were: number of implants (higher failure rate with fewer implants), bone type (higher failure rate in type III or IV bone), and type of prosthesis (higher failure rate with single crowns). No significant association was found in univariate or multivariate analyses between survival rate and the loading protocol, implant length or diameter, or maxillary/mandibular location. Immediate occlusal loading, immediate provisionalization without occlusal loading, and early loading are viable treatment options with similar survival rates to those obtained with conventional loading. Bone quality and number of implants per patient were the most influential factors. © 2015 by the American College of Prosthodontists.

Endoglin (CD105) expression differentiates between aseptic loosening and periprosthetic joint infection after total joint arthroplasty.

PubMed

Jansen, Philipp; Mumme, Torsten; Randau, Thomas; Gravius, Sascha; Hermanns-Sachweh, Benita

2014-01-01

The differentiation between aseptic loosening and periprosthetic joint infection (PJI) after total joint arthroplasty is essential for successful therapy. A better understanding of pathogenesis of aseptic loosening and PJI may help to prevent or treat these complications. Previous investigations revealed an increased vascularization in the periprosthetic membrane in cases of PJI via PET signals. Based on these findings our hypothesis was that PJI is associated with an increased neovascularization in the periprosthetic membrane. Tissue samples from periprosthetic membranes of the bone-implant interface were investigated histologically for inflammation, wear particles, vascularization and fibrosis. To identify vascular structures antibodies against CD 31, CD 34, factor VIII and CD 105 (endoglin) were applied for immunohistochemical investigations. According to a consensus classification of Morawietz the tissue samples were divided into four types: type I (wear particle induced type, n = 11), type II (infectious type, n = 7), type III (combined type, n = 7) and type IV (indeterminate type, n = 7). Patients with PJI (type II) showed a pronounced infiltration of neutrophil granulocytes in the periprosthetic membrane and an enhanced neovascularization indicated by positive immunoreaction with antibodies against CD 105 (endoglin). Tissue samples classified as type I, type III and type IV showed significantly less immune reaction for CD 105. In cases of aseptic loosening and PJI vascularization is found in different expression in periprosthetic membranes. However, in aseptic loosening, there is nearly no neovascularization with CD 105-positive immune reaction. Therefore, endoglin (CD 105) expression allows for differentiation between aseptic loosening and PJI.

[The spectrum of histomorphological findings related to joint endoprosthetics].

PubMed

Morawietz, L; Krenn, V

2014-11-01

Approximately 230,000 total hip and 170,000 knee joint endoprostheses are implanted in Germany annually of which approximately 10% (i.e. 40,000 interventions per year) are cases of revision surgery. These interventions involve removal of a previously implanted prosthesis which has resulted in complaints and replacement with a new prosthesis. There are manifold reasons for revision surgery, the most common indication being so-called endoprosthesis loosening, which is subdivided into septic and aseptic loosening. Histomorphological studies revealed that periprosthetic tissue from endoprosthesis loosening can be classified into four types (I) wear-particle induced type, (II) infectious type, (III) combined type and (IV) fibrous type. Types I and IV represent aseptic loosening and types II and III septic loosening. Recently, the topic of implant allergy has emerged. The detection of cellular, mostly perivascular lymphocytic infiltrates is discussed as being a sign of an allergic tissue reaction. It has most frequently been observed in type I periprosthetic membranes with a dense load of metal wear, which occurs with metal-on-metal bearings. Apart from endoprosthesis loosening, arthrofibrosis is another complication of joint endoprosthetics and can cause pain and impaired function. Histopathologically, arthrofibrosis can be evaluated by a three-tiered grading system. Furthermore, bone pathologies, such as ossification, osteopenia or osteomyelitis can occur as complications of joint endoprosthetics. This review gives an overview of the whole spectrum of pathological findings in joint endoprosthetics and offers a comprehensive and standardized classification system for routine histopathological diagnostics.

Surgery versus surgery plus pamidronate in the management of osteogenesis imperfecta patients: a comparative study.

PubMed

el-Sobky, Mohammed A; Hanna, Atef A Zaky; Basha, Naguib E; Tarraf, Yehia N; Said, May H

2006-05-01

The aim of this study was to evaluate the efficacy of pamidronate in the management of osteogenesis imperfecta patients. This study was carried out in two groups. The first was treated only surgically whereas the second was treated by a combined approach, medical and surgical. Forty patients, divided into two groups, were surgically treated in order to correct bony deformities secondary to osteogenesis imperfecta. Group 1: twenty patients were operated at an average age of 6.5 years. Nine were type I, five type III and six type IV. Group 2: this group consisted of 20 patients to whom intermittent intravenous pamidronate were given at regular intervals for an average of 2 years postoperatively. The average age at surgery was 8.5 years. Four patients were type I, six type III, eight type IV, one type V and the remaining one type VII. The results were assessed according to a scoring system suggested and used by the authors since 1999. Group 1: we had three good, nine fair and eight poor results. Group 2: we had 11 excellent, four good and five fair results. The Bone mineral dens (BMD) increased by an average of 35.2% (22.7-112%), and the rate of refracture decreased. Best results in the management of patients can be obtained through the combined approach (surgical and medical treatment). We now advise preoperative and postoperative pamidronate for these patients.

Management of Nonunited Talar Fractures With Avascular Necrosis by Resection of Necrotic Bone, Bone Grafting, and Fusion With an Intramedullary Nail.

PubMed

Abd-Ella, Mohamed Mokhtar; Galhoum, Ahmed; Abdelrahman, Amr Farouk; Walther, Markus

2017-08-01

The presence of nonunion of a talar fracture with displacement, together with complete avascular necrosis, is a challenging entity to treat. Twelve patients, 8 men (66.7%) and 4 women (33.3%), with nonunited talar fractures and extensive avascular necrosis of the talus were included. The average age was 27.7 years (range, 19-38 years). After exclusion of infection, the patients underwent resection of necrotic bone, bulk autograft, and fusion using an intramedullary nail. The posterior approach was used in 11 patients and the anterior approach in 1 patient. The primary outcome was solid osseous union at the ankle and subtalar level and between the talar head anteriorly and the posterior construct, as evidenced by computed tomographic examination. Functional assessment was performed with the American Orthopaedic Foot & Ankle Society score and subjective patient satisfaction Results: After a mean follow-up duration of 23 months (range, 12-60 months), solid osseous union was achieved in 8 patients (66.7%). Stable fibrous union was seen in 1 patient (8.3%). Three patients (25%) required reoperation, and osseous fusion was finally achieved. American Orthopaedic Foot & Ankle Society score improved from a mean of 39.3 (range, 12-56) preoperatively to 76.6 (range, 62-86) at last follow-up. Subjective patient satisfaction was graded good or excellent in all cases. Resection of necrotic talar body and bulk autograft with tibiotalocalcaneal fusion by an intramedullary nail through a posterior approach was a reasonable option for the management of type IV posttraumatic talar deformity. Level IV, case series.

Cell metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

NASA Astrophysics Data System (ADS)

Milgram, S.; Carrière, M.; Thiebault, C.; Berger, P.; Khodja, H.; Gouget, B.

2007-07-01

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se IV and Cu as the most toxic and Ni, Se VI, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

Beneficial effects of intravenous pamidronate treatment in children with osteogenesis imperfecta under 24 months of age.

PubMed

Kusumi, Kirsten; Ayoob, Rose; Bowden, Sasigarn A; Ingraham, Susan; Mahan, John D

2015-09-01

Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility and low bone mass. Low bone density and fracture is a cause of morbidity. Limited data exists on bisphosphonate treatment in patients under 24 months of age. The objective of the study was to examine the safety and efficacy of pamidronate in children under 24 months with OI. To do so, we carried out a retrospective chart review and analysis of OI patients started on intravenous pamidronate under 24 months of age. Pamidronate was administered in three-day cycles. Growth, the number of fractures, and lumbar bone mineral densities were recorded both prior to and after treatment initiation. A total of 18 patients were reviewed. Five were classified as OI type I, seven were type III, and six were type IV. The mean age at treatment initiation was 12 months (range 11 days to 23 months). The mean lumbar z score at baseline was -3.63, which improved to -1.53 at one year (P < 0.01) and 0.79 (P < 0.01) at the end of the study. The fracture rate improved from 68 fractures in 209 months (0.32 fractures/patient-month) before treatment to 41 fractures in 1,248 months (0.03 fractures/patient-month) post-treatment (P < 0.05). Height standard deviation score (SDS) was conserved from baseline to end of study (-2.12 ± 2.45 vs. -2.45 ± 2.73) (P = 0.05) with an average follow-up of 73 months. The only adverse effect recorded in six infants was fever during the initial pamidronate infusion. Treatment with intravenous pamidronate is safe, significantly improves lumbar bone mineral density (L-BMD), and reduces fracture rates in young infants with OI while preserving linear growth.

[Proposal for the classification of the periprosthetic membrane from loosened hip and knee endoprostheses].

PubMed

Morawietz, L; Gehrke, Th; Classen, R-A; Barden, B; Otto, M; Hansen, T; Aigner, Th; Stiehl, P; Neidel, J; Schröder, J H; Frommelt, L; Schubert, Th; Meyer-Scholten, C; König, A; Ströbel, Ph; Rader, Ch P; Kirschner, S; Lintner, F; Rüther, W; Skwara, A; Bos, I; Kriegsmann, J; Krenn, V

2004-09-01

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.

Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

PubMed

Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

2016-05-01

Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5.

PubMed

Schorr, Melanie; Thomas, Jennifer J; Eddy, Kamryn T; Dichtel, Laura E; Lawson, Elizabeth A; Meenaghan, Erinne; Lederfine Paskal, Margaret; Fazeli, Pouneh K; Faje, Alexander T; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K

2017-04-01

DSM-5 revised the diagnostic criteria for anorexia nervosa (AN) by eliminating the amenorrhea requirement, liberalizing weight and psychological criteria, and adding the formal diagnosis of "atypical AN" for individuals with AN psychological symptoms without low weight. We sought to determine whether bone density (BMD) is impaired in women diagnosed with AN using the new, more liberal, DSM-5 criteria. Cross-sectional study of 168 women, 18 - 45y: (1) AN by DSM-IV (DSM-IV AN) (n = 37), (2) AN by DSM-5 but not DSM-IV criteria (DSM-5 AN) (n = 33), (3) atypical AN (ATYPICAL AN) (n = 77), (4) healthy comparison group (HC) (n = 21). Measurements included dual energy X-ray absorptiometry, Eating Disorder Examination-Questionnaire, Eating Disorder Inventory-2, Hamilton Depression and Anxiety Rating Scales. BMD Z-score <-1.0 was present in 78% of DSM-IV, 82% of DSM-5, and 69% of ATYPICAL. Mean Z-scores were comparably low in DSM-IV and DSM-5, intermediate in ATYPICAL, and highest in HC. Lack of prior low weight or amenorrhea was, but history of overweight/obesity was not, protective against bone loss. Mean lean mass and percent fat mass were significantly lower in all AN groups than HC. DSM-IV, DSM-5, and ATYPICAL had comparable psychopathology. Despite liberalizing diagnostic criteria, many women diagnosed with AN and atypical AN using DSM-5 criteria have low BMD. Presence or history of low weight and/or amenorrhea remain important indications for DXA. Loss of lean mass, in addition to fat mass, is present in all AN groups, and may contribute to low BMD. The deleterious effect of eating disorders on BMD extends beyond those with current low weight and amenorrhea. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:343-351). © 2016 Wiley Periodicals, Inc.

Evaluating the Implementation Barriers of an Intranasal Fentanyl Pain Pathway for Pediatric Long-Bone Fractures.

PubMed

Arnautovic, Tamara; Sommese, Kathryn; Mullan, Paul C; Frazier, Steven Barron; Vazifedan, Turaj; Ramirez, Dana Erikson

2017-12-01

This study aimed to assess physician comfort, knowledge, and implementation barriers regarding the use of intranasal fentanyl (INF) for pain management in patients with long-bone fractures in a pediatric emergency department (ED) with an INF pain pathway. A retrospective chart review was conducted of patients, 3 to 21 years old, in our ED with an International Classification of Diseases-9th Revision code for a long-bone fracture from September 1, 2013, to August 31, 2015. Patients were divided into 4 groups: (1) received INF on the pathway appropriately; (2) "missed opportunities" to receive INF, defined as either INF was ordered and then subsequently canceled (for pain ratings, ≥6/10), or INF was ordered, cancelled, and intravenous (IV) morphine given, or INF was not ordered and a peripheral IV line was placed to give IV morphine as first-line medication; (3) peripheral IV established upon ED arrival; (4) no pain medication required. Additionally, a survey regarding practice habits for pain management was completed to evaluate physician barriers to utilization of the pathway. A total of 1374 patients met the inclusion criteria. Missed opportunities were identified 41% of the time. Neither younger patient age nor more years of physician experience in the ED were associated with increased rates of missed opportunities. The survey (95% response rate) revealed greater comfort with and preference for IV morphine over INF. The high rate of missed opportunities, despite the implementation of an INF pain pathway, indicates the need for further exploration of the barriers to utilization of the INF pain pathway.

Is there a simple, definitive, and cost-effective way to diagnose osteomyelitis in the pressure ulcer patient?

PubMed

Larson, David L; Gilstrap, Jarom; Simonelic, Kevin; Carrera, Guillermo F

2011-02-01

Despite advances in managing pressure ulcers, there is still no definitive way to diagnose bone infection (osteomyelitis) short of open biopsy. An effective, less invasive diagnostic method might result in cost savings and improved care; however, needle aspiration, computed tomography scan, magnetic resonance imaging, ultrasound, and bone scans have proven unsatisfactory in predicting osteomyelitis. The authors reviewed preoperative radiologic studies of stage IV pressure ulcer patients and their bone biopsy results to determine which radiologic studies are most diagnostic for osteomyelitis. Patients (n = 44) having surgical débridement of stage IV ulcers with open bone biopsy after prior radiographic imaging (plain films, ultrasound, computed tomography, magnetic resonance imaging, and/or nuclear bone scans) were included. Studies were interpreted by a single musculoskeletal radiologist blinded to information from the medical record and following standard radiologic criteria for the diagnosis of osteomyelitis. The percentage of patients with biopsy-proven osteomyelitis identified with imaging was 50 percent using a computed tomography scan and 88 percent using a plain film of the bony area of involvement. The overall sensitivity of either radiologic study was 61 percent. The percentage of patients without osteomyelitis identified as not having the condition by imaging was 85 percent for the computed tomography scan and 32 percent for the plain film. Overall specificity of both studies was 69 percent. Preoperative radiologic studies for osteomyelitis in a pressure ulcer are far from definitive; however, if a radiologic study is used to make that diagnosis in a stage IV pressure ulcer, it would appear that a plain film would suffice.

Reconstruction of maxillectomy and midfacial defects with free tissue transfer.

PubMed

Santamaria, Eric; Cordeiro, Peter G

2006-11-01

The maxillary bones are part of the midfacial skeleton and are closely related to the eyeglobe, nasal airway, and oral cavity. Together with the overlying soft tissues, the two maxillae are responsible to a large extent for facial contour. Maxillectomy defects become more complex when critical structures such as the orbit, globe, and cranial base are resected, and reconstruction with distant tissues become essential. In this article, we describe a classification system and algorithm for reconstruction of these complex defects using various pedicled and free flaps. Most defects that involve resection of the maxilla and adjacent soft tissues may be classified into one of the following four types: Type I defects, Limited maxillectomy; Type II defects, Subtotal maxillectomy; Type III defects, Total maxillectomy; and Type IV defects, Orbitomaxillectomy. Using this classification, reconstruction of maxillectomy and midfacial defects may be approached considering the relationship between volume and surface area requirements, that is, addressing the bony defect first, followed by assessment of the associated soft tissue, skin, palate, and cheek-lining deficits. In our experience, most complex maxillectomy defects are best reconstructed using free tissue transfer. The rectus abdominis and radial forearm free flap in combination with immediate bone grafting or as an osteocutaneous flap reliably provide the best aesthetic and functional results. A temporalis muscle pedicled flap is used for reconstruction of maxillectomy defects only in those patients who are not candidates for a microsurgical procedure.

Functionalization of deproteinized bovine bone with a coating-incorporated depot of BMP-2 renders the material efficiently osteoinductive and suppresses foreign-body reactivity.

PubMed

Wu, Gang; Hunziker, Ernst B; Zheng, Yuanna; Wismeijer, Daniel; Liu, Yuelian

2011-12-01

The repair of critical-sized bony defects remains a challenge in the fields of implantology, maxillofacial surgery and orthopaedics. As an alternative bone-defect filler to autologous bone grafts, deproteinized bovine bone (DBB) is highly osteoconductive and clinically now widely used. However, this product suffers from the disadvantage of not being intrinsically osteoinductive. In the present study, this property was conferred by coating DBB with a layer of calcium phosphate into which bone morphogenetic protein 2 (BMP-2) was incorporated. Granules of DBB bearing a coating-incorporated depot of BMP-2--together with the appropriate controls (DBB bearing a coating but no BMP-2; uncoated DBB bearing adsorbed BMP-2; uncoated DBB bearing no BMP-2)--were implanted subcutaneously in rats. Five weeks later, the implants were withdrawn for a histomorphometric analysis of the volume densities of (i) bone, (ii) bone marrow, (iii) foreign-body giant cells and (iv) fibrous capsular tissue. Parameters (i) and (ii) were highest, whilst parameters (iii) and (iv) were lowest in association with DBB bearing a coating-incorporated depot of BMP-2. Hence, this mode of functionalization not only confers DBB with the property of osteoinductivity but also improves its biocompatibility--thus dually enhancing its clinical potential in the repair of bony defects. Copyright © 2011 Elsevier Inc. All rights reserved.

Displacement of dental implants in trabecular bone under a static lateral load in fresh bovine bone.

PubMed

Engelke, Wilfried; Müller, Alois; Decco, Oscar A; Rau, María J; Cura, Andrea C; Ruscio, Mara L; Knösel, Michael

2013-04-01

The study aims to provide objective data for the displacement of titanium screw implants in trabecular bone specimens. One hundred Semados implants (Bego, Bremen, Germany) were inserted in bovine type IV bone specimens. All implants had a diameter of 3.75 mm; 50 implants had a length of 8.5 mm and 50 implants had a length of 15 mm. Insertion torque was determined at intervals of 10, 20, and 30 Ncm. Implants were loaded horizontally with 10, 20, and 30 N for 2 seconds. An indicator strip was attached to the implant abutment to allow direct observation of implant movement relative to the bone surface. Horizontal displacement was assessed with an accuracy of measurement of 10 µm. Seven implants got lost by visible loosening. Degree of displacement was subject to evaluation with all others. Those implants showed a mean displacement of 59 µm for 10 N (n = 100), 173 µm for 20 N (n = 99), and 211 µm for 30 N (n = 93). The mean displacement of 15-mm implants (16, 37, 51 µm) was significantly lower compared with 8.5-mm implants (103, 311, 396 µm) corresponding to 10, 20, and 30 N as lateral loads. Displacement of screw implants in trabecular bone can be detected and visualized using commercially available endoscopes with a high magnification. A lateral load of 20 N indicates a mean displacement of over 100 µm and therefore results in a critical displacement. © 2011 Wiley Periodicals, Inc.

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation

PubMed Central

Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J.

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone’s internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms. PMID:28652932

Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

ClinicalTrials.gov

2018-02-27

Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis.

PubMed

Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

2014-09-18

Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group). Histologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group. Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more advantageous approach than systemic administration. Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA.

Fabrication of Metallic Biomedical Scaffolds with the Space Holder Method: A Review

PubMed Central

Arifvianto, Budi; Zhou, Jie

2014-01-01

Bone tissue engineering has been increasingly studied as an alternative approach to bone defect reconstruction. In this approach, new bone cells are stimulated to grow and heal the defect with the aid of a scaffold that serves as a medium for bone cell formation and growth. Scaffolds made of metallic materials have preferably been chosen for bone tissue engineering applications where load-bearing capacities are required, considering the superior mechanical properties possessed by this type of materials to those of polymeric and ceramic materials. The space holder method has been recognized as one of the viable methods for the fabrication of metallic biomedical scaffolds. In this method, temporary powder particles, namely space holder, are devised as a pore former for scaffolds. In general, the whole scaffold fabrication process with the space holder method can be divided into four main steps: (i) mixing of metal matrix powder and space-holding particles; (ii) compaction of granular materials; (iii) removal of space-holding particles; (iv) sintering of porous scaffold preform. In this review, detailed procedures in each of these steps are presented. Technical challenges encountered during scaffold fabrication with this specific method are addressed. In conclusion, strategies are yet to be developed to address problematic issues raised, such as powder segregation, pore inhomogeneity, distortion of pore sizes and shape, uncontrolled shrinkage and contamination. PMID:28788638

[Phakomatosis pigmento-vascularis. Report of 2 cases associated with angiodysplasia].

PubMed

Peyron, N; Dereure, O; Bessis, D; Guilhou, J J; Guillot, B

1993-01-01

Phakomatosis pigmentovascularis is an uncommon disease, with a peculiar association of capillary hemangioma and pigmented lesions. Four entities have to date been described (I to IV), with localized (a) or systematical (b) involvement. In this latter subtype, the cutaneous lesions are associated with visceral (eye, central nervous system) and bony abnormalities. We describe two additional cases of phakomatosis pigmentovascularis type II (b) associated with a Klippel-Trenaunay syndrome. These reports emphasize the frequent occurrence of angiodysplasia of the Klippel-Trenaunay or Sturge-Weber-Krabbe type in the systemic subtype, especially II (b). Accordingly, complete investigations are warranted in all cases, with special attention for bones and some internal organs like eye and central nervous system. Pathophysiological hypothesis for phakomatosis pigmentovascularis are discussed.

Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

ClinicalTrials.gov

2017-12-04

Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

Clinical application of bone morphogenetic proteins for bone healing: a systematic review.

PubMed

Krishnakumar, Gopal Shankar; Roffi, Alice; Reale, Davide; Kon, Elizaveta; Filardo, Giuseppe

2017-06-01

This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

Non-vascularized iliac bone grafting for scaphoid nonunion with avascular necrosis.

PubMed

Kim, Jihyeung; Park, Jin Woo; Chung, Jeehyeok; Jeong Bae, Kee; Gong, Hyun Sik; Baek, Goo Hyun

2018-01-01

We present the surgical outcomes of non-vascularized bone grafting taken from the iliac crest in 24 patients with scaphoid nonunion and avascular necrosis. The Fisk-Fernandez technique was used in 11 patients, and cancellous bone grafting was used in 13 patients. Bony union was achieved in 22 of the 24 patients. Non-vascularized iliac bone grafting can be used for the surgical management of scaphoid nonunion with avascular necrosis. Although revascularization of the proximal fragment after surgery was not evaluated, bony union was confirmed in nearly all patients. IV.

Ultrastructure Organization of Human Trabeculae Assessed by 3D sSAXS and Relation to Bone Microarchitecture

PubMed Central

Guizar-Sicairos, Manuel; Gschwend, Oliver; Hangartner, Peter; Bunk, Oliver; Müller, Ralph; Schneider, Philipp

2016-01-01

Although the organization of bone ultrastructure, i.e. the orientation and arrangement of the mineralized collagen fibrils, has been in the focus of research for many years for cortical bone, and many models on the osteonal arrangement have been proposed, limited attention has been paid to trabecular bone ultrastructure. This is surprising because trabeculae play a crucial role for the mechanical strength of several bone sites, including the vertebrae and the femoral head. On this account, we first validated a recently developed method (3D sSAXS or 3D scanning small-angle X-ray scattering) for investigating bone ultrastructure in a quantitative and spatially resolved way, using conventional linearly polarized light microscopy as a gold standard. While both methods are used to analyze thin tissue sections, in contrast to polarized light microscopy, 3D sSAXS has the important advantage that it provides 3D information on the orientation and arrangement of bone ultrastructure. In this first study of its kind, we used 3D sSAXS to investigate the ultrastructural organization of 22 vertebral trabeculae of different alignment, types and sizes, obtained from 4 subjects of different ages. Maps of ultrastructure orientation and arrangement of the trabeculae were retrieved by stacking information from consecutive 20-μm-thick bone sections. The organization of the ultrastructure was analyzed in relation to trabecular microarchitecture obtained from computed tomography and to relevant parameters such as distance to trabecular surface, local curvature or local bone mineralization. We found that (i) ultrastructure organization is similar for all investigated trabeculae independent of their particular characteristics, (ii) bone ultrastructure exhibiting a high degree of orientation was arranged in domains, (iii) highly oriented ultrastructural areas were located closer to the bone surface, (iv) the ultrastructure of the human trabecular bone specimens followed the microarchitecture, being oriented mostly parallel to bone surface, and (v) local surface curvature seems to have an effect on the ultrastructure organization. Further studies that investigate bone ultrastructure orientation and arrangement are needed in order to understand its organization and consequently its relation to bone biology and mechanics. PMID:27547973

A phase II, multicentre trial evaluating the efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal-related events.

PubMed

Addison, Christina L; Bouganim, Nathaniel; Hilton, John; Vandermeer, Lisa; Dent, Susan; Amir, Eitan; Hopkins, Sean; Kuchuk, Iryna; Segal, Roanne; Song, Xinni; Gertler, Stan; Mazzarello, Sasha; Dranitsaris, George; Ooi, Daylily; Pond, Gregory; Clemons, Mark

2014-04-01

The optimal frequency of intravenous (IV) bisphosphonate administration is unclear. We thus performed a study evaluating the effects of switching from 3-4 to 12 weekly therapy in patients with biochemically defined low-risk bone metastases. Patients with serum C-telopeptide (CTx) levels ≤600 ng/L after ≥3 months of 3-4 weekly IV pamidronate were switched to 12 weekly therapy for 48 weeks. Primary endpoint was the proportion of patients maintaining CTx levels in the lower-risk range. All endpoints (serum CTx and bone-specific alkaline phosphatase (BSAP), skeletal-related events (SREs) and self-reported pain) were measured at baseline, 6, 12, 24, 36 and 48 weeks. Treatment failure was defined as biochemical failure (CTx > 600 ng/L) or a SRE. Exploratory biomarkers including; serum TGF-β, activin-A, bone sialoprotein (BSP), procollagen type 1 N-terminal propeptide and urinary N-telopeptide (NTx) were assessed at baseline as predictors for failure to complete treatment. Seventy-one patients accrued and 43 (61 %) completed 48 weeks of de-escalated therapy. Reasons for failure to complete treatment included; biochemical failure (CTx > 600 ng/L) (n = 10, 14.1 %), on-study SRE (n = 9, 12.7 %), disease progression (n = 7, 9.9 % including death from disease [n = 1, 1.4 %]) or patient choice (n = 2, 2.8 %). Elevated baseline levels of CTx, BSAP, NTx and BSP were associated with treatment failure. The majority of patients in this biochemically defined low-risk population could switch from 3-4 weekly to 12 weekly bisphosphonate therapy with no effect on CTx levels or SREs during the 48 week study. Larger trials are required to assess the roles of biomarkers as predictors of adequacy of de-escalated therapy.

Systemic irradiation for selected stage IV and recurrent pediatric solid tumors: method, toxicity, and preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wharam, M.D.; Kaizer, H.; Leventhal, B.G.

1980-02-01

Eight patients with advanced pediatric solid tumors received either sequential upper and lower half-body irradiation (HBI) (7.5 rad/min to 500 rad total) or total body irradiation (TBI) (7.5 rad/min to 800 rad total) as part of two multimodality treatment regimens. All patients received combination chemotherapy; drugs were determined by the tumor type. The TBI regimen was selected for two patients who had progression of disease with conventional chemotherapy and for two patients with stage IV neuroblastoma. This intensive regimen consisted of bone marrow harvesting, followed by local radiation to gross disease, marrow-ablative chemotherapy, TBI, and re-infusion of the cryopreserved autologousmore » marrow. Significant acute toxicity was followed by hematologic reconstitution in each patient within seven weeks. At this writing, two patients survived, one of whom is disease free two and one half years without maintenance chemotherapy. A less intensive, outpatient regimen was selected for four patients; three had a complete or good partial response to chemotherapy. The fourth patient had tumor-involved bone marrow not responsive to chemotherapy and was therefore ineligible for marrow cryopreservation and TBI. Each of these four patients received HBI after chemotherapy and local radiation to the primary and/or metastatic sites. Acute toxicity was limited to nausea and vomiting. Significant leukopenia and thrombocytopenia occurred in three patients. All four patients were alive 10 to 26 months post HBI. This pilot study demonstrates that chemotherapy can be integrated with local fractionated radiation, and systemic radiation given as HBI or TBI with acceptable toxicity; sufficient bone marrow stem cells can be harvested after conventional chemotherapy and then cryopreserved to permit hematologic reconstitution of the patient who receives marrow ablative therapy.« less

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Assessment of the influence of Laser phototherapy on the bone repair process of complete fractures in tibiae of rabbits stabilized with semi-rigid internal fixation treated with or without MTA graft: a histological study

NASA Astrophysics Data System (ADS)

Soares, Luiz G. P.; Silva, Aline C. P.; Silva, Anna Paula L. T.; Neves, Bruno Luiz R. C.; Santos, Nicole R. S.; dos Santos, Jean N.; Pinheiro, Antonio L. B.

2016-03-01

Beside biomaterials, Laser phototherapy has shown positive effects as auxiliary therapy in bone repair process, especially when involving large bone losses. The aim of this histological study was to evaluate, by light microscopy, the influence of laser phototherapy on the repair of complete tibial fractures in rabbits treated or not with semi-rigid internal fixation and Mineral Trioxide Aggregate - MTA graft. Twelve Rabbits were randomly divided into four groups with three animals each. After general anesthesia, complete fractures were created in one tibia with a carborundum disk. All animals (groups I-IV) had the fracture stabilized with semi-rigid fixation (wire osteosynthesis - WO). Group I was routinely fixed with WO; groups II and IV fracture was filled by blood clot and MTA implant. In Groups III and IV fracture was filled by blood clot and further irradiated with laser (λ780 nm, 70 mW, CW, Φ = 0.04 cm2, 20.4 J/cm2, per session, t = 300s, 142.8 J/cm2 per treatment). The phototherapy protocol was applied immediately after the surgery and repeated each 48 hours during 15 days. Animal death occurred on the 30th postoperative day. After removal of the specimens, the samples were routinely processed, stained with HE and evaluated by light microscopy. Histologically, the group treated with MTA graft and irradiated with laser showed the fracture filled by a more organized and mature trabecular bone, when compared with all other groups. From the results of the present study, it may be concluded that the association of Laser phototherapy + MTA graft in fractures treated with WO improved bone repair when compared with fractures treated only with WO.

Bone density and size in ambulatory children with cerebral palsy.

PubMed

Al Wren, Tishya; Lee, David C; Kay, Robert M; Dorey, Frederick J; Gilsanz, Vicente

2011-02-01

To examine the relation of axial and appendicular bone properties in ambulatory children with cerebral palsy (CP) to functional (Gross Motor Function Classification System [GMFCS]) level. Quantitative computed tomography measurements were compared among 37 children with CP (12 children in GMFCS level I, five in level II, 18 in level III, two in level IV; five with hemiplegia, 23 with diplegia, two with triplegia, seven with quadriplegia; mean age 9y 4mo, SD 1y 6mo; 18 males, 19 females) and 37 children in a comparison group (same age and sex distributions). Linear regression was used to evaluate differences in volumetric cancellous bone density (vBMD) and geometric properties of the L3 vertebra and tibia, adjusting for height, weight, and sex as covariates. The comparison group had larger vertebrae than the children with CP (p = 0.02) owing to smaller vertebral size in GMFCS levels III and IV, but there was no difference in vertebral vBMD (p = 0.49). In the tibia, bone volumetric density (p = 0.09) and size (p = 0.02) decreased with increasing GMFCS level. GMFCS level had a greater effect on bone size in females than in males (p<0.07). Children with CP of all levels may have less bone in their tibias, whereas spine deficits differentially affect more involved children. Because even small bone deficits may manifest as osteoporosis later in life, it is important to study bone acquisition in all children with CP. © The Authors. Journal compilation © Mac Keith Press 2010.

Acute haematogenous community-acquired methicillin-resistant Staphylococcus aureus osteomyelitis in an adult: Case report and review of literature

PubMed Central

2012-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) has of late emerged as a cause of community-acquired infections among immunocompetent adults without risk factors. Skin and soft tissue infections represent the majority of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clinical presentations, whilst invasive and life-threatening illness like necrotizing pneumonia, necrotizing fasciitis, pyomyositis, osteomyelitis and sepsis syndrome are less common. Although more widely described in the pediatric age group, the occurrence of CA-MRSA osteomyelitis in adults is an uncommonly reported entity. Case presentation We describe an invasive CA-MRSA infection in a 28 year-old previously healthy male, manifesting with bacteraemia, osteomyelitis of femur, pyomyositis and septic arthritis of the knee. Initially a preliminary diagnosis of osteosarcoma was suggested by imaging studies and patient underwent a bone biopsy. MRSA was subsequently isolated from blood cultures taken on day of admission, bone, tissue and pus cultures. Incision and drainage of abscess was performed and patient was treated with vancomycin, with fusidic acid added later. It took 6 months for the inflammatory markers to normalize, warranting 6-months of anti-MRSA therapy. Patient was a fervent deer hunter and we speculate that he acquired this infection from extensive direct contact with deer. Molecular characterization of this isolate showed that it belonged to multilocus sequence type (MLST) ST30 and exhibited the staphylococcal chromosome cassette mec (SCCmec) type IV, staphylococcus protein A (spa) type t019, accessory gene regulator (agr) type III and dru type dt10m. This strain harbored Panton-Valentine leukocidin (pvl) genes together with 3 other virulent genes; sei (enterotoxin), hlg (hemolysin) and fnbA (fibronectin binding protein). Conclusion This case study alerts physicians that beyond the most commonly encountered skin and soft tissue infections, pvl positive CA-MRSA can lead to invasive life-threatening disease especially in an immunocompetent adult. Heightened alertness is needed for osteomyelitis of long bones in adults, as it is not uncommon for this disease to mimic primary bone malignancy. Cure is achievable with early appropriate antibiotics guided by inflammatory markers. PMID:23098162

Acute haematogenous community-acquired methicillin-resistant Staphylococcus aureus osteomyelitis in an adult: case report and review of literature.

PubMed

Dhanoa, Amreeta; Singh, Vivek Ajit; Mansor, Azura; Yusof, Mohd Yasim; Lim, King-Ting; Thong, Kwai-Lin

2012-10-25

Methicillin-resistant Staphylococcus aureus (MRSA) has of late emerged as a cause of community-acquired infections among immunocompetent adults without risk factors. Skin and soft tissue infections represent the majority of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clinical presentations, whilst invasive and life-threatening illness like necrotizing pneumonia, necrotizing fasciitis, pyomyositis, osteomyelitis and sepsis syndrome are less common. Although more widely described in the pediatric age group, the occurrence of CA-MRSA osteomyelitis in adults is an uncommonly reported entity. We describe an invasive CA-MRSA infection in a 28 year-old previously healthy male, manifesting with bacteraemia, osteomyelitis of femur, pyomyositis and septic arthritis of the knee. Initially a preliminary diagnosis of osteosarcoma was suggested by imaging studies and patient underwent a bone biopsy. MRSA was subsequently isolated from blood cultures taken on day of admission, bone, tissue and pus cultures. Incision and drainage of abscess was performed and patient was treated with vancomycin, with fusidic acid added later. It took 6 months for the inflammatory markers to normalize, warranting 6-months of anti-MRSA therapy. Patient was a fervent deer hunter and we speculate that he acquired this infection from extensive direct contact with deer.Molecular characterization of this isolate showed that it belonged to multilocus sequence type (MLST) ST30 and exhibited the staphylococcal chromosome cassette mec (SCCmec) type IV, staphylococcus protein A (spa) type t019, accessory gene regulator (agr) type III and dru type dt10m. This strain harbored Panton-Valentine leukocidin (pvl) genes together with 3 other virulent genes; sei (enterotoxin), hlg (hemolysin) and fnbA (fibronectin binding protein). This case study alerts physicians that beyond the most commonly encountered skin and soft tissue infections, pvl positive CA-MRSA can lead to invasive life-threatening disease especially in an immunocompetent adult. Heightened alertness is needed for osteomyelitis of long bones in adults, as it is not uncommon for this disease to mimic primary bone malignancy. Cure is achievable with early appropriate antibiotics guided by inflammatory markers.

Evaluation of lipid peroxidation and antioxidant defense mechanisms in the bone of rats in conditions of separate and combined administration of vanadium (V) and magnesium (Mg).

PubMed

Ścibior, Agnieszka; Gołębiowska, Dorota; Adamczyk, Agnieszka; Kurus, Joanna; Staniszewska, Magdalena; Sadok, Ilona

2018-03-25

The impact of vanadium (V) and magnesium (Mg) applied as sodium metavanadate (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on oxidative stress markers in bone of male Wistar rats was investigated. Some of them were also measured in the liver, e.g. l-ascorbic acid (hepatic L-AA). Additionally, relationships between selected indices determined in bone were examined. SMV alone (Group II) did not significantly alter the level of TBARS and the activity of SOD, compared with the control (Group I), but it slightly reduced the GR activity (by 13%) and the L-AA level (by 15.5%). It also markedly lowered the activity of CAT and GPx (by 34% and 29%), and to some degree elevated the activity of GST (by 16%) and the hepatic L-AA level (by 119%). MS alone (Group III) decreased the TBARS level (by 49%), slightly lowered the L-AA concentration (by 14%), and reduced the SOD, GPx, and GR activities (by 31%, 40%, and 28%), but did not change the activity of CAT, compared with the control. Additionally, it elevated the GST activity (by 56%) and the hepatic L-AA level (by 40%). In turn, the SMV + MS combination (Group IV) reduced the TBARS level (by 38%) and the SOD, CAT, GPx, and GR activities (by 61%, 58%, 72%, and 40%) but elevated the GST activity (by 66%), compared with the control. The activity of SOD and GPx in the rats in Group IV was also reduced, compared with Group II (by 61% and 61%) and Group III (by 44% and 54%). In turn, the activities of CAT and GR were decreased, compared with Group III (by 55%) and Group II (by 31%), and the L-AA level was lowered, in comparison with Groups II and III (by 53% and 54%). Further, the concentration of V in the bone of rats in Groups II and IV increased, whereas the concentration of Mg decreased, compared with Groups I and III, in which the V and Mg levels dropped and were not altered, respectively, compared with Group I. The total content of Fe in the bone of rats in Groups II and IV increased, compared with Group III, in which the total Fe content did not change, compared with Group I. In turn, the total bone Cu content significantly decreased in the rats in Groups III and IV, compared with Groups I and II, whereas the total Zn content and the Ca concentration did not change markedly. The results provided evidence that the concentration of V used as SMV did not enhance LPO in bone, whereas Mg, at the selected level, markedly reduced LPO in this tissue. On the other hand, both elements administered separately and in combination disrupted the antioxidant defense mechanisms and homeostasis of some metals in bone tissue, which consequently may have contributed to disturbances in the balance in the activities of osteoblastic and osteoclastic cells, and thereby negatively affected bone health. Copyright © 2018 Elsevier B.V. All rights reserved.

[APPLICATION AND EFFECTIVENESS OF BIOLOGICAL TYPE ACETABULAR CUP IN ADULT Crowe TYPE IV DEVELOPMENTAL DYSPLASIA OF THE HIP].

PubMed

Xu, Ning; Sun, Junying; Zhao, Xijiang; Wang, Tao

2016-01-01

To investigate the application and effectiveness of the biological type acetabular cup(diameter < 44 mm) in adult Crowe type IV developmental dysplasia of the hip (DDH). Between April 2001 andAugust 2013, biological type acetabular cup was used in total hip arthroplasty for the treatment of Crowe type IV DDH in16 cases (20 hips). There were 3 males and 13 females, aged 31-69 years (mean, 49 years). Unilateral hip was involved in 12cases, and bilateral hips in 4 cases. The patients showed pain of the hip joint and inequality of lower limb (shortening ofaffected limb 1.8-6.0 cm in length, 3.5 cm on average). Acetabular deformity, the relationship and the severity of femoralhead dislocation were comfirmed on the X-ray films. The preoperative Harris score was 34.0 ± 6.9. All patientsachieved healing of incision by first intention, with no complication of infection or neurovascular injury. Sixteen caseswere followed up 4-12 years (mean, 7.5 years). At 2 weeks after operation, dislocation occurred in 2 cases, and were fixedwith plaster for 3 weeks after reduction of the hip. Postoperative X-ray films showed complete reduction of femoral head;the average acetabular coverage of the cup of the weight-bearing area was 98.5% (range, 98.2%-99.1%). The cup from theRanawat triangle was 4.6-7.0 mm (mean, 5.8 mm) in medial shifting, and was 4.5-7.9 mm (mean, 6.2 mm) in elevation,it located at cup lateral surface area inside the iliopectineal line and the Kohler line (< 40%); the cup abduction angle was(45 ± 5)degrees, and the anteversion angle was (10 ± 5)degrees. The other patients had no prosthesis loosening except 1 patient havingextensive acetabular prosthesis loosening because of acetabular osteolysis at 12 years after operation. The hip Harris scorewas significantly improved to 85.0 ± 7.5 at 1 year after operation (t = 14.34, P = 0.01). The acetabular grindingprocess to retain enough bone combined with a small cup of-biological prosthesis treating adult Crowe type IV DDH has theadvantages of satisfactory coverage and initial acetabular fixation, so good early and mid-term effectiveness can be obtained.

Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

PubMed

Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

2016-07-01

Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment maintenance regimens should be considered on a case-by-case basis. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Therapies for the bone in mucopolysaccharidoses

PubMed Central

Tomatsu, Shunji; Alméciga-Díaz, Carlos J.; Montaño, Adriana M.; Yabe, Hiromasa; Tanaka, Akemi; Dung, Vu Chi; Giugliani, Roberto; Kubaski, Francyne; Mason, Robert W.; Yasuda, Eriko; Sawamoto, Kazuki; Mackenzie, William; Suzuki, Yasuyuki; Orii, Kenji E.; Barrera, Luis A.; Sly, William S.; Orii, Tadao

2014-01-01

Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required. Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life. This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs. PMID:25537451

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta.

PubMed

Little, David G; Peacock, Lauren; Mikulec, Kathy; Kneissel, Michaela; Kramer, Ina; Cheng, Tegan L; Schindeler, Aaron; Munns, Craig

2017-08-01

In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Pioglitazone-induced bone loss in diabetic rats and its amelioration by berberine: A portrait of molecular crosstalk.

PubMed

Adil, Mohammad; Mansoori, Mohd Nizam; Singh, Divya; Kandhare, Amit Dattatraya; Sharma, Manju

2017-10-01

Diabetes mellitus and osteoporosis both are high prevalence disorders, especially in the elderly population. Pioglitazone, a PPAR-γ agonist associated with bone loss and risk of fracture in type 2 diabetes mellitus patients. In this study, ameliorative effect of berberine against pioglitazone-induced bone loss in diabetic rats and possible mechanisms has been explored. Diabetes was induced in male Wistar albino rats by streptozotocin (65 mg/kg, i.v.) after 15min of nicotinamide (230mg/kg, i.p.) administration. Diabetic rats were treated orally with pioglitazone (10mg/kg) and berberine (100mg/kg) alone and in combination of both for 12 weeks. Femur of each rat was isolated and evaluated for the bone micro-architecture, BMD, histology and mRNA expression of PPAR-γ, AMPK, and bone turnover markers (RANKL, OPG, Runx2, and osteocalcin). Urinary calcium and serum TRAP was also measured. Treatment of pioglitazone and berberine alone and in combination significantly ameliorate abnormal blood glucose, serum insulin, and HbA1c levels in streptozotocin-induced diabetic rats. Pioglitazone treatment significantly increased urinary calcium, serum TRAP, mRNA expression of RANKL, PPAR-γ as well as significantly decreased Runx2, OPG, osteocalcin and AMPK levels in diabetic rats. Pioglitazone administration also shows detrimental effect on femur epiphysis micro-architecture, BMD and histology. Whereas, berberine treatment alone and in combination with pioglitazone remarkably ameliorates the abnormal urinary calcium, mRNA expression of AMPK, bone turnover markers, femur epiphysis micro-architecture, histology and also increases BMD in diabetic rats. In conclusion, berberine shows protective effect against pioglitazone-induced bone loss in diabetic rats possibly through AMPK activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Manipulative reduction and external fixation with cardboard splint for the treatment of calcaneal fractures: a 60-case report].

PubMed

Hao, Bo-Chuan; Xie, Ke-Bo

2014-07-01

To investigate the therapeutic effects of manipulative reduction for calcaneal fractures. From January 2009 to June 2012, 53 cases (60 affected feet) of Sanders type I-IV calcaneal fractures were treated by manipulative reduction and external fixation with cardboard splint,including 45 males and 8 females with an average age of (33.5 +/- 1.54) years old ranging from 18 to 65. The course of disease ranged 0.5 h to 7 d. Before treatment the feet were swelling, ache and activity limitation in evidence, some feet were wide flat deformity, the cortical bone was broken in the imaging examination. All selected cases were evaluated using Creighton-Nebraska health foundation assessment scale for fractures of calcaneus. All cases were followed up at 12 months after treatment, 13 feet got excellent curative effect, 34 good, 11 moderate and 2 poor. Manipulative reduction for Sanders type I-IV calcaneal fractures could get excellent curative effect. Manipulative reduction for calcaneal fractures could avoid surgical trauma while assure high curative effects. Manipulative reduction is not only economical and easy therapy, but also can restore maximum function of the calcaneus with few complications and facilitate early rehabilitation of ankle and joint function.

Defect nonunion of a metatarsal bone fracture in a cow: successful management with bone plating and autogenous cancellous bone graft.

PubMed

Raghunath, M; Singh, N; Singh, T; Gopinathan, A; Mohindroo, J; Atri, K

2013-01-01

A two-and-half-year-old cow was presented with a defect nonunion of the right metatarsal III/IV bone following a severely comminuted open fracture two months previously. The animal underwent open fixation using a 4.5 mm, broad, 10-hole, dynamic compression plate and autogenous cancellous bone graft collected from the contralateral iliac shaft. The animal started partial weight bearing after the third postoperative day and resumed complete weight bearing after the 10th day. Fracture healing was complete and the implants were removed after the 120th postoperative day. Stable fixation by means of a bone plate in conjunction with a cancellous bone graft facilitated complete healing and restoration of the bone column of the defect and the metatarsal fracture. The animal made a complete recovery.

[Biomaterials for bone filling: comparisons between autograft, hydroxyapatite and one highly purified bovine xenograft].

PubMed

Chappard, D; Zhioua, A; Grizon, F; Basle, M F; Rebel, A

1993-12-01

Bone grafts are becoming increasingly common in orthopaedics, neurosurgery and periodontology. Twenty one New Zealand rabbits were used in the present study comparing several materials usable as bone substitutes. A 4.5 mm hole was drilled in the inner femoral condyles. Holes were filled with either an autograft (from the opposite condyle), an hydroxylapatite (Bioapatite), or a highly purified bovine xenograft (T650 Lubboc). Animals were sacrificed at 1, 3 and 6 months post implantation and a quantitative analysis of newly-formed bone volume (BNF/IV) and remaining biomaterials (BMAT/IV) was done. In addition, some holes were left unfilled and served as controls. At 6 months, there was no tendency for spontaneous repair in the control animals. The autografted animals have repaired their trabecular mass and architecture within the first month. Hydroxylapatite appeared unresorbed at six months and only thin and scanty new trabeculae were observed. The xenograft induced woven bone trabeculae formation on the first month. This was associated with resorption of the material by two multinucleated cell populations. At six months, the epiphyseal architecture was restored and the biomaterial has disappeared in most cases. Xenografts appear a promising alternative to autografts and allografts, whose infectious risks and ethical problems should always be borne in mind.

Polarized type 2 alloreactive CD4+ and CD8+ donor T cells fail to induce experimental acute graft-versus-host disease.

PubMed

Krenger, W; Snyder, K M; Byon, J C; Falzarano, G; Ferrara, J L

1995-07-15

Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a type 1 cytokine phenotype. To prevent the development of acute GVHD, we have successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then transplanted with T cell-depleted bone marrow cells into irradiated recipients across either MHC class II (bm12-->C57BL/6) or class I (bm1-->C57BL/6) barriers, and the intensity of GVHD was measured by assessment of several in vitro and in vivo parameters. The injection of polarized type 2 T cells abrogated the mitogen-induced production of IFN-gamma by splenocytes from transplanted hosts on day 13 after bone marrow transplantation (BMT). Injection of polarized type 2 T cells failed to induce secretion of the effector phase cytokine TNF-alpha by splenocytes stimulated with LPS both in vitro and in vivo, and survival of transplanted mice after i.v. injection with LPS was significantly improved. Furthermore, cell-mixing experiments revealed that polarized type 2 T cells were able to inhibit type 1 cytokine responses induced by naive T cells after BMT. These data demonstrate that both polarized CD4+ and CD8+ type 2 alloreactive donor T cells can be generated in vitro from mature T cell populations. These cells function in vivo to inhibit type 1 T cell responses, and such inhibition attenuates the systemic morbidity of GVHD after BMT across both MHC class II or class I barriers in mice.

Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.

PubMed

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Huang, Yihe; Ma, Yan; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-06-01

The Col1a2(+/G610C) knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2(+/G610C) and their wild-type controls (Col1a2(+/+)), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2(+/G610C) with an LRP(+/A214V) high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2(+/G610C) tibias had 13% fewer secondary trabeculae than Col1a2(+/+), these were thinner (11%) and more widely spaced (20%) than those of Col1a2(+/+) mice. Vertebrae of Col1a2(+/G610C) mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1(a2+/+). The cortical bone of Col1a2(+/G610C) tibias at 2-months had 3% higher tissue mineral density compared to Col1a2(+/+); Col1a2(+/G610C) vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2(+/+). FTIRI analysis, which provides information on bone chemical composition at ~7μm-spatial resolution, showed tibias at 10-days did not differ between genotypes. Comparing identical bone types in Col1a2(+/G610C) to Col1a2(+/+) at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2(+/G610C) vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution was noted in 10-day-old trabecular bone in vertebrae (31%) and in 2-month old trabecular bone in both tibia (31%) and vertebrae (4%). There was also a 16% lower carbonate-to-phosphate ratio in vertebral trabeculae and a correspondingly higher (22%) carbonate-to-phosphate ratio in 2month-old vertebral cortices. At age 3-months-of-age, male femurs with both a Col1a2(+/G610C) allele and a Lrp5 high bone mass allele (Lrp5+/A214V) showed an improvement in bone composition, presenting higher trabecular carbonate-to-phosphate ratio (18%) and lower trabecular and cortical acid-phosphate substitutions (8% and 18%, respectively). Together, these results indicate that mutant collagen α2(I) chain affects both bone quantity and composition, and the usefulness of this model for studies of potential OI therapies such as anti-sclerostin treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone Mineral Properties in Growing Col1a2+/G610C Mice, an animal model of Osteogenesis Imperfecta

PubMed Central

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Yihe, Huang; Yan, Ma; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-01-01

The Col1a2+/G610C knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2+/G610C and their wild-type controls (Col1a2+/+), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2+/G610C with an LRP+/A214V high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2+/G610C tibias had 13% fewer secondary trabeculae than Col1a2+/+, these were thinner (11%) and more widely spaced (20%) than those of Col1a2+/+ mice. Vertebrae of Col1a2+/G610C mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1a2+/+. The cortical bone of Col1a2+/G610C tibias at 2-months had 3% higher tissue mineral density compared to Col1a2+/+; Col1a2+/G610C vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2+/+. FTIRI analysis, which provides information on bone chemical composition at ~ 7 µm-spatial resolution, showed tibias at 10-days, did not differ between genotypes. Comparing identical bone types in Col1a2+/G610C to Col1a2+/+ at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2+/G610C vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution was noted in 10-day-old trabecular bone in vertebrae (31%) and in 2-month old trabecular bone in both tibia (31%) and vertebrae (4%). There was also a 16% lower carbonate-to-phosphate ratio in vertebral trabeculae and a correspondingly higher (22%) carbonate-to-phosphate ratio in 2 month-old vertebral cortices. At age 3- months-of-age, male femurs with both a Col1a2+/G610C allele and a Lrp5 high bone mass allele (Lrp5+/A214V) showed an improvement in bone composition, presenting higher trabecular carbonate-to-phosphate ratio (18%) and lower trabecular and cortical acid-phosphate substitutions (8% and 18%, respectively). Together, these results indicate that mutant collagen α2(I) chain affects both bone quantity and composition, and the usefulness of this model for studies of potential OI therapies such as anti-sclerostin treatments. PMID:27083399

[Operative treatment for complex tibial plateau fractures].

PubMed

Song, Qi-Zhi; Li, Tao

2012-03-01

To explore the surgical methods and clinical evaluation of complex tibial plateau fractures resulted from high-energy injuries. From March 2006 to May 2009,48 cases with complex tibial plateau fractures were treated with open reduction and plate fixation, including 37 males and 11 females, with an average age of 37 years (ranged from 18 to 63 years). According to Schatzker classification, 16 cases were type IV, 20 cases type V and 12 cases type VI. All patients were examined by X-ray flim and CT scan. The function of knee joint were evaluated according to postoperative follow-up X-ray and Knee Merchant Rating. Forty-eight patients were followed up with a mean time of 14 months. According to Knee Merchant Rating, 24 cases got excellent results, 16 cases good, 6 cases fair and 2 cases poor. Appropriate operation time, anatomical reduction, suitable bone graft and reasonable rehabilitation exercises can maximally recovery the function of knee joint.

[Case-control study on bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle joint].

PubMed

Qi, Yue-Feng; Chen, Fa-Lin; Bao, Shu-Ren; Li, Cheng-Huan; Zhao, Xing-Wei; Liu, Shi-Ming; Chen, Wen-Xue; Li, Ye; Wang, Peng

2012-08-01

To explore therapeutic effects of bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle,and analyze manipulative reduction mechanism. From 2005 to 2008, 95 patients with over degree II supination-eversion fractures of ankle were treated respectively by manipulation and operation. There were 43 cases [11 males and 32 females with an average age of (44.95 +/- 12.65) years] in manipulation group, and 2 cases were degree II, 11 cases were degree III, and 30 cases were degree IV. There were 52 cases [21 males and 31 females with an average age of (39.96 +/- 13.28) years] in operative group,and 6 cases were degree II, 18 cases were degree III, and 28 cases were degree IV. Bone setting manipulation and hard splint external fixation were applied to manipulative group. Operative reduction internal fixation was performed in operative group. X-ray was used to evaluate reduction of fracture before and after treatment, 2 months after treatment. Ankle joint function was evaluated according to Olerud-Molander scoring system after 6 months treatment. All patients were followed up with good reduction. Three cases occurred wound complication in operative group, but not in manipulative group. In manipulation group, 19 cases got excellent results, 20 cases good and 4 cases fair; while in operative group, 30 cases got excellent results, 20 cases good and 2 cases poor. There were no significant differences in fracture reduction and ankle joint function recovery between two groups (P > 0.05). Efficacy of operative treatment was better than that of manipulative treatment at degree IV fracture (P < 0.05). Bone setting manipulation is a good method for treating supination-eversion ankle joint fractures, which has advantages of simple and safe operation, reliable efficacy. For ankle join fracture at degree IV, manipulative reduction should be adopted earlier, and operative treatment also necessary

Sandwich allografts for long-bone nonunions in patients with osteogenesis imperfecta: a retrospective study.

PubMed

Puvanesarajah, Varun; Shapiro, Jay R; Sponseller, Paul D

2015-02-18

Patients with osteogenesis imperfecta often develop nonunions, as internal fixation has limited applicability in this condition. We report the outcomes of a modified "sandwich technique" in the treatment of long-bone nonunions in patients with osteogenesis imperfecta; this technique brings circumferential stabilization and normal collagen to the nonunion site. From May 2003 through February 2012, twelve patients (eight females, four males; median age, 39.0 years; range, eleven to seventy-eight years) who had osteogenesis imperfecta (Sillence type I [three], type III [eight], and type IV [one]) and a combined total of thirteen nonunions (two humeral, two radial, three femoral, four tibial, and two ulnar; median duration, 15.0 months; range, six to 204 months) were treated at our institution with compressed sandwich allograft cortical struts. The struts were fashioned to be wide enough to allow for increased osteoconductive surface area and to approximate a hemicylindrical shape. Treatment history and demographics data were acquired through retrospective chart review. Follow-up radiographs were analyzed by two attending orthopaedic surgeons to determine radiographic findings. The median follow-up time was 4.6 years (range, 2.1 to 10.3 years). All thirteen nonunions, including one requiring a second graft procedure, healed with abundant, smooth allograft incorporation, resulting in an initial healing rate of 92% because of a refracture in one patient. This patient's nonunion ultimately healed with additional allograft struts and a new intramedullary rod. One patient required removal of prominent screws. The final follow-up examinations revealed no pain or refracture at the original nonunion site. All patients regained their prefracture level of function. Sandwich allograft struts constitute a durable, safe method for the stabilization and healing of persistent long-bone nonunions in patients with osteogenesis imperfecta. All patients showed incorporation of the allograft to the native diaphysis. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Operative Treatment of Fifth Metatarsal Jones Fractures (Zones II and III) in the NBA.

PubMed

O'Malley, Martin; DeSandis, Bridget; Allen, Answorth; Levitsky, Matthew; O'Malley, Quinn; Williams, Riley

2016-05-01

Proximal fractures of the fifth metatarsal (zone II and III) are common in the elite athlete and can be difficult to treat because of a tendency toward delayed union, nonunion, or refracture. The purpose of this case series was to report our experience in treating 10 NBA players, determine the healing rate, return to play, refracture rate, and role of foot type in these athletes. The records of 10 professional basketball players were retrospectively reviewed. Seven athletes underwent standard percutaneous internal fixation with bone marrow aspirate concentrate (BMAC) whereas the other 3 had open bone grafting primarily in addition to fixation and BMAC. Radiographic features evaluated included fourth-fifth intermetatarsal, fifth metatarsal lateral deviation, calcaneal pitch, and metatarsus adductus angles. Radiographic healing was observed at an overall average of 7.5 weeks and return to play was 9.8 weeks. Three athletes experienced refractures. There were no significant differences in clinical features or radiographic measurements except that the refracture group had the highest metatatarsus adductus angles. Most athletes were pes planus and 9 of 10 had a bony prominence under the fifth metatarsal styloid. This is the largest published series of operatively treated professional basketball players who exemplify a specific patient population at high risk for fifth metatarsal fracture. These players were large and possessed a unique foot type that seemed to be associated with increased risk of fifth metatarsal fracture and refracture. This foot type had forefoot metatarsus adductus and a fifth metatarsal that was curved with a prominent base. We continue to use standard internal fixation with bone marrow aspirate but advocate additional prophylactic open bone grafting in patients with high fourth-to-fifth intermetatarsal, fifth metatarsal lateral deviation, and metatarsus adductus angles as well as prominent fifth metatarsal styloids in order to improve fracture healing and potentially decrease the risk of refracture. Level IV, case series. © The Author(s) 2016.

Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

PubMed

Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

2007-10-01

Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

Allergies in orthopaedic and trauma surgery.

PubMed

Lohmann, C H; Hameister, R; Singh, G

2017-02-01

Hypersensitivity reactions to implants in orthopaedic and trauma surgery are a rare but devastating complication. They are considered as a delayed-type of hypersensitivity reaction (type IV), characterized by an antigen activation of sensitized T-lymphocytes releasing various cytokines and may result in osteoclast activation and bone resorption. Potential haptens are originated from metal alloys or bone-cement. A meta-analysis has confirmed a higher probability of developing a metal hypersensitivity postoperatively and noted a greater risk of failed replacements compared to stable implants. Hypersensitivity to implants may present with a variety of symptoms such as pain, joint effusion, delayed wound/bone healing, persistent secretion, allergic dermatitis (localized or systemic), clicking noises, loss of joint function, instability and failure of the implant. Various diagnostic options have been offered, including patch testing, metal alloy patch testing, histology, lymphocyte transformation test (LTT), memory lymphocyte immunostimulation assay (MELISA), leukocyte migration inhibition test (LIF) and lymphocyte activation test (LAT). No significant differences between in vivo and in vitro methods have been found. Due to unconvincing evidence for screening methods, predictive tests are not recommended for routine performance. Infectious aetiology always needs to be excluded. As there is a lack of evidence on large-scale studies with regards to the optimal treatment option, management currently relies on individual case-by-case decisions. Several options for patients with (suspected) metal-related hypersensitivity exist and may include materials based on ceramic, titanium or oxinium or modified surfaces. Promising results have been reported, but long-term experience is lacking. More large-scaled studies are needed in this context. In patients with bone-cement hypersensitivity, the component suspected for hypersensitivity should be avoided. The development of (predictive) biomarkers is considered as a major contribution for the future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluation of Anterior Vertebral Interbody Fusion Using Osteogenic Mesenchymal Stem Cells Transplanted in Collagen Sponge.

PubMed

Yang, Wencheng; Dong, Youhai; Hong, Yang; Guang, Qian; Chen, Xujun

2016-05-01

The study used a rabbit model to achieve anterior vertebral interbody fusion using osteogenic mesenchymal stem cells (OMSCs) transplanted in collagen sponge. We investigated the effectiveness of graft material for anterior vertebral interbody fusion using a rabbit model by examining the OMSCs transplanted in collagen sponge. Anterior vertebral interbody fusion is commonly performed. Although autogenous bone graft remains the gold-standard fusion material, it requires a separate surgical procedure and is associated with significant short-term and long-term morbidity. Recently, mesenchymal stem cells from bone marrow have been studied in various fields, including posterolateral spinal fusion. Thus, we hypothesized that cultured OMSCs transplanted in porous collagen sponge could be used successfully even in anterior vertebral interbody fusion. Forty mature male White Zealand rabbits (weight, 3.5-4.5 kg) were randomly allocated to receive one of the following graft materials: porous collagen sponge plus cultured OMSCs (group I); porous collagen sponge alone (group II); autogenous bone graft (group III); and nothing (group IV). All animals underwent anterior vertebral interbody fusion at the L4/L5 level. The lumbar spine was harvested en bloc, and the new bone formation and spinal fusion was evaluated using radiographic analysis, microcomputed tomography, manual palpation test, and histologic examination at 8 and 12 weeks after surgery. New bone formation and bony fusion was evident as early as 8 weeks in groups I and III. And there was no statistically significant difference between 8 and 12 weeks. At both time points, by microcomputed tomography and histologic analysis, new bone formation was observed in both groups I and III, fibrous tissue was observed and there was no new bone in both groups II and IV; by manual palpation test, bony fusion was observed in 40% (4/10) of rabbits in group I, 70% (7/10) of rabbits in group III, and 0% (0/10) of rabbits in both groups II and IV. These findings suggest that mesenchymal stem cells that have been cultured with osteogenic differentiation medium and loaded with collagen sponge could induce bone formation and anterior vertebral interbody fusion. And the rabbit model we developed will be useful in evaluating the effects of graft materials for anterior vertebral interbody fusion. Further study is needed to determine the most appropriate carrier for OMSCs and the feasibility in the clinical setting.

A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer.

PubMed

Body, Jean-Jacques; Facon, Thierry; Coleman, Robert E; Lipton, Allan; Geurs, Filip; Fan, Michelle; Holloway, Donna; Peterson, Mark C; Bekker, Pirow J

2006-02-15

Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.

Reconstruction of failed acetabular component in the presence of severe acetabular bone loss: a systematic review.

PubMed

Volpin, A; Konan, S; Biz, C; Tansey, R J; Haddad, F S

2018-04-13

Acetabular revision especially in the presence of severe bone loss is challenging. There is a paucity of literature critiquing contemporary techniques of revision acetabular reconstruction and their outcomes. The purpose of this study was to systematically review the literature and to report clinical outcomes and survival of contemporary acetabular revision arthroplasty techniques (tantalum metal shells, uncemented revision jumbo shells, reinforced cages and rings, oblong shells and custom-made triflange constructs). Full-text papers and those with an abstract in English published from January 2001 to January 2016 were identified through international databases. A total of 50 papers of level IV scientific evidence, comprising 2811 hips in total, fulfilled the inclusion criteria and were included. Overall, patients had improved outcomes irrespective of the technique of reconstruction as documented by postoperative hip scores. Our pooled analysis suggests that oblong cups components had a lower failure rate compared with other different materials considered in this review. Custom-made triflange cups had one of highest failure rates. However, this may reflect the complexity of revisions and severity of bone loss. The most common postoperative complication reported in all groups was dislocation. This review confirms successful acetabular reconstructions using diverse techniques depending on the type of bone loss and highlights key features and outcomes of different techniques. In particular, oblong cups and tantalum shells have successful survivorship.

Management of patients with Paget's disease: a consensus document of the Belgian Bone Club.

PubMed

Devogelaer, J-P; Bergmann, P; Body, J-J; Boutsen, Y; Goemaere, S; Kaufman, J-M; Reginster, J-Y; Rozenberg, S; Boonen, S

2008-08-01

Paget's disease of bone (PDB) is a potentially crippling condition. Pain, fracture, spinal stenosis, nerve entrapment, vascular steal syndrome, secondary osteoarthritis, bone deformity, dental problems, deafness, excessive bleeding during orthopaedic surgery, rare sarcomatous degeneration, and hypercalcaemia constitute complications that may impair the quality of life. The therapeutic approach varies from symptomatic (analgesics, anti-inflammatory drugs) to more specific drugs such as increasingly potent bisphosphonates. Studies such as the PRISM study should in the future help to determine the superiority or not of aggressive treatment over symptomatic treatment in the prevention of complications. Various oral and/or intravenous (i.v.) bisphosphonates have been tested and are currently on the market. The most recently available nitrogen-containing bisphosphonate, i.v. zoledronic acid, is the most potent therapy available for the treatment of PDB. Its therapeutic efficacy, its long-term effect on biologic activity and its good tolerance currently supports its use as a first-line therapeutic option in patients suffering from PDB.

Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts.

PubMed

Komatsu, Yuko; Ibi, Miho; Chosa, Naoyuki; Kyakumoto, Seiko; Kamo, Masaharu; Shibata, Toshiyuki; Sugiyama, Yoshiki; Ishisaki, Akira

2016-07-01

Bisphosphonates (BPs) are analogues of pyrophosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF‑β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF‑β-induced promotion of cell viability, ii) the TGF‑β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF‑β-induced migratory activity of hGFs and iv) the expression level of TGF‑β type I receptor on the surfaces of hGFs, as well as the TGF‑β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF‑β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad‑dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level.

A 1-year randomized, double-blind, placebo-controlled study of intravenous ibandronate on bone loss following renal transplantation.

PubMed

Smerud, K T; Dolgos, S; Olsen, I C; Åsberg, A; Sagedal, S; Reisæter, A V; Midtvedt, K; Pfeffer, P; Ueland, T; Godang, K; Bollerslev, J; Hartmann, A

2012-12-01

The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

PubMed

Thoma, Daniel S; Cha, Jae-Kook; Sapata, Vitor M; Jung, Ronald E; Hüsler, Juerg; Jung, Ui-Won

2017-11-01

To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ustur whole body case 0269: demonstrating effectiveness of i.v. CA-DTPA for Pu.

PubMed

James, A C; Sasser, L B; Stuit, D B; Glover, S E; Carbaugh, E H

2007-01-01

This whole body donation case (USTUR Registrant) involved a single acute inhalation of an acidic Pu(NO3)4 solution in the form of an aerosol 'mist'. Chelation treatment with intravenously (i.v.) Ca-EDTA was initiated on the day of the intake, and continued intermittently over 6 months. After 2.5 y with no further treatment, a course of i.v. Ca-DTPA was administered. A total of 400 measurements of 239+240Pu excreted in urine were recorded; starting on the first day (both before and during the initial Ca-EDTA chelation) and continuing for 37 y. This sampling included all intervals of chelation. In addition, 91 measurements of 239+240Pu-in-feces were recorded over this whole period. The Registrant died about 38 y after the intake, at age 79 y, with extensive carcinomatosis secondary to adenocarcinoma of the prostate gland. At autopsy, all major soft tissue organs were harvested for radiochemical analyses of their 238Pu, 239+240Pu and 241Am content. Also, all types of bone (comprising about half the skeleton) were harvested for radiochemical analyses, as well as samples of skin, subcutaneous fat and muscle. This comprehensive data set has been applied to derive 'chelation-enhanced' transfer rates in the ICRP Publication 67 plutonium biokinetic model, representing the behaviour of blood-borne and tissue-incorporated plutonium during intervals of therapy. The resulting model of the separate effects of i.v. Ca-EDTA and Ca-DTPA chelation shows that the therapy administered in this case succeeded in reducing substantially the long-term burden of plutonium in all body organs, except for the lungs. The calculated reductions in organ content at the time of death are approximately 40% for the liver, 60% for other soft tissues (muscle, skin, glands, etc.), 50% for the kidneys and 50% for the skeleton. Essentially, all of the substantial reduction in skeletal burden occurred in trabecular bone. This modelling exercise demonstrated that 3-y-delayed Ca-DTPA therapy was as effective as promptly administered Ca-EDTA.

USTUR WHOLE BODY CASE 0269: DEMONSTRATING EFFECTIVENESS OF I.V. CA-DTPA FOR PU

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, Anthony C.; Sasser , Lyle B.; Stuit, Dorothy B.

2008-01-28

This whole body donation case (USTUR Registrant) involved a single acute inhalation of an acidic Pu(NO3)4 solution in the form of an aerosol ‘mist.’ Chelation treatment with i.v. Ca-EDTA was initiated on the day of the intake, and continued intermittently over 6 months. After 2½ years with no further treatment, a course of i.v. Ca-DTPA was administered. A total of 400 measurements of 239+240Pu excreted in urine were recorded; starting on the first day (both before and during the initial Ca-EDTA chelation), and continuing for 37 years. This sampling included all intervals of chelation. In addition, 91 measurements of 239+240Pu-in-fecesmore » were recorded over this whole period. The Registrant died about 38 years after the intake, at age 79 y, with extensive carcinomatosis secondary to adenocarcinoma of the prostate gland. At autopsy, all major soft tissue organs were harvested for radiochemical analyses of their 238Pu, 239+240Pu and 241Am content. Also, all types of bone (comprising about half the skeleton) were harvested for radiochemical analyses, as well as samples of skin, subcutaneous fat and muscle. This comprehensive dataset has been applied to derive ‘chelation-enhanced’ transfer rates in the ICRP Publication 67 plutonium biokinetic model, representing the behaviour of blood-borne and tissue-incorporated plutonium during intervals of therapy. The resulting model of the separate effects of i.v. Ca-EDTA and Ca-DTPA chelation shows that the therapy administered in this case succeeded in reducing substantially the long-term burden of plutonium in all body organs, except for the lungs. The calculated reductions in organ content at the time of death are approximately 40% for the liver, 60% for other soft tissues (muscle, skin, glands, etc.), 50% for the kidneys, and 50% for the skeleton. Essentially all of the substantial reduction in skeletal burden occurred in trabecular bone. This modeling exercise demonstrated that 3-y-delayed Ca-DTPA therapy was as effective as promptly administered Ca-EDTA.« less

Overdenture retaining bar stress distribution: a finite-element analysis.

PubMed

Caetano, Conrado Reinoldes; Mesquita, Marcelo Ferraz; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço; Dos Santos, Mateus Bertolini Fernandes

2015-05-01

Evaluate the stress distribution on the peri-implant bone tissue and prosthetic components of bar-clip retaining systems for overdentures presenting different implant inclinations, vertical misfit and framework material. Three-dimensional models of a jaw and an overdenture retained by two implants and a bar-clip attachment were modeled using specific software (SolidWorks 2010). The studied variables were: latero-lateral inclination of one implant (-10°, -5°, 0°, +5°, +10°); vertical misfit on the other implant (50, 100, 200 µm); and framework material (Au type IV, Ag-Pd, Ti cp, Co-Cr). Solid models were imported into mechanical simulation software (ANSYS Workbench 11). All nodes on the bone's external surface were constrained and a displacement was applied to simulate the settling of the framework on the ill-fitted component. Von Mises stress for the prosthetic components and maximum principal stress to the bone tissue were evaluated. The +10° inclination presented the worst biomechanical behavior, promoting the highest stress values on the bar framework and peri-implant bone tissue. The -5° group presented the lowest stress values on the prosthetic components and the lowest stress value on peri-implant bone tissue was observed in -10°. Increased vertical misfit caused an increase on the stress values in all evaluated structures. Stiffer framework materials caused a considerable stress increase in the framework itself, prosthetic screw of the fitted component and peri-implant bone tissue. Inclination of one implant associated with vertical misfit caused a relevant effect on the stress distribution in bar-clip retained overdentures. Different framework materials promoted increased levels of stress in all the evaluated structures.

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

PubMed Central

Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; da Cunha, Sandro Torrentes; Paula, Luis Felipe; Carvalho, Alysson Roncally; de Carvalho, Antonio Carlos Campos; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli dos Santos

2017-01-01

BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice. PMID:28767980

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.

PubMed

Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; Cunha, Sandro Torrentes da; Paula, Luis Felipe; Carvalho, Alysson Roncally; Carvalho, Antonio Carlos Campos de; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli Dos Santos

2017-08-01

Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

Ulcer osteoma and periosteal reactions to chronic leg ulcers.

PubMed

Karasick, D; Schweitzer, M E; Deely, D M

1997-01-01

The purpose of this study was to describe the types of periosteal reaction seen in response to long-standing leg ulcers and to differentiate the types associated with osteomyelitis. Over a 10-year span, we retrospectively evaluated the radiographs of 20 patients with lower leg soft-tissue ulceration and adjacent periosteal bone reaction of the tibia or fibula. Two of us evaluated the location and appearance of periosteal reaction, and one of us evaluated the patients' medical records for evidence of peripheral vascular disease, systemic illnesses, and osteomyelitis. Twelve patients had organized periosteal reactions that resulted in the appearance of ulcer osteoma. None of these patients subsequently developed osteomyelitis. Eight patients had interrupted lamellar nodular periosteal reactions; six of the eight patients had superimposed osteomyelitis. Our study showed two types of periosteal response to chronic leg ulcers: a solid organized type that over time formed an ulcer osteoma and a lamellar nodular type that was often associated with osteomyelitis. Both types of ulcers were seen in patients with peripheral vascular disease, IV drug abuse, sickle cell disease, and neurologic impairment.

[Female stress urinary incontinence. Surgical repair with pubovaginal sling techniques].

PubMed

Escribano Patiño, Gregorio; Hernández Fernández, Carlos; Subirá Ríos, David; Castaño González, Irene; Moralejo Gárate, Mercedes; Martinez Salamanca, Juan Ignacio

2002-11-01

To review the treatment of female stress urinary incontinence by new systems of tension-free urethral sling TVT type (Tension free vaginal tape) or IVS (intravaginal slingplasty), and the bone anchoring trasvaginal sling procedure Infast. We describe the surgical techniques of the various procedures and perform a bibliographic review on the topic. The pubovaginal sling has become the gold standard in the treatment of female stress urinary incontinence, mainly if there is sphincter intrinsic dysfunction. The concept of tension free medium urethra support has been the most important contribution, that questions the classification of incontinence in types I, II and III, because the pubocervical tension free sling can correct all three. Tension free urethral sling techniques have demonstrated to be effective, minimally invasive with a low complication rate, easily reproducible, and with good continence results in the mid-term.

Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study.

PubMed

Pizzoni, S; Sabattini, S; Stefanello, D; Dentini, A; Ferrari, R; Dacasto, M; Giantin, M; Laganga, P; Amati, M; Tortorella, G; Marconato, L

2018-03-01

Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3 cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3 cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT. © 2017 John Wiley & Sons Ltd.

Adverse events among 2408 unrelated donors of peripheral blood stem cells: results of a prospective trial from the National Marrow Donor Program

PubMed Central

Chitphakdithai, Pintip; Miller, John P.; Logan, Brent R.; King, Roberta J.; Rizzo, J. Douglas; Leitman, Susan F.; Anderlini, Paolo; Haagenson, Michael D.; Kurian, Seira; Klein, John P.; Horowitz, Mary M.; Confer, Dennis L.

2009-01-01

Limited data are available describing donor adverse events (AEs) associated with filgrastim mobilized peripheral blood stem cell (PBSC) collections in unrelated volunteers. We report results in 2408 unrelated PBSC donors prospectively evaluated by the National Marrow Donor Program (NMDP) between 1999 and 2004. Female donors had higher rates of AEs, requiring central line placement more often (17% vs 4%, P < .001), experiencing more apheresis-related AEs (20% vs 7%, P < .001), more bone pain (odds ratio [OR] = 1.49), and higher rates of grades II-IV and III-IV CALGB AEs (OR = 2.22 and 2.32). Obese donors experienced more bone pain (obese vs normal, OR = 1.73) and heavy donors had higher rates of CALGB toxicities (> 95 kg vs < 70 kg, OR = 1.49). Six percent of donors experienced grade III-IV CALGB toxicities and 0.6% experienced toxicities that were considered serious and unexpected. Complete recovery is universal, however, and no late AEs attributable to donation have been identified. In conclusion, PBSC collection in unrelated donors is generally safe, but nearly all donors will experience bone pain, 1 in 4 will have significant headache, nausea, or citrate toxicity, and a small percentage will experience serious short-term adverse events. In addition, women and larger donors are at higher risk for donation-related AEs. PMID:19190248

The roles of vascular endothelial growth factor in bone repair and regeneration

PubMed Central

Hu, Kai; Olsen, Bjorn R.

2016-01-01

Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. PMID:27353702

A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.

PubMed

Gao, Jianting; Huang, Guofeng; Liu, Guojun; Liu, Yan; Chen, Qi; Ren, Lei; Chen, Changqing; Ding, Zhenqi

2016-08-01

We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects. © The Author(s) 2016.

The prognostic value of the hawkins sign and diagnostic value of MRI after talar neck fractures.

PubMed

Chen, Hao; Liu, Wenzhou; Deng, Lianfu; Song, Weidong

2014-12-01

The early diagnosis of avascular necrosis of the talus (AVN) and prediction of ankle function for talar fractures are important. The Hawkins sign, as a radiographic predictor, could exclude the possibility of developing ischemic bone necrosis after talar neck fractures, but its relationship with ankle function remains unclear. The purpose of this study was to illustrate the prognostic effect of the Hawkins sign on ankle function after talar neck fractures and to study the value of early MRI in detecting the AVN changes after talus fractures. Cases of talar neck fractures between November 2008 and November 2013 were evaluated. The occurrences of the Hawkins sign and AVN were studied. X-ray imaging was performed at multiple time points from the 4th to the 12th week after the fractures, and MRI examinations were used in the Hawkins sign negative group, with the time span ranging from 1.5 to 12 months. AOFAS scores of the Hawkins sign positive and negative groups were compared during the follow-up. Forty-four cases (48 feet) were evaluated. The occurrence of positive Hawkins sign was 50%, 30%, and 33.3%, the incidence of AVN was 0%, 10%, and 50%, respectively, in type I, type II, and type III and IV talus fractures, respectively. The AOFAS scores showed no statistically significant difference between Hawkins sign positive group and negative group in type I and II fractures. The Hawkins sign positive group had better AOFAS scores than the negative group in type III and IV fractures. However, there was no statistically significant difference between Hawkins sign positive and negative groups when AVN cases were excluded in type III and IV fractures. The Hawkins sign was a reliable predictor excluding the possibility of AVN. It did not have predictive value on the ankle function in low-energy fractures and may predict better ankle function in high-energy fractures. MRI can diagnose AVN during an earlier period, and we believe Hawkins sign negative patients should undergo MRI examinations 12 weeks after the fractures, especially in high-energy traumatic cases. Level III, comparative case series. © The Author(s) 2014.

Hearing aid silicone impression material as a foreign body in the middle ear.

PubMed

Lee, Hyun-Min; Yi, Keun-Ik; Jung, Jae-Hoon; Lee, Il-Woo

We report an extremely rare case of hearing aid silicone impression material as a foreign body in the middle ear. Symptoms of the patient were otorrhea and vertigo after taking of a mold impression on his only hearing ear, and the symptoms mimicked chronic otitis media. A temporal bone CT scan revealed foreign body material in the middle ear and Eustachian tube. An intact canal wall mastoidectomy with a facial recess approach and type IV tympanoplasty was performed to remove the silicone impression material. In addition to the case report, we review the literature regarding impression material foreign bodies. Copyright © 2016 Elsevier Inc. All rights reserved.

Posterosuperior Placement of a Standard-Sized Cup at the True Acetabulum in Acetabular Reconstruction of Developmental Dysplasia of the Hip With High Dislocation.

PubMed

Xu, Jiawei; Xu, Chen; Mao, Yuanqing; Zhang, Jincheng; Li, Huiwu; Zhu, Zhenan

2016-06-01

We sought to evaluate posterosuperior placement of the acetabular component at the true acetabulum during acetabular reconstruction in patients with Crowe type-IV developmental dysplasia of the hip. Using pelvic computed tomography and image processing, we developed a two-dimensional mapping technique to demonstrate the distribution of preoperative three-dimensional cup coverage at the true acetabulum, determined the postoperative location of the acetabular cup, and calculated postoperative three-dimensional coverage for 16 Crowe type-IV dysplastic hips in 14 patients with a mean age of 52 years (33-78 years) who underwent total hip arthroplasty. Mean follow-up was 6.3 years (5.5-7.3 years). On preoperative mapping, the maximum three-dimensional coverage using a 44-mm cup was 87.31% (77.36%-98.14%). Mapping enabled the successful replacement of 16 hips using a mean cup size of 44.13 mm (42-46 mm) with posterosuperior placement of the cup. Early weight-bearing and no prosthesis revision or loosening during follow-up were achieved in all patients. The postoperative two-dimensional coverage on anteroposterior radiographs and three-dimensional coverage were 96.15% (89.49%-100%) and 83.42% (71.81%-98.50%), respectively. This technique may improve long-term implant survival in patients with Crowe-IV developmental dysplasia of the hip undergoing total hip arthroplasty by allowing the use of durable bearings, increasing host bone coverage, ensuring initial stability, and restoring the normal hip center. Copyright © 2015 Elsevier Inc. All rights reserved.

A 15-year review of midface reconstruction after total and subtotal maxillectomy: part I. Algorithm and outcomes.

PubMed

Cordeiro, Peter G; Chen, Constance M

2012-01-01

Reconstruction of complex midfacial defects is best approached with a clear algorithm. The goals of reconstruction are functional and aesthetic. Over a 15-year period (1992 to 2006), a single surgeon (P.G.C.) performed 100 flaps to reconstruct the following midfacial defects: type I, limited maxillectomy (n = 20); type IIA, subtotal maxillectomy with resection of less than 50 percent of the palate (n = 8); type IIB, subtotal maxillectomy with resection of greater than 50 percent of the palate (n = 8); type IIIA, total maxillectomy with preservation of the orbital contents (n = 22); type IIIB, total maxillectomy with orbital exenteration (n = 23); and type IV, orbitomaxillectomy (n = 19). Free flaps were used in 94 cases (94 percent), and pedicled flaps were used in six (6 percent). One hundred flaps were performed in 96 patients (69 males, 72 percent; 27 females, 28 percent); four patients underwent a second flap reconstruction due to recurrent disease (n = 4, 4 percent). Average patient age was 49.2 years (range, 13 to 81 years). Free-flap survival was 100 percent, with one partial flap loss (1 percent). Five patients suffered systemic complications (5.2 percent), and four died within 30 days of hospitalization (4.2 percent). Over 50 percent of patients returned to normal diet and speech. Almost 60 percent were judged to have an excellent aesthetic result. Free-tissue transfer offers the most effective and reliable form of reconstruction for complex maxillectomy defects. Rectus abdominis and radial forearm free flaps in combination with immediate bone grafting or as osteocutaneous flaps consistently provide the best functional and aesthetic results. Therapeutic, IV.

EPIDEMIOLOGICAL STUDY ON LISFRANC INJURIES

PubMed Central

SOBRADO, MARCEL FARACO; SAITO, GUILHERME HONDA; SAKAKI, MARCOS HIDEYO; PONTIN, PEDRO AUGUSTO; SANTOS, ALEXANDRE LEME GODOY DOS; FERNANDES, TÚLIO DINIZ

2017-01-01

ABSTRACT Objective: To analyze the characteristics of patients with Lisfranc injuries and their associated fractures. Methods: This is a retrospective analysis on 42 patients with Lisfranc injuries hospitalized at Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, between 2006 and 2010. Parameters on patient profile, risk factors, fracture characteristics, data on treatment and acute complications were analyzed. Results: Analysis of 42 cases showed that in our sample, men were more affected than women, with a ratio of 4.25:1. The most frequent trauma mechanism was car accident, followed by motorcycle accident. The most frequent type of injury was isolated lesion type B of Quenu and Kuss classification, representing 50% of cases. The most common fracture on the sample was the second metatarsal bone, with 16 cases, followed by cuboid bone fracture. Among the 42 cases, 17% had exposed fractures and 33 patients presented other associated fractures. The mean time elapsed between the trauma and definitive treatment was 6.7 days, while the mean length of hospital stay was 13.8 days. Six patients presented acute postoperative complications. Conclusion: Lisfranc injuries are more common in men undergoing automobile trauma. The prevalence of associated fractures is a frequent finding and the hospital stay may be longstanding.Level of Evidence IV, Case Series. PMID:28642650

Haploidentical Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

ClinicalTrials.gov

2017-04-10

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases.

PubMed

Pepin, Melanie G; Byers, Peter H

2015-12-01

Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended. © 2015 Wiley Periodicals, Inc.

[The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat model of bone cancer pain].

PubMed

Wang, Li-na; Yang, Jian-ping; Ji, Fu-hai; Wang, Xiu-yun; Zuo, Jian-ling; Xu, Qi-nian; Jia, Xiao-ming; Zhou, Jing; Ren, Chun-guang; Li, Wei

2011-05-10

To investigate the role of brain-derived neurotrophic factor (BDNF) in pain facilitation and spinal mechanisms in the rat model of bone cancer pain. The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups (n = 12 each) randomly; group I: control group (sham operation); group II: model group; group III: control group + anti-BDNF intrathecal (i.t.); group IV: model group + control IgG i.t.; group V: model group + anti-BDNF i.t.. Anti-BDNF or control IgG was injected i.t. during 7 to 9th day. Von-Frey threshold was measured one day before operation and every 2 days after operation. On the 9th day after threshold tested, rats were sacrificed after i.t. injection of either anti-BDNF or control IgG, the lumbar 4-6 spinal cord was removed. The expression of the spinal BDNF and the phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) were detected by immunohistochemistry assay and Western-Blot. Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence. We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation, von-Frey threshold in groups II and IV was significantly lower than that in group I and group V (P < 0.01), group V was remarkly higher than that in group IV (P < 0.01). The spinal BDNF and p-ERK1/2 expression in group II or IV were significantly increased compared with that in group I or V (P < 0.01), intrathecal anti-BDNF was significantly suppressed BDNF and p-ERK1/2 expression (P < 0.01). BDNF and p-ERK1/2 was coexistence in the spinal cord of rats, and it maybe involved in the bone cancer pain.

Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

PubMed Central

Cho, Yeona; Chang, Jee Suk; Rha, Koon Ho; Hong, Sung Joon; Choi, Young Deuk; Ham, Won Sik; Kim, Jun Won; Cho, Jaeho

2016-01-01

Purpose/Objectives Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. Materials/Methods The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. Results Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity. Conclusions Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID:26807740

Bone Repair on Fractures Treated with Osteosynthesis, ir Laser, Bone Graft and Guided Bone Regeneration: Histomorfometric Study

NASA Astrophysics Data System (ADS)

dos Santos Aciole, Jouber Mateus; dos Santos Aciole, Gilberth Tadeu; Soares, Luiz Guilherme Pinheiro; Barbosa, Artur Felipe Santos; Santos, Jean Nunes; Pinheiro, Antonio Luiz Barbosa

2011-08-01

The aim of this study was to evaluate, through the analysis of histomorfometric, the repair of complete tibial fracture in rabbits fixed with osteosynthesis, treated or not with infrared laser light (λ780 nm, 50 mW, CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical fractures were created, under general anesthesia (Ketamina 0,4 ml/Kg IP and Xilazina 0,2 ml/Kg IP), on the dorsum of 15 Oryctolagus rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with wire osteosynthesis. Animals of groups III and V were grafted with hydroxyapatite and GBR technique used. Animals of groups IV and V were irradiated at every other day during two weeks (16 J/cm2, 4×4 J/cm2). Observation time was that of 30 days. After animal death (overdose of general anesthetics) the specimes were routinely processed to wax and underwent histological analysis by light microscopy. The histomorfometric analysis showed an increased bone neoformation, increased collagen deposition, less reabsorption and inflammation when laser was associated to the HATCP. It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of CHA.

Pyridinium cross-links in bone of patients with osteogenesis imperfecta: evidence of a normal intrafibrillar collagen packing.

PubMed

Bank, R A; Tekoppele, J M; Janus, G J; Wassen, M H; Pruijs, H E; Van der Sluijs, H A; Sakkers, R J

2000-07-01

The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III, and IV) as well as controls. The amount of triple helical Hyl was increased in all patients. LP levels in OI were not significantly different; in contrast, the amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline level) was significantly increased. There was no relationship between the sum of pyridinolines and the amount of triple helical Hyl, indicating that lysyl hydroxylation of the triple helix and the telopeptides are under separate control. Cross-linking is the result of a specific three-dimensional arrangement of collagens within the fibril; only molecules that are correctly aligned are able to form cross-links. Inasmuch as the total amount of pyridinoline cross-links in OI bone is similar to control bone, the packing geometry of intrafibrillar collagen molecules is not disturbed in OI. Consequently, the brittleness of bone is not caused by a disorganized intrafibrillar collagen packing and/or loss of cross-links. This is an unexpected finding, because mutant collagen molecules with a random distribution within the fibril are expected to result in disruptions of the alignment of neighboring collagen molecules. Pepsin digestion of OI bone revealed that collagen located at the surface of the fibril had lower cross-link levels compared with collagen located at the inside of the fibril, indicating that mutant molecules are not distributed randomly within the fibril but are located preferentially at the surface of the fibril.

The Outcomes of Nonelongating Intramedullary Fixation of the Lower Extremity for Pediatric Osteogenesis Imperfecta Patients: A Meta-analysis.

PubMed

Scollan, Joseph P; Jauregui, Julio J; Jacobsen, Christina M; Abzug, Joshua M

Osteogenesis imperfecta is usually due to autosomal dominant mutations in type I collagen, leading to an increase in fractures and bone deformities, especially in the long bones of the lower extremities. The use of nonelongating intramedullary rods is an established surgical intervention to address such deformities. The rate of surgical complications has been reported to be as high as 187%, with revision rates as high as 90%, although exact global rates are unknown. As such, we sought to determine the published rates of (1) bone-related complications (including both fracture and deformity), (2) rod migration, and (3) complications that require reoperation. Following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines, 1295 studies were evaluated. After cross-referencing, and applying specific inclusion and exclusion criteria, a total of 7 studies were included in the final cohort. Data were extracted from the studies and analyzed. Random effect models determined the complication rates of intramedullary nonelongating rod procedures. A total of 359 primary nonelongating intramedullary rod procedures of tibiae and femurs, in patients with a mean age of 6 years (5.2 to 7.3 y), at a mean follow-up of 63 months (24 to 118 mo), were evaluated. 60% of the surgical procedures were on femurs, and 40% were on tibiae. The reoperation rate was 39.4%. The most common complication was rod migration, with a rate of 25.7%. The rate of bone-related complications was 19.5% including fractures (15.0%) and worsening bone deformity (4.3%). This is the first meta-analysis to identify the rates of complication and reoperation in lower limb intramedullary fixation for pediatric osteogenesis imperfecta patients. This study has shown that rod migration is the most common complication, followed by bone-related complications including fractures and deformity. Reoperations occur after nearly 40% of all procedures due to rod migration or bone-related complications. Level IV-retrospective meta-analysis.

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2016-06-09

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

The AAHKS Clinical Research Award: Intraosseous Regional Prophylaxis Provides Higher Tissue Concentrations in High BMI Patients in Total Knee Arthroplasty: A Randomized Trial.

PubMed

Chin, Seung Joon; Moore, Grant A; Zhang, Mei; Clarke, Henry D; Spangehl, Mark J; Young, Simon W

2018-07-01

Obesity is an established risk factor for periprosthetic joint infections after total knee arthroplasty (TKA). In obese patients, a larger dose of prophylactic vancomycin based on actual body weight is required to reach therapeutic concentrations. It is unclear how tissue concentrations are affected when intraosseous regional administration (IORA) is used in this population. This study compared tissue concentrations of low-dose vancomycin via IORA vs actual body weight-adjusted systemic intravenous (IV) dose in primary TKA. Twenty-two patients with a body mass index (BMI) >35 undergoing TKA were randomized into 2 groups. The IV group received 15 mg/kg (maximum of 2 g) of systemic IV vancomycin and the IORA group received 500 mg vancomycin into the tibia. Subcutaneous fat and bone samples were taken at regular intervals. Tissue antibiotic concentrations were measured using liquid chromatography coupled with tandem mass spectrometry. A blood sample was taken 1 to 2 hours after tourniquet deflation to measure systemic concentration. The mean BMI was 41.1 in the IORA group and 40.1 in the IV systemic group. The overall mean tissue concentration in subcutaneous fat was 39.3 μg/g in the IORA group and 4.4 μg/g in the IV systemic group (P < .01). Mean tissue concentrations in bones were 34.4 μg/g in the IORA group and 6.1 μg/g in the IV systemic group (P < .01). Low-dose IORA was effective in the high-BMI population group, providing tissue concentrations of vancomycin 5-9 times higher than systemic administration. IORA optimizes timing of vancomycin administration and provides high tissue antibiotic concentrations during TKA in this high-risk patient group. Copyright © 2018 Elsevier Inc. All rights reserved.

[Osteogenesis imperfecta. Clinical, functional and multidisciplinary evaluation of 65 patients].

PubMed

Fano, V; Rodríguez Celin, M; Del Pino, M; Buceta, S; Obregón, M G; Primomo, C; García, H; Miscione, H; Lejarraga, H

2010-05-01

Osteogenesis Imperfecta (OI) is a genetic disease, in which the main clinical features are increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. Sixty-five children seen in a Paediatric Hospital during six months in 2007 were evaluated. Thirty-five were type I OI, and thirty were types III-IV. Median age was 7.8 years (range 1.9-19.2); mean length of follow up was 4.7 years. The majority of children attended regular school for their corresponding age. Mean height was -1.4 sDS and -5.64 sDS in types I and III-IV respectively. Nineteen percent of patients were overweight and 11% were obese. Mean age at first orthopaedic surgery inserting telescopic rods was 6.5 years. Scoliosis was present in 44.6% of patients and was directly related to severity. Bleck's motor scale showed that 93% of patients with mild forms and 29% of severe forms had a sustainable walking ability. A wheelchair was used by 25% of patients. Family inheritance was confirmed in 65% of cases. Integral care using a multidisciplinary approach is required due to the complexity and clinical variability of the condition. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Use of Antibiotic Impregnated Resorbable Beads Reduces Pressure Ulcer Recurrence: A Retrospective Analysis.

PubMed

Khansa, Ibrahim; Barker, Jenny C; Ghatak, Piya Das; Sen, Chandan K; Gordillo, Gayle M

2018-05-17

Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic- beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic-impregnated beads were compared to those who did not. 86 patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used, and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p=0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p=0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

Minimally invasive locked plating of distal tibia fractures is safe and effective.

PubMed

Ronga, Mario; Longo, Umile Giuseppe; Maffulli, Nicola

2010-04-01

Distal tibial fractures are difficult to manage. Limited soft tissue and poor vascularity impose limitations for traditional plating techniques that require large exposures. The nature of the limitations for traditional plating techniques is intrinsic to the large exposure required to approach distal tibia, a bone characterized by limited soft tissue coverage and poor vascularity. The locking plate (LP) is a new device for treatment of fractures. We assessed the bone union rate, deformity, leg-length discrepancy, ankle range of motion, return to preinjury activities, infection, and complication rate in 21 selected patients who underwent minimally invasive osteosynthesis of closed distal tibia fractures with an LP. According to the AO classification, there were 12 Type A, 5 Type B, and 4 Type C fractures. The minimum followup was 2 years (average, 2.8 years; range, 2-4 years). Two patients were lost to followup. Union was achieved in all but one patient by the 24th postoperative week. Four patients had angular deformity less than 7 degrees . No patient had a leg-length discrepancy more than 1.1 cm. Five patients had ankle range of motion less than 20 degrees compared with the contralateral side. Sixteen patients had not returned to their preinjury sporting or leisure activities. Three patients developed a delayed infection. We judge the LP a reasonable device for treating distal tibia fractures. The level of physical activities appears permanently reduced in most patients. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

PubMed Central

Terpos, Evangelos; Morgan, Gareth; Dimopoulos, Meletios A.; Drake, Matthew T.; Lentzsch, Suzanne; Raje, Noopur; Sezer, Orhan; García-Sanz, Ramón; Shimizu, Kazuyuki; Turesson, Ingemar; Reiman, Tony; Jurczyszyn, Artur; Merlini, Giampaolo; Spencer, Andrew; Leleu, Xavier; Cavo, Michele; Munshi, Nikhil; Rajkumar, S. Vincent; Durie, Brian G.M.; Roodman, G. David

2013-01-01

Purpose The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease. Methodology An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Recommendations Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability. PMID:23690408

Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

ClinicalTrials.gov

2018-04-02

Clear Cell Renal Cell Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Penile Carcinoma; Renal Pelvis Urothelial Carcinoma; Squamous Cell Carcinoma of the Penis; Stage III Bladder Adenocarcinoma AJCC v6 and v7; Stage III Bladder Squamous Cell Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Penile Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Renal Pelvis Cancer AJCC v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IIIa Penile Cancer AJCC v7; Stage IIIb Penile Cancer AJCC v7; Stage IV Bladder Adenocarcinoma AJCC v7; Stage IV Bladder Squamous Cell Carcinoma AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

[Regional blood flow and bone uptake of methylene-diphosphonate-technetium-99m].

PubMed

Vattimo, A; Martini, G; Pisani, M

1983-05-30

Sudeck's atrophy of the foot is an acute, patchy osteoporosis that, on bone scan, shows an increase in both bone blood flow and local bone uptake of bone-seeking radionuclides. The purpose of this study was to evaluate the relationship between bone uptake of 99mTc-MDP and local bone blood flow. In some patients with Sudeck's atrophy of one foot we measured local bone blood flow and bone uptake of 99mTc-MDP. External counting of radioactivity, with a count-rate of 1 second was performed for 60 minutes after i.v. injection of a known dose of 99mTc-MDP in some patients with Sudeck's atrophy of the foot. The regions of interest (ROI) were selected on the basis of a bone scan performed 24 hours earlier. We assumed that the data recorded during the first seconds (7-10) reflect local blood flow and the data at 60 minutes reflect the bone uptake. The ratio between the local blood flow in the involved and healthy foot was higher than the local bone uptake ratio. The ratio between bone uptake and local bone blood flow was higher in the normal foot than in the affected one. These results suggest that the bone avidity for bone-seeking radionuclides is lower in Sudeck's atrophy than in normal bone.

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

PubMed

Surrey, Eric; Taylor, Hugh S; Giudice, Linda; Lessey, Bruce A; Abrao, Mauricio S; Archer, David F; Diamond, Michael P; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Singh, Sukhbir S; Rechberger, Tomasz; Agarwal, Sanjay K; Duan, W Rachel; Schwefel, Brittany; Thomas, James W; Peloso, Paul M; Ng, Juki; Soliman, Ahmed M; Chwalisz, Kristof

2018-06-06

To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV=50.8%) and 78.1% at 200 mg twice daily (Elaris EM-IV=75.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.8% at 150 mg once daily (Elaris EM-IV=66.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV=67.2%). After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use. ClinicalTrials.gov, NCT01760954 and NCT02143713.

Extension of the classical classification of β-turns

PubMed Central

de Brevern, Alexandre G.

2016-01-01

The functional properties of a protein primarily depend on its three-dimensional (3D) structure. These properties have classically been assigned, visualized and analysed on the basis of protein secondary structures. The β-turn is the third most important secondary structure after helices and β-strands. β-turns have been classified according to the values of the dihedral angles φ and ψ of the central residue. Conventionally, eight different types of β-turns have been defined, whereas those that cannot be defined are classified as type IV β-turns. This classification remains the most widely used. Nonetheless, the miscellaneous type IV β-turns represent 1/3rd of β-turn residues. An unsupervised specific clustering approach was designed to search for recurrent new turns in the type IV category. The classical rules of β-turn type assignment were central to the approach. The four most frequently occurring clusters defined the new β-turn types. Unexpectedly, these types, designated IV1, IV2, IV3 and IV4, represent half of the type IV β-turns and occur more frequently than many of the previously established types. These types show convincing particularities, in terms of both structures and sequences that allow for the classical β-turn classification to be extended for the first time in 25 years. PMID:27627963

Extension of the classical classification of β-turns.

PubMed

de Brevern, Alexandre G

2016-09-15

The functional properties of a protein primarily depend on its three-dimensional (3D) structure. These properties have classically been assigned, visualized and analysed on the basis of protein secondary structures. The β-turn is the third most important secondary structure after helices and β-strands. β-turns have been classified according to the values of the dihedral angles φ and ψ of the central residue. Conventionally, eight different types of β-turns have been defined, whereas those that cannot be defined are classified as type IV β-turns. This classification remains the most widely used. Nonetheless, the miscellaneous type IV β-turns represent 1/3(rd) of β-turn residues. An unsupervised specific clustering approach was designed to search for recurrent new turns in the type IV category. The classical rules of β-turn type assignment were central to the approach. The four most frequently occurring clusters defined the new β-turn types. Unexpectedly, these types, designated IV1, IV2, IV3 and IV4, represent half of the type IV β-turns and occur more frequently than many of the previously established types. These types show convincing particularities, in terms of both structures and sequences that allow for the classical β-turn classification to be extended for the first time in 25 years.

Health outcomes of neonates with osteogenesis imperfecta: a cross-sectional study.

PubMed

Yimgang, Doris P; Brizola, Evelise; Shapiro, Jay R

2016-12-01

To assess at-birth health outcomes of neonates with osteogenesis imperfecta (OI). A total of 53 women who self-reported having had at least one child with OI completed the survey. We evaluated pregnancy length, neonatal intensive care unit (NICU) usage, at-birth complications, and the child's clinical information including OI type, height and weight. Information was gathered on a total of 77 children (60 type I, 4 type III and 13 type IV). Health conditions reported at birth included breech presentation (24%), prematurity (27%), fracture (18%), bone deformity (18%) and respiratory problems (22%). Approximately 31% (n = 24) received NICU care. There was a significant association between younger maternal age, preterm delivery and NICU admission. Our findings suggest that newborns with OI appear to be at high risk of skeletal disorders, preterm delivery and breech presentation. Younger maternal age and preterm delivery seem to be strong predictors of the need for NICU care. Our data suggest that pregnant women with OI younger than 20 years of age may benefit from added clinical supervision in anticipation of adverse effects on their child.

Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer.

PubMed

Yasumoto, Makiko; Sakamoto, Etsuko; Ogasawara, Sachiko; Isobe, Taro; Kizaki, Junya; Sumi, Akiko; Kusano, Hironori; Akiba, Jun; Torimura, Takuji; Akagi, Yoshito; Itadani, Hiraku; Kobayashi, Tsutomu; Hasako, Shinichi; Kumazaki, Masafumi; Mizuarai, Shinji; Oie, Shinji; Yano, Hirohisa

2017-01-01

The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein-coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin-like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria gonorrhoeae type IV secretion system.

PubMed

Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P

2007-08-01

Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.

Investigations into Changes in Bone Turnover with Acute, Weight-Bearing Exercise in Healthy, Young Men

DTIC Science & Technology

2009-10-01

four days post-exercise and is unaffected by training status. In physically - active men, who have consumed an appropriate diet, two bouts of... physically - active men, who have consumed an appropriate diet, two bouts of moderate exercise separated by either 23 h or 3 h has no effect on bone...relative intensity would decrease with increased physical fitness. Given the results of Study IV, where β-CTX concentrations were higher, albeit

Osteoporosis and anorexia nervosa: relative role of endocrine alterations and malnutrition.

PubMed

Jacoangeli, F; Zoli, A; Taranto, A; Staar Mezzasalma, F; Ficoneri, C; Pierangeli, S; Menzinger, G; Bollea, M R

2002-09-01

Anorexia nervosa (AN) is a psychiatric disorder characterised by self-induced starvation or a very reduced caloric intake, and frequently by severe life-threatening protein calory malnutrition. Its physiological consequences include amenorrhea, estrogen deficiency and osteoporosis. Osteoporosis may develop as a consequence of a lack of estrogens, low calcium or vitamin D intake, hypercortisolemia or the duration of the illness. The aim of this study was to identify the best endocrinological and nutritional indicators of bone density. The study involved 49 young females with AN and malnutrition and 24 age-matched normal controls in whom AN had been excluded on the basis of a clinical evaluation using DSM IV criteria. We studied bone density in early osteopenia, a condition in which the potential risk of fractures is certainly high and traditionally related to a variety of endocrinological and nutritional factors. Bone density was significantly lower in the AN than the control group in all of the examined bone districts: bone mineral density (BMD) spine 0.89 +/- 0.19 vs 1.27 +/- 0.2 (p<0.0001), BMD neck 0.75 +/- 0.14 vs 1.08 +/- 0.17 (p<0.001), BMD Ward 0.74 +/- 0.17 vs 1.12 +/- 0.11 (p<0.0001). Non-significant differences were found in the patients who had undergone previous estrogen medication. Body mass index (BMI) correlated with bone density, but caloric and calcium intake were not significant predictors. IGF-1, a known nutritionally dependent trophic bone factor, was significantly reduced in our patients but did not correlate with BMD. Like other authors, we found a close correlation between lean body mass and BMD in neck and spine. Physical exercise, urinary free cortisol osteocalcin and type I collagen-telopeptide (NTX) did not significantly correlate with the degree of osteopenia. Our data suggest the importance of nutritional factors (particularly lean body mass and BMI) in determining bone mass, and the relatively limited importance of endocrinological factors with the exception of the duration of amenorrhea as an indirect indicator of endocrinological status.

9 CFR 320.1 - Records required to be kept.

Code of Federal Regulations, 2010 CFR

2010-01-01

... processing procedures to destroy trichinae in § 318.10(c)(3)(iv) (Methods 5 and 6). (8) Records of nutrition... control of the production process using advanced meat/bone separation machinery and meat recovery systems...

Fosfomycin i.v. for Treatment of Severely Infected Patients

ClinicalTrials.gov

2018-05-08

Bacterial Infections; Bone Diseases, Infectious; Osteomyelitis; Central Nervous System Bacterial Infections; Meningitis, Bacterial; Encephalitis; Brain Abscess; Urinary Tract Infections; Respiratory Tract Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Intraabdominal Infections; Sepsis; Bacteremia; Endocarditis, Bacterial

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

PubMed

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome.

PubMed

Ganaha, Akira; Kaname, Tadashi; Yanagi, Kumiko; Naritomi, Kenji; Tono, Tetsuya; Usami, Shin-ichi; Suzuki, Mikio

2013-05-24

Pendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okinawa Island and those from the main islands of Japan. To confirm the ethnic variation of the spectrum of SLC26A4 mutations, we investigated the frequencies of SLC26A4 mutations and clinical manifestations of patients with EVA or PS living in the Okinawa Islands. We examined 22 patients with EVA or PS from 21 unrelated families in Okinawa Islands. The patient's clinical history, findings of physical and otoscopic examinations, hearing test, and computed tomography (CT) scan of the temporal bones were recorded. To detect mutations, all 21 exons and the exon-intron junctions of SLC26A4 were sequenced for all subjects. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for SLC26A4 and calculations using the comparative CT (2(-ΔΔCT)) method were used to determine the pathogenicity associated with gene substitutions. SLC26A4 mutations were identified in 21 of the 22 patients. We found a compound heterozygous mutation for IVS15 + 5G > A/H723R in nine patients (41%), a homozygous substitution of IVS15 + 5G > A in six patients (27%), and homozygous mutation for H723R in five patients (23%). The most prevalent types of SLC26A4 alleles were IVS15 + 5G > A and H723R, which both accounted for 15/22 (68%) of the patients. There were no significant correlations between the types of SLC26A4 mutation and clinical manifestations. Based on qRT-PCR results, expression of SLC26A4 was not identified in patients with the homozygous substitution of IVS15 + 5G > A. The substitution of IVS15 + 5G > A in SLC26A4 was the most common mutation in uniquely found in patients with PS and EVA in Okinawa Islands. This suggested that the spectrum of SLC26A4 mutation differed from main islands of Japan and other East Asian countries. The substitution of IVS15 + 5G > A leads to a loss of SLC26A expression and results in a phenotype of PS and EVA.

Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome

PubMed Central

2013-01-01

Background Pendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okinawa Island and those from the main islands of Japan. To confirm the ethnic variation of the spectrum of SLC26A4 mutations, we investigated the frequencies of SLC26A4 mutations and clinical manifestations of patients with EVA or PS living in the Okinawa Islands. Methods We examined 22 patients with EVA or PS from 21 unrelated families in Okinawa Islands. The patient’s clinical history, findings of physical and otoscopic examinations, hearing test, and computed tomography (CT) scan of the temporal bones were recorded. To detect mutations, all 21 exons and the exon–intron junctions of SLC26A4 were sequenced for all subjects. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for SLC26A4 and calculations using the comparative CT (2−ΔΔCT) method were used to determine the pathogenicity associated with gene substitutions. Results SLC26A4 mutations were identified in 21 of the 22 patients. We found a compound heterozygous mutation for IVS15 + 5G > A/H723R in nine patients (41%), a homozygous substitution of IVS15 + 5G > A in six patients (27%), and homozygous mutation for H723R in five patients (23%). The most prevalent types of SLC26A4 alleles were IVS15 + 5G > A and H723R, which both accounted for 15/22 (68%) of the patients. There were no significant correlations between the types of SLC26A4 mutation and clinical manifestations. Based on qRT-PCR results, expression of SLC26A4 was not identified in patients with the homozygous substitution of IVS15 + 5G > A. Conclusions The substitution of IVS15 + 5G > A in SLC26A4 was the most common mutation in uniquely found in patients with PS and EVA in Okinawa Islands. This suggested that the spectrum of SLC26A4 mutation differed from main islands of Japan and other East Asian countries. The substitution of IVS15 + 5G > A leads to a loss of SLC26A expression and results in a phenotype of PS and EVA. PMID:23705809

Uremic toxin and bone metabolism.

PubMed

Iwasaki, Yoshiko; Yamato, Hideyuki; Nii-Kono, Tomoko; Fujieda, Ayako; Uchida, Motoyuki; Hosokawa, Atsuko; Motojima, Masaru; Fukagawa, Masafumi

2006-01-01

Patients with end-stage renal disease (ESRD) develop various kinds of abnormalities in bone and mineral metabolism, widely known as renal osteodystrophy (ROD). Although the pathogenesis of ESRD may be similar in many patients, the response of the bone varies widely, ranging from high to low turnover. ROD is classified into several types, depending on the status of bone turnover, by histomorphometric analysis using bone biopsy samples [1,2]. In the mild type, bone metabolism is closest to that of persons with normal renal function. In osteitis fibrosa, bone turnover is abnormally activated. This is a condition of high-turnover bone. A portion of the calcified bone loses its lamellar structure and appears as woven bone. In the cortical bone also, bone resorption by osteoclasts is active, and a general picture of bone marrow tissue infiltration and the formation of cancellous bone can be observed. In osteomalacia, the bone surface is covered with uncalcified osteoid. This condition is induced by aluminum accumulation or vitamin D deficiency. The mixed type possesses characteristics of both osteitis fibrosa and osteomalacia. The bone turnover is so markedly accelerated that calcification of the osteoid cannot keep pace. In the adynamic bone type, bone resorption and bone formation are both lowered. While bone turnover is decreased, there is little osteoid. The existence of these various types probably accounts for the diversity in degree of renal impairment, serum parathyroid hormone (PTH) level, and serum vitamin D level in patients with ROD. However, all patients share a common factor, i.e., the presence of a uremic condition.

Bone Cancer—Health Professional Version

Cancer.gov

There are several types of bone cancer. Osteosarcoma usually starts in osteoblasts, a type of bone cell that becomes new bone tissue. Ewing sarcoma arises from a primordial bone marrow–derived mesenchymal stem cell. Find evidence-based information on bone cancer including treatment, research, genetics, and statistics.

Effect of cisplatin on bone transport osteogenesis in dogs.

PubMed

Ehrhart, Nicole; Eurell, Jo Ann C; Tommasini, Matteo; Constable, Peter D; Johnson, Ann L; Feretti, Antonio

2002-05-01

To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis. 10 skeletally mature hounds. Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups. Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups. Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA.

Nurse exposure doses resulted from bone scintigraphy patient

NASA Astrophysics Data System (ADS)

Tunçman, Duygu; Kovan, Bilal; Poyraz, Leyla; ćapali, Veli; Demir, Bayram; Türkmen, Cüneyt

2016-03-01

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It's general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget's disease, investigation of loosening and infection in orthopedic implants. It is applied with using 99mTc labeled radiopharmaceuticals (e.g 99m Tc MDP,99mTc HEDP and 99mTc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. When some patient's situation is not good, patients are hospitalized until the scanning because of patients' close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse's exposure radiations from patient's routine treatment, examination and emergency station.

Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta

PubMed Central

Meganck, J.A.; Begun, D.L.; McElderry, J.D.; Swick, A.; Kozloff, K.M.; Goldstein, S.A.; Morris, M.D.; Marini, J.C.; Caird, M.S.

2014-01-01

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5 weeks of healing, tibiae were assessed using microcomputed tomography (μCT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5 weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl/+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture. PMID:23774443

Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization.

PubMed

Cui, X; Chen, J; Zacharek, A; Roberts, C; Savant-Bhonsale, S; Chopp, M

2008-09-22

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate) and bone marrow stromal cells promotes functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates angiopoietin-1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhancing cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were i.v. administered PBS, bone marrow stromal cells 5x10(5), DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean+ or -S.E., P<0.05). In vitro, DETA-NONOate significantly increased angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (P<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cell-conditioned medium compared with cells treated with bone marrow stromal cell-conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared with vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the angiopoietin-1/Tie2 axis.

Indian girls have higher bone mineral content per unit of lean body than boys through puberty.

PubMed

Khadilkar, Anuradha V; Sanwalka, Neha; Mughal, M Zulf; Chiplonkar, Shashi; Khadilkar, Vaman

2018-05-01

Our aim is to describe changes in the muscle-bone unit assessed as a ratio of bone mineral content (BMC) to lean body mass (LBM) through puberty at total body and various skeletal sites in Indian boys and girls. A cross-sectional study was conducted (888 children, 480 boys, aged 5-17 years) in Pune, India. Pubertal staging was assessed. BMC, LBM and fat percentage at the arms, legs, android, gynoid and total body (less the head) were assessed by dual energy X-ray absorptiometry. The amount of BMC per unit LBM (BMC/LBM) was computed. Changes in mean BMC/LBM at 5 Tanner (pubertal) stages after adjustment for age and fat percentage were calculated. In boys, adjusted BMC/LBM was significantly higher with successive Tanner stages [legs (TS-II vs TS-I), android (TS-III vs TS-II, TS-IV vs TS-III) and gynoid region (TS-III vs TS-II and TS-II vs TS-I) (p < 0.05)]. In girls, adjusted BMC/LBM was significantly higher with successive Tanner stages at total body, legs and gynoid (TS-III vs TS-II; TS-II vs TS-I; TS-V vs TS-IV), arms (TS-I to TS-V) and android regions (TS-V vs TS-IV) (p < 0.05). Boys had significantly higher adjusted BMC/LBM than girls at earlier Tanner stages (TS-I to TS-III), whereas girls had significantly higher adjusted BMC/LBM than boys at later Tanner stages (TS-IV, TS-V) (p < 0.05). Indian boys and girls showed higher total and regional body, and age- and fat percentage-adjusted BMC/LBM with successive pubertal stages. Girls had higher BMC/LBM than boys which may possibly act as a reservoir for later demands of pregnancy and lactation.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on hearing level.

PubMed

Doherty, Joni K; Linthicum, Fred H

2004-07-01

To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression. Retrospective. Tertiary referral center. Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization. Audiography. Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques. Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent. These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.

Stem cells from human fat as cellular delivery vehicles in an athymic rat posterolateral spine fusion model.

PubMed

Hsu, Wellington K; Wang, Jeffrey C; Liu, Nancy Q; Krenek, Lucie; Zuk, Patricia A; Hedrick, Marc H; Benhaim, Prosper; Lieberman, Jay R

2008-05-01

Mesenchymal stem cells derived from human liposuction aspirates, termed processed lipoaspirate cells, have been utilized as cellular delivery vehicles for the induction of bone formation in tissue engineering and gene therapy strategies. In this study, we sought to evaluate the efficacy of bone morphogenetic protein (BMP)-2-producing adipose-derived stem cells in inducing a posterolateral spine fusion in an athymic rat model. Single-level (L4-L5) intertransverse spinal arthrodesis was attempted with use of a type-I collagen matrix in five groups of athymic rats, with eight animals in each group. Group I was treated with 5 x 10(6) adipose-derived stem cells transduced with an adenoviral vector containing the BMP-2 gene; group II, with 5 x 10(6) adipose-derived stem cells treated with osteogenic media and 1 microg/mL of recombinant BMP-2 (rhBMP-2); group III, with 10 microg of rhBMP-2; group IV, with 1 microg of rhBMP-2; and group V, with 5 x 10(6) adipose-derived stem cells alone. The animals that showed radiographic evidence of healing were killed four weeks after cell implantation and were examined with plain radiographs, manual palpation, microcomputed tomography scanning, and histological analysis. All eight animals in group I demonstrated successful spinal fusion, with a large fusion mass, four weeks postoperatively. Furthermore, group-I specimens consistently revealed spinal fusion at the cephalad level (L3 and L4), where no fusion bed had been prepared surgically. In contrast, despite substantial BMP-2 production measured in vitro, group-II animals demonstrated minimal bone formation even eight weeks after implantation. Of the groups treated with the application of rhBMP-2 alone, the one that received a relatively high dose (group III) had a higher rate of fusion (seen in all eight specimens) than the one that received the low dose (group IV, in which fusion was seen in four of the eight specimens). None of the group-V animals (treated with adipose-derived stem cells alone) demonstrated successful spine fusion eight weeks after the surgery. Adipose-derived stem cells show promise as gene transduction targets for inducing bone formation to enhance spinal fusion in biologically stringent environments.

Genetics Home Reference: familial porencephaly

MedlinePlus

... one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex ... and support cells in many tissues. Type IV collagen networks play an important role in the basement ...

A type IV burst associated with a coronal streamer disruption event

NASA Technical Reports Server (NTRS)

Kundu, M. R.

1987-01-01

A type IV burst was observed on February 17, 1985 with the Clark Lake Radio Observatory multifrequency radioheliograph operating in the frequency range 20-125 MHz. This burst was associated with a coronal streamer disruption event. From two-dimensional images produced at 50 MHz, evidence of a type II burst and a slow moving type IV burst are shown. The observations of the moving type IV burst suggests that a plasmoid containing energetic electrons can result from the disruption of a coronal streamer.

Stress distribution in fixed-partial prosthesis and peri-implant bone tissue with different framework materials and vertical misfit levels: a three-dimensional finite element analysis.

PubMed

Bacchi, Ataís; Consani, Rafael L X; Mesquita, Marcelo F; dos Santos, Mateus B F

2013-09-01

The purpose of this study was to evaluate the influence of superstructure material and vertical misfits on the stresses created in an implant-supported partial prosthesis. A three-dimensional (3-D) finite element model was prepared based on common clinical data. The posterior part of a severely resorbed jaw with two osseointegrated implants at the second premolar and second molar regions was modeled using specific modeling software (SolidWorks 2010). Finite element models were created by importing the solid model into mechanical simulation software (ANSYS Workbench 11). The models were divided into groups according to the prosthesis framework material (type IV gold alloy, silver-palladium alloy, commercially pure titanium, cobalt-chromium alloy, or zirconia) and vertical misfit level (10 µm, 50 µm, and 100 µm) created at one implant-prosthesis interface. The gap of the vertical misfit was set to be closed and the stress values were measured in the framework, porcelain veneer, retention screw, and bone tissue. Stiffer materials led to higher stress concentration in the framework and increased stress values in the retention screw, while in the same circumstances, the porcelain veneer showed lower stress values, and there was no significant difference in stress in the peri-implant bone tissue. A considerable increase in stress concentration was observed in all the structures evaluated within the misfit amplification. The framework material influenced the stress concentration in the prosthetic structures and retention screw, but not that in bone tissue. All the structures were significantly influenced by the increase in the misfit levels.

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism

PubMed Central

Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

2017-01-01

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor–host cell dynamics, tumor tropism, and hematopoietic cell transplantation. PMID:28484009

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

PubMed

Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

2017-05-23

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor-host cell dynamics, tumor tropism, and hematopoietic cell transplantation.

Calcium phosphate cement augmentation in the treatment of depressed tibial plateau fractures with open reduction and internal fixation.

PubMed

Oztürkmen, Yusuf; Caniklioğlu, Mustafa; Karamehmetoğlu, Mahmut; Sükür, Erhan

2010-01-01

We aimed to evaluate the clinical and radiological outcomes of open reduction and internal fixation augmented with calcium phosphate cement (CPC) in the treatment of depressed tibial plateau fractures. Twenty-eight knees of 28 patients [19 males and 9 females; mean age, 41.2 years (range 22-72 years)] who had open reduction and internal fixation combined with CPC augmentation were included in this study. Seventeen fractures were Schatzker type II, 5 were type III, 3 were type IV, 2 were type V, and 1 was type VI. CPC was used to fill the subchondral bone defects in all knees. Fixation of the fragments was done with screws in 3 knees (10%). Standard proximal tibial plates or buttress plates were used in 25 knees (90%) with an additional split fragment extending distally to achieve internal fixation. Full weight-bearing was allowed in 6.4 weeks (range 6-12 weeks) after surgery. Resorption of CPC granules was defined as the decrease in the size and density of grafting material on radiographs. Rasmussen's radiological and clinical scores were determined postoperatively. Functionality was assessed with Lysholm knee scoring system. Activity was graded with Tegner's activity scale. Union was achieved in all patients with a mean follow-up of 22.2 months (range 6-36 months). There were no intraoperative complications. At the latest follow-up radiographs, resorption of the graft was observed in 25 knees (89%). Rasmussen's radiologic score was excellent in 17 patients (61%), good in 9 patients (32%), and fair in 2 patients (7%). Rasmussen's clinical score was excellent in 9 patients (32%), good in 18 patients (64%), and fair in 1 patient (4%). According to the Lysholm knee score, functional results were excellent in 16 patients (57%), good in 8 patients (29%), and fair in 4 patients (14%). Twenty-two patients (78%) achieved the preoperative activity level after surgery, and there was no significant difference between the mean preoperative and postoperative Tegner scores (4.11±0.68 and 4.04±0.64, respectively, p=0.161). CPC is a safe biomaterial with many advantages in augmenting the open reduction and internal fixation of depressed tibial plateau fractures, including elimination of morbidity associated with bone graft harvesting, the unlimited supply of bone substitute, the optimum filling of irregular bone defects, and shortening of the postoperative full weight-bearing time.

Archaeological Investigation in the Gainesville Lake Area of the Tennessee-Tombigbee Waterway. Volume IV. Biocultural Studies in the Gainesville Lake Area.

DTIC Science & Technology

1981-01-01

response. Because bone is limited in its ability to respond to external and internal stimuli, unlike soft tissues which show change in color, etc., a...al. 1978). Because bone is limited in its ability to respond to external and internal stimuli (unlike soft tissues which show change in color, etc...aie gingival tissues . There is also evidence of alveolar abscessing, periodontal diseast, 305 numerous caries, extreme attrition and heavy dental

Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer

ClinicalTrials.gov

2018-05-29

Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

ClinicalTrials.gov

2018-05-25

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Cancer AJCC v7

Genetics Home Reference: multicentric osteolysis, nodulosis, and arthropathy

MedlinePlus

... to cut (cleave) a protein called type IV collagen. Type IV collagen is a major structural component of basement membranes, ... enzyme, preventing the normal cleavage of type IV collagen. It is unclear how a loss of enzyme ...

viking: identification and characterization of a second type IV collagen in Drosophila.

PubMed

Yasothornsrikul, S; Davis, W J; Cramer, G; Kimbrell, D A; Dearolf, C R

1997-10-01

We have taken an enhancer trap approach to identify genes that are expressed in hematopoietic cells and tissues of Drosophila. We conducted a molecular analysis of two P-element insertion strains that have reporter gene expression in embryonic hemocytes, strain 197 and vikingICO. This analysis has determined that viking encodes a collagen type IV gene, alpha2(IV). The viking locus is located adjacent to the previously described DCg1, which encodes collagen alpha1(IV), and in the opposite orientation. The alpha2(IV) and alpha1(IV) collagens are structurally very similar to one another, and to vertebrate type IV collagens. In early development, viking and DCg1 are transcribed in the same tissue-specific pattern, primarily in the hemocytes and fat body cells. Our results suggest that both the alpha1 and alpha2 collagen IV chains may contribute to basement membranes in Drosophila. This work also provides the foundation for a more complete genetic dissection of collagen type IV molecules and their developmental function in Drosophila.

Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance

DTIC Science & Technology

2008-05-01

osteoblast proliferation but does not induce bone matrix protein (bone sialoprotein , type I collagen, osteocalcin, and osteopontin) mRNA expression...are incompletely understood. AM treatment stimulates osteoblast proliferation but does not induce bone matrix protein (bone sialoprotein , type I

Towards Standardized Stem Cell Therapy in Type 2 Diabetes Mellitus: A Systematic Review.

PubMed

Pawitan, Jeanne Adiwinata; Yang, Zheng; Wu, Ying Nan; Leed, Eng Hin

2018-05-02

To compile and analyze the published studies on cell therapy for type 2 diabetes mellitus (T2DM) to obtain a better insight into management of T2DM that involved stem cell therapy. We searched all published studies in Pubmed/Medline, and Cochrane library, using keywords: 'stem cell' AND 'therapy' AND 'diabetes type 2'. original articles on the use of stem cells in humans with T2DM. articles in the non-English literature, studies on T2DM complications that did not assess both adverse events and any of the common diabetes study outcomes. type of study, number of cases, and all data that were related to outcome and adverse events. Data were analyzed descriptively to conclude the possible cause of adverse reactions, and which protocols gave a satisfactory outcome. We collected 26 original articles, out of which 17 studies did not have controls and were classified as case reports, while there were 8 studies that were controlled clinical trials. Most studies used autologous bone marrow mononuclear cells (BM-MNCs) or autologous or allogeneic mesenchymal stem cells (MSCs) from various sources. Adverse events were mild and mostly intervention related. Efficacy of autologous BM-MNCs that were given via interventional route was comparable to Wharton jelly or umbilical cord MSCs that were given via intravenous (IV), Intra muscular (IM), or subcutaneous (SC) route. Further controlled studies that compare BM-MNCs to BM-MSCs or WJ-MSCs or UCSCs are recommended to prove their comparable efficacy. In addition, studies that compare various routes of administration (IV, IM or SC) versus the more invasive interventional routes are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Distribution of type IV collagen in pancreatic adenocarcinoma and chronic pancreatitis.

PubMed Central

Lee, C. S.; Montebello, J.; Georgiou, T.; Rode, J.

1994-01-01

Changes in the basement membrane are present in various neoplastic conditions such as neurofibrosarcoma, cervical carcinoma, colorectal cancers and hepatoblastoma. This study examines the expression of type IV collagen in the basement membrane, using an immunohistochemical method, in the normal pancreas (n = 10), chronic pancreatitis (n = 15) and pancreatic adenocarcinoma (n = 30). The formalin fixed, paraffin embedded tissue was sectioned and pretreated with protease prior to immunostaining for type IV collagen. There was a statistically significant difference in type IV collagen expression between pancreatic carcinoma and chronic pancreatitis (P = 0.0001; chi 2 test with continuity correction). In pancreatic adenocarcinoma, type IV collagen distribution in the basement membrane was discontinuous and irregular or absent around individual or groups of neoplastic cells (n = 30). Most cases of chronic pancreatitis showed continuous pattern of basement membrane type IV collagen around residual ducts (n = 10). In the normal pancreas, only one of the ten cases showed discontinuous basement membrane around pancreatic ducts, while in the rest of the cases, the pattern was continuous. This study suggests that there is abnormal distribution of type IV collagen in the basement membrane in pancreatic carcinoma, which may be related to either abnormal deposition or degradation of the collagen. Immunostaining for type IV collagen may be of some diagnostic use for distinguishing pancreatic adenocarcinoma from problematic cases of chronic pancreatitis. Images Figure 1 Figure 2 Figure 3 PMID:8199008

Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

PubMed

Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2016-09-01

Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetics Home Reference: hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome

MedlinePlus

... one component of a protein called type IV collagen . Type IV collagen molecules attach to each other to form complex ... and support cells in many tissues. Type IV collagen networks play an important role in the basement ...

Type IV collagen is a novel DEJ biomarker that is reduced by radiotherapy.

PubMed

McGuire, J D; Gorski, J P; Dusevich, V; Wang, Y; Walker, M P

2014-10-01

The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy--teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy. © International & American Associations for Dental Research.

Type IV Collagen is a Novel DEJ Biomarker that is Reduced by Radiotherapy

PubMed Central

McGuire, J.D.; Gorski, J.P.; Dusevich, V.; Wang, Y.; Walker, M.P.

2014-01-01

The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy – teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy. PMID:25146181

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

PubMed Central

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. PMID:26069692

Paracrine Effects of Bone Marrow Soup Restore Organ Function, Regeneration, and Repair in Salivary Glands Damaged by Irradiation

PubMed Central

Tran, Simon D.; Liu, Younan; Xia, Dengsheng; Maria, Ola M.; Khalili, Saeed; Wang, Renee Wan-Jou; Quan, Vu-Hung; Hu, Shen; Seuntjens, Jan

2013-01-01

Background There are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. Methods To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as “BM Soup”) injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup’s donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. Results BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. Conclusion BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs. PMID:23637870

Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation.

PubMed

Tran, Simon D; Liu, Younan; Xia, Dengsheng; Maria, Ola M; Khalili, Saeed; Wang, Renee Wan-Jou; Quan, Vu-Hung; Hu, Shen; Seuntjens, Jan

2013-01-01

There are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as "BM Soup") injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup's donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs.

Behavior of scoliosis during growth in children with osteogenesis imperfecta.

PubMed

Anissipour, Alireza K; Hammerberg, Kim W; Caudill, Angela; Kostiuk, Theodore; Tarima, Sergey; Zhao, Heather Shi; Krzak, Joseph J; Smith, Peter A

2014-02-05

Spinal deformities are common in patients with osteogenesis imperfecta, a heritable disorder that causes bone fragility. The purpose of this study was to describe the behavior of spinal curvature during growth in patients with osteogenesis imperfecta and establish its relationship to disease severity and medical treatment with bisphosphonates. The medical records and radiographs of 316 patients with osteogenesis imperfecta were retrospectively reviewed. The severity of osteogenesis imperfecta was classified with the modified Sillence classification. Serial curve measurements were recorded throughout the follow-up period for each patient with scoliosis. Regression analysis was used to determine the effect of disease severity (Sillence type), patient age, and bisphosphonate treatment on the progression of scoliosis as measured with the Cobb method. Of the 316 patients with osteogenesis imperfecta, 157 had associated scoliosis, a prevalence of 50%. Scoliosis prevalence (68%) and mean progression rate (6° per year) were the highest in the group of patients with the most severe osteogenesis imperfecta (modified Sillence type III). A group with intermediate osteogenesis imperfecta severity, modified Sillence type IV, demonstrated intermediate scoliosis values (54%, 4° per year). The patient group with the mildest form of osteogenesis imperfecta, modified Sillence type I, had the lowest scoliosis prevalence (39%) and rate of progression (1° per year). Early treatment-before the patient reached the age of six years-of type-III osteogenesis imperfecta with bisphosphonate therapy decreased the curve progression rate by 3.8° per year, which was a significant decrease. Bisphosphonate treatment had no demonstrated beneficial effect on curve behavior in patients with other types of osteogenesis imperfecta or in patients of older age. The prevalence of scoliosis in association with osteogenesis imperfecta is high. Progression rates of scoliosis in children with osteogenesis imperfecta are variable, depending on the Sillence type of osteogenesis imperfecta. High rates of scoliosis progression in type-III and type-IV osteogenesis imperfecta contrast with a benign course in type I. Bisphosphonate therapy initiated before the patient reaches the age of six years can modulate curve progression in type-III osteogenesis imperfecta.

Addition of a Medial Locking Plate to an In Situ Lateral Locking Plate Results in Healing of Distal Femoral Nonunions.

PubMed

Holzman, Michael A; Hanus, Bryan D; Munz, John W; O'Connor, Daniel P; Brinker, Mark R

2016-06-01

Nonunion of the distal femur after lateral plating is associated with axial malalignment, chronic pain, loss of ambulatory function, and decreased knee ROM. The addition of a medial locking plate with autogenous bone grafting can provide greater stability to allow bone healing and may be used to achieve union in these challenging cases. We wished to determine (1) the proportion of patients who achieve radiographic signs of osseous union for distal femoral nonunions with an in situ lateral plate after treatment with addition of a medial locking plate and autogenous bone grafting, and (2) the frequency and types of complications associated with this treatment. Between 2007 and 2013, we treated 22 patients for 23 distal femoral nonunions, defined as an unhealed fracture with no radiographic signs of osseous union at a mean of 16 months (SD, 13 months) after injury. During that time, we used a treatment algorithm consisting of treatment in one or two stages. The single-stage procedure performed in 16 aseptic nonunions with a stable lateral plate involved addition of a medial locking plate and autogenous bone graft. A two-stage treatment performed in seven nonunions with lateral plate failure involved placement of a new lateral locking plate followed by addition of a medial locking plate with autogenous bone graft at least 2 months after the first procedure. Of the 22 patients treated, 20 had a median followup of 18 months (SD, 6-94 months). We defined osseous union by bridging bone on three of four cortices with absence of a radiolucent line or more than 25% cross-sectional area of bridging bone via CT. Twenty of the 21 nonunions attained radiographic signs of osseous union by 12 months. Six of the 20 patients experienced complications: one patient had a persistent nonunion; four patients underwent removal of symptomatic hardware; and one patient experienced skin breakdown at the bone graft harvest site. A very high proportion of patients achieve union when using medial locking plates to treat distal femoral nonunions after lateral plating of the original injury. Addition of bone graft, staged reconstruction, and revision of the initial lateral plate is indicated when the nonunion is associated with fatigue failure of the initial lateral plate. Level IV, therapeutic study.

Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide after Static and Dynamic Exercises

ERIC Educational Resources Information Center

Kubo, Keitaro; Yuki, Kazuhito; Ikebukuro, Toshihiro

2012-01-01

We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and pro-collagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic…

Correlation Between Resonance Frequency Analysis and Bone Quality Assessments at Dental Implant Recipient Sites.

PubMed

Fu, Min-Wen; Fu, Earl; Lin, Fu-Gong; Chang, Wei-Jeng; Hsieh, Yao-Dung; Shen, E-Chin

To evaluate whether primary implant stability could be used to predict bone quality, the association between the implant stability quotient (ISQ) value and the bone type at the implant site was evaluated. Ninety-five implant sites in 50 patients were included. Bone type (categorized by Lekholm and Zarb) at the implant site was initially assessed using presurgical dental radiography. During the preparation of the implant site, a bone core specimen was carefully obtained. The bone type was assessed by tactile sensation during the drilling operation, according to the Misch criteria. The primary stability of the inserted implant was evaluated by resonance frequency analysis (RFA). The ISQ value was recorded. The bone core specimen was then examined by stereomicroscopy or microcomputed tomography (micro-CT), and the bone type was determined by the surface characteristics of the specimen, based on Lekholm and Zarb classification. Agreement between the bone quality assessed by the four methods (ie, presurgical radiography, tactile sensation, stereomicroscopy, and micro-CT) was tested by Cohen's kappa statistics, whereas the association between the ISQ value and the bone type was evaluated by the generalized linear regression model. The mean ISQ score was 72.6, and the score was significantly influenced by the maxillary or mandibular arch (P = .001). The bone type at the implant sites varied according to the assessment method. However, a significant influence of the arch was repeatedly noted when using radiography or tactile sensation. Among the four bone-quality assessment methods, a weak agreement existed only between stereomicroscopy and micro-CT, especially in the maxilla (κ = 0.469). A negative association between the ISQ value and the bone type assessed by stereomicroscopy or by micro-CT was significant in the maxilla, but not in the mandible, after adjustments for sex, age, and right/left side (P = .013 and P = .027 for stereomicroscopy and micro-CT, respectively). The ISQ value was weakly associated with the bone type when assessed by stereomicroscopy or micro-CT in the maxilla. Caution is necessary if RFA is used as a tool to evaluate bone quality at the implant site, especially in the mandible.

Experiment M-6: Bone Demineralization

NASA Technical Reports Server (NTRS)

Mack, Pauline B.; Vose, George; Vogt, Fred B.; LaChance, Paul A.

1966-01-01

Densitometric evaluations of serial radiographs of "normal" subjects have often shown rather frequent changes in bone mass within relatively short periods of time. For this reason it was decided to make two pre-flight and two post flight radiographs of the Gemini V backup crew. In comparing the changes observed preflight and post flight as the conventional os calcis scanning site between the two crews, it was found that no changes greater than 4 percent were evident in either member of the backup crew. In comparing the changes observed preflight and postflight as the conventional o calcis scanning site between the two crews, it was found that no changes greater than 4 percent were evident in either member of the backup crew. This is in contract to the 15.1 and 8.9 percent losses observed in the prime crew. It has long been known that the skeletal system experiences a general loss of mineral under immobilization or extended bed rest. However, in both Gemini IV and Gemini V studies, bone mass losses were greater in both the os calcis and phalanx than were shown by the TWU bed-rest subjects during the same period of time. Although the bone mass losses in the 8-day Gemini V flight were generally greater than in the 4-day Gemini IV flight, the information to date is still insufficient to conclude that the losses tend to progress linearly with time, or whether a form of physiological adaptation may occur in longer space flights.

The effect of antilymphocytic antibody on the humoral immune response in different strains of mice

PubMed Central

Ghaffar, A.; James, K.

1973-01-01

The effect of a single batch of horse anti-mouse thymocyte globulin on the immune response to type III polysaccharide antigen has been investigated in 2–3-month-old male A/HeJ, C57B1, BALB/c, DBA/1, CBA and C3H mice. In almost all cases the intraperitoneal administration of 5 mg of this material on days –4 and –2 significantly suppressed the immune response to 0.1, 1.0 and 5.0 μg of antigen injected i.v. on day 0. Further studies undertaken in BALB/c mice indicated that effective suppression of the immune response to type III polysaccharide antigen could also be achieved by injecting 5 mg of this product (i.p.) some 15–30 minutes prior to antigenic challenge. Preliminary cell reconstitution studies in antilymphocytic antibody-treated CBA mice indicate that the ability to respond to type III polysaccharide can be partially restored by the injection of syngeneic thymocytes, bone marrow cells or spleen cells. PMID:4146227

Autologous bone marrow derived stem cell therapy in patients with type 2 diabetes mellitus - defining adequate administration methods

PubMed Central

Sood, Vikas; Bhansali, Anil; Mittal, Bhagwant Rai; Singh, Baljinder; Marwaha, Neelam; Jain, Ashish; Khandelwal, Niranjan

2017-01-01

AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy (ABMSCT) through different routes. METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separated and purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery (Group I), splenic artery (Group II) and through the peripheral intravenous route (Group III). Another group of 7 patients acted as controls and a sham procedure was carried out on them (Group IV). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability (P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters: (1) C-peptide assay; (2) HOMA-IR and HOMA-B; (3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and (4) reduction in HbA1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows: (1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant (P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups I to IV); (2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences (P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups I to IV); (3) Group Ishowed a significant reduction in Insulin dose requirement (P < 0.01). Group II patients also achieved a significant reduction in Insulin dosages (P = 0.01). The Group I and Group II patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group III, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement (P = 0.137). Group IV patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months (P < 0.05); and (4) there was a non-significant change in the Hb A1c levels at the end of 6 mo across all groups (P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups I to IV). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction. PMID:28751962

[Effect of different bone cement dispersion types in the treatment of osteoporotic vertebral compression fracture].

PubMed

Zhao, Yong-Sheng; Li, Qiang; Li, Qiang; Zheng, Yan-Ping

2017-05-25

To observe different bone cement dispersion types of PVP, PKP and manipulative reduction PVP and their effects in the treatment of senile osteoporotic vertebral compression fractures and the bone cement leakage rate. The clinical data of patients with osteoporotic vertebral compression fractures who underwent unilateral vertebroplasty from January 2012 to January 2015 was retrospectively analyzed. Of them, 56 cases including 22 males and 34 females aged from 60 to 78 years old were treated by PVP operation; Fouty-eight cases including 17 males and 31 females aged from 61 to 79 years old were treated by PKP operation; Forty-three cases including 15 males and 28 females aged from 60 to 76 years old were treated by manipulative reduction PVP operation. AP and lateral DR films were taken after the operation; the vertebral bone cement diffusion district area and mass district area were calculated with AutoCAD graphics processing software by AP and lateral DR picture, then ratio(K) of average diffusion area and mass area were calculated, defining K<50% as mass type, 50%<=K<=100% as mixed type and K>100% as diffusion type. Different bone cement dispersion types of PVP, PKP and manipulative reduction PVP operation were analyzed. According to bone cement dispersion types, patients were divided into diffusion type, mixed type and mass type groups.Visual analogue scale (VAS), vertebral body compression rate, JOA score and bone cement leakage rate were observed. All patients were followed up for 12-24 months with an average of 17.2 months. There was significant difference in bone cement dispersion type among three groups ( P <0.05). The constituent ratio of diffusion type, mixed type and mass type in PVP operation was 46.43%, 35.71%, 17.86%, in PKP was 16.67%, 37.50% , 45.83%, and in manipulative reduction PVP was 37.21%, 44.19% and 18.60%, respectively. PVP operation and manipulative reduction PVP were mainly composed of diffusion type and mixed type, while PKP was mainly composed of mass type and mixed type. There was no significant difference in VAS score, JOA score and bone cement leakage rate among three groups. There was statistically significant difference in postoperative vertebral body compression rate among three bone cement dispersion types( P <0.05), postoperative vertebral body compression rate in diffusion type group at 24 h postoperatively and final follow-up was (17.31±5.06)% and(18.58±4.91)%, respectively. In mixed type group, it was(14.21±5.15)% and(14.59±5.07)%, respectively. In mass type group, it was(13.89±5.02)% and(14.28±4.94)%, respectively. Bone cement dispersion type is different in PVP, PKP and manipulative reduction PVP operation. The bone cement dispersion of mass type and mixed type to recovery of compressed vertebral body is better than diffusion type, and there is no obvious difference in clinical effect in different bone cement dispersion type early and middle term.

Glycemic control and alveolar bone loss progression in type 2 diabetes.

PubMed

Taylor, G W; Burt, B A; Becker, M P; Genco, R J; Shlossman, M

1998-07-01

This study tested the hypothesis that the risk for alveolar bone loss is greater, and bone loss progression more severe, for subjects with poorly controlled (PC) type 2 diabetes mellitus (type 2 DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. The PC group had glycosylated hemoglobin (HbA1) > or = 9%; the BC group had HbA1 < 9%. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed. Of the 359 subjects, aged 15 to 57 with less than 25% radiographic bone loss at baseline, 338 did not have type 2 DM, 14 were BC, and 7 were PC. Panoramic radiographs were used to assess interproximal bone level. Bone scores (scale 0-4) corresponding to bone loss of 0%, 1% to 24%, 25% to 49%, 50% to 74%, or > or = 75% were used to identify the worst bone score (WBS) in the dentition. Change in worst bone score at follow-up, the outcome, was specified on a 4-category ordinal scale as no change, or a 1-, 2-, 3-, or 4-category increase over baseline WBS (WBS1). Poorly controlled diabetes, age, calculus, time to follow-up examination, and WBS1 were statistically significant explanatory variables in ordinal logistic regression models. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score (compared to subjects without type 2 DM) when the covariates were included in the model. The cumulative odds ratio (COR) at each threshold of the ordered response was 11.4 (95% CI = 2.5, 53.3). When contrasted with subjects with BC type 2 DM, the COR for those in the PC group was 5.3 (95% CI = 0.8, 53.3). The COR for subjects with BC type 2 DM was 2.2 (95% CI = 0.7, 6.5), when contrasted to those without type 2 DM. These results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM intermediate to the other 2 groups.

Olaparib With or Without Cediranib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

ClinicalTrials.gov

2018-06-04

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Anesthetic management with sevoflurane combined with alfaxalone-medetomidine constant rate infusion in a Thoroughbred racehorse undergoing a long-time orthopedic surgery

PubMed Central

WAKUNO, Ai; MAEDA, Tatsuya; KODAIRA, Kazumichi; KIKUCHI, Takuya; OHTA, Minoru

2017-01-01

ABSTRACT A three-year old Thoroughbred racehorse was anesthetized with sevoflurane and oxygen inhalation anesthesia combined with constant rate infusion (CRI) of alfaxalone-medetomidine for internal fixation of a third metacarpal bone fracture. After premedication with intravenous (IV) injections of medetomidine (6.0 µg/kg IV), butorphanol (25 µg/kg IV), and midazolam (20 µg/kg IV), anesthesia was induced with 5% guaifenesin (500 ml/head IV) followed immediately by alfaxalone (1.0 mg/kg IV). Anesthesia was maintained with sevoflurane and CRIs of alfaxalone (1.0 mg/kg/hr) and medetomidine (3.0 µg/kg/hr). The total surgical time was 180 min, and the total inhalation anesthesia time was 230 min. The average end-tidal sevoflurane concentration during surgery was 1.8%. The mean arterial blood pressure was maintained above 70 mmHg throughout anesthesia, and the recovery time was 65 min. In conclusion, this anesthetic technique may be clinically applicable for Thoroughbred racehorses undergoing a long-time orthopedic surgery. PMID:28955163

P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type VIA.

PubMed

Hudson, David M; Weis, MaryAnn; Rai, Jyoti; Joeng, Kyu Sang; Dimori, Milena; Lee, Brendan H; Morello, Roy; Eyre, David R

2017-03-03

Tandem mass spectrometry was applied to tissues from targeted mutant mouse models to explore the collagen substrate specificities of individual members of the prolyl 3-hydroxylase (P3H) gene family. Previous studies revealed that P3h1 preferentially 3-hydroxylates proline at a single site in collagen type I chains, whereas P3h2 is responsible for 3-hydroxylating multiple proline sites in collagen types I, II, IV, and V. In screening for collagen substrate sites for the remaining members of the vertebrate P3H family, P3h3 and Sc65 knock-out mice revealed a common lysine under-hydroxylation effect at helical domain cross-linking sites in skin, bone, tendon, aorta, and cornea. No effect on prolyl 3-hydroxylation was evident on screening the spectrum of known 3-hydroxyproline sites from all major tissue collagen types. However, collagen type I extracted from both Sc65 -/- and P3h3 -/- skin revealed the same abnormal chain pattern on SDS-PAGE with an overabundance of a γ 112 cross-linked trimer. The latter proved to be from native molecules that had intramolecular aldol cross-links at each end. The lysine under-hydroxylation was shown to alter the divalent aldimine cross-link chemistry of mutant skin collagen. Furthermore, the ratio of mature HP/LP cross-links in bone of both P3h3 -/- and Sc65 -/- mice was reversed compared with wild type, consistent with the level of lysine under-hydroxylation seen in individual chains at cross-linking sites. The effect on cross-linking lysines was quantitatively very similar to that previously observed in EDS VIA human and Plod1 -/- mouse tissues, suggesting that P3H3 and/or SC65 mutations may cause as yet undefined EDS variants. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The effect of implant design and bone quality on insertion torque, resonance frequency analysis, and insertion energy during implant placement in low or low- to medium-density bone.

PubMed

Wang, Tong-Mei; Lee, Ming-Shu; Wang, Juo-Song; Lin, Li-Deh

2015-01-01

This study investigated the effect of implant design and bone quality on insertion torque (IT), implant stability quotient (ISQ), and insertion energy (IE) by monitoring the continuous change in IT and ISQ while implants were inserted in artificial bone blocks that simulate bone of poor or poor-to-medium quality. Polyurethane foam blocks (Sawbones) of 0.16 g/cm³ and 0.32 g/cm³ were respectively used to simulate low density and low- to medium-density cancellous bone. In addition, some test blocks were laminated with a 1-mm 0.80 g/cm³ polyurethane layer to simulate cancellous bone with a thin cortical layer. Four different implants (Nobel Biocare Mk III-3.75, Mk III-4.0, Mk IV-4.0, and NobelActive-4.3) were placed into the different test blocks in accordance with the manufacturer's instructions. The IT and ISQ were recorded at every 0.5-mm of inserted length during implant insertion, and IE was calculated from the torque curve. The peak IT (PIT), final IT (FIT), IE, and final ISQ values were statistically analyzed. All implants showed increasing ISQ values when the implant was inserted more deeply. In contrast to the ISQ, implants with different designs showed dissimilar IT curve patterns during the insertion. All implants showed a significant increase in the PIT, FIT, IE, and ISQ when the test-block density increased or when the 1-mm laminated layer was present. Tapered implants showed FIT or PIT values of more than 40 Ncm for all of the laminated test blocks and for the nonlaminated test blocks of low to medium density. Parallel-wall implants did not exhibit PIT or FIT values of more than 40 Ncm for all of the test blocks. NobelActive-4.3 showed a significantly higher FIT, but a significantly lower IE, than Mk IV-4.0. While the existence of cortical bone or implant designs significantly affects the dynamic IT profiles during implant insertion, it does not affect the ISQ to a similar extent. Certain implant designs are more suitable than others if high IT is required in bone of poor quality. The manner in which IT, IE, and ISQ represent the implant primary stability requires further study.

Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage

PubMed Central

Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M

2011-01-01

Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency. PMID:21966332

Acetabular Reconstruction With Femoral Head Autograft After Intraarticular Resection of Periacetabular Tumors is Durable at Short-term Followup.

PubMed

Tang, Xiaodong; Guo, Wei; Yang, Rongli; Yan, Taiqiang; Tang, Shun; Li, Dasen

2017-12-01

Pelvic reconstruction after periacetabular tumor resection is technically difficult and characterized by a high complication rate. Although endoprosthetic replacement can result in immediate postoperative functional recovery, biologic reconstructions with autograft may provide an enhanced prognosis in patients with long-term survival; however, little has been published regarding this approach. We therefore wished to evaluate whether whole-bulk femoral head autograft that is not contaminated by tumor can be used to reconstruct segmental bone defects after intraarticular resection of periacetabular tumors. In a pilot study, we evaluated (1) local tumor control, (2) complications, and (3) postoperative function as measured by the Musculoskeletal Tumor Society score. Between 2009 and 2015, we treated 13 patients with periacetabular malignant or aggressive benign tumors with en bloc resection, bulk femoral head autograft, and cemented THA (with or without a titanium acetabular reconstruction cup), and all were included for analysis here. During that time, the general indications for this approach were (1) patients anticipated to have a good oncologic prognosis and adequate surgical margins to allow this approach, (2) patients whose pelvic bone defects did not exceed two types (Types I + II or Types II + III as defined by Enneking and Dunham), and (3) patients whose medical insurance would not cover what otherwise might have been a pelvic tumor prosthesis. During this period, another 91 patients were treated with pelvic prosthetic replacement, which was our preferred approach. Median followup in this study was 36 months (range, 24-99 months among surviving patients; one patient died 8 months after surgery); no patients were lost to followup. Bone defects were Types II + III in five patients, and Types I + II in eight. After intraarticular resection, ipsilateral femoral head autograft combined with THA was used to reconstruct the segmental bone defect of the acetabulum. In patients with Types I + II resections, the connection between the sacrum and the acetabulum was reestablished with a fibular autograft or a titanium cage filled with dried bone-allograft particles which was enhanced by using a pedicle screw and rod system. Functional evaluation was done in 11 patients who remained alive and maintained the femoral head autograft at final followup; one other patient received secondary resection involving removal of the femoral head autograft and internal fixation, and was excluded from functional evaluation. Endpoints were assessed by chart review. Two patients experienced local tumor recurrence. Finally, eight patients did not show signs of the disease, one patient died of disease for local and distant tumor relapse, and four patients survived, but still had the disease. Three of these four patients had distant metastases without local recurrence and one had local control after secondary resection but still experienced system relapse. We observed the following complications: hematoma (one patient; treated surgically with hematoma clearance), delayed wound healing (one patient; treated by débridement), deep vein thrombosis (one patient), and hip dislocation (one patient; treated with open reduction). The median 1993 Musculoskeletal Tumor Society score was 83% (25 of 30 points; range, 19-29 points), and all patients were community ambulators; one used a cane, three used a walker, and nine did not use any assistive devices. In this small series at short-term followup, we found that reconstruction of segmental bone defects after intraarticular resection of periacetabular tumors with femoral head autograft does not appear to impede local tumor control; complications were in the range of what might be expected in a series of large pelvic reconstructions, and postoperative function was generally good. Level IV, therapeutic study.

CCN3 Protein Participates in Bone Regeneration as an Inhibitory Factor*

PubMed Central

Matsushita, Yuki; Sakamoto, Kei; Tamamura, Yoshihiro; Shibata, Yasuaki; Minamizato, Tokutaro; Kihara, Tasuku; Ito, Masako; Katsube, Ken-ichi; Hiraoka, Shuichi; Koseki, Haruhiko; Harada, Kiyoshi; Yamaguchi, Akira

2013-01-01

CCN3, a member of the CCN protein family, inhibits osteoblast differentiation in vitro. However, the role of CCN3 in bone regeneration has not been well elucidated. In this study, we investigated the role of CCN3 in bone regeneration. We identified the Ccn3 gene by microarray analysis as a highly expressed gene at the early phase of bone regeneration in a mouse bone regeneration model. We confirmed the up-regulation of Ccn3 at the early phase of bone regeneration by RT-PCR, Western blot, and immunofluorescence analyses. Ccn3 transgenic mice, in which Ccn3 expression was driven by 2.3-kb Col1a1 promoter, showed osteopenia compared with wild-type mice, but Ccn3 knock-out mice showed no skeletal changes compared with wild-type mice. We analyzed the bone regeneration process in Ccn3 transgenic mice and Ccn3 knock-out mice by microcomputed tomography and histological analyses. Bone regeneration in Ccn3 knock-out mice was accelerated compared with that in wild-type mice. The mRNA expression levels of osteoblast-related genes (Runx2, Sp7, Col1a1, Alpl, and Bglap) in Ccn3 knock-out mice were up-regulated earlier than those in wild-type mice, as demonstrated by RT-PCR. Bone regeneration in Ccn3 transgenic mice showed no significant changes compared with that in wild-type mice. Phosphorylation of Smad1/5 was highly up-regulated at bone regeneration sites in Ccn3 KO mice compared with wild-type mice. These results indicate that CCN3 is up-regulated in the early phase of bone regeneration and acts as a negative regulator for bone regeneration. This study may contribute to the development of new strategies for bone regeneration therapy. PMID:23653360

Injection of Unicameral Bone Cysts with Bone Marrow Aspirate and Demineralized Bone Matrix Avoids Open Curettage and Bone Grafting in a Retrospective Cohort.

PubMed

Gundle, Kenneth R; Bhatt, Etasha M; Punt, Stephanie E; Bompadre, Viviana; Conrad, Ernest U

2017-01-01

Many treatment options exist for unicameral bone cysts (UBC), without clear evidence of superiority. Meta-analyses have been limited by small numbers of patients in specific anatomic and treatment subgroups. The purpose of this study was to report the outcomes of injecting bone marrow aspirate and demineralized bone matrix (BMA/DBM) for the treatment of proximal humerus UBC. Fifty-one patients with proximal humerus lesions treated by BMA/DBM injection were retrospectively reviewed from a single academic medical center. The mean number of injections performed per patient was 2.14 (range 1-5). Eleven patients underwent only one injection (22%), an additional 19 patients completed treatment after two injections (37%), four patients healed after three injections (8%), and one patient healed after four injections (2%). The cumulative success rate of serial BMA/DBM injections was 22% (11/51), 58% (30/51), 67% (34/51), and 69% (35/51). Eleven patients (22%) ultimately underwent open curettage and bone grafting, and five patients (10%) were treated with injection of calcium phosphate bone substitute. A BMA/DBM injection strategy avoided an open procedure in 78% of patients with a proximal humerus UBC. The majority of patients underwent at least 2 injection treatments. Level IV retrospective cohort study.

Sex differences in the pharmacokinetics of recombinant human granulocyte colony-stimulating factor in the rat.

PubMed

Tanaka, H; Kaneko, T

1991-01-01

The pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were studied in male and female rats. The serum concentration of rhG-CSF after iv and sc administration to male and female Sprague-Dawley rats at a dose of 5 and 100 micrograms/kg was investigated by a sandwich enzyme-linked immunosorbent assay. After iv administration, AUC and half-lives of rhG-CSF in female rats were smaller than those for male rats. The volume of distribution of rhG-CSF in female rats was not significantly different from that in male rats. After sc administration, AUC, mean residence time, and half-lives of elimination phase in female rats were smaller than those for male rats. The in vitro biological activities of rhG-CSF were investigated using [3H]thymidine uptake assay in cultures of bone marrow cells obtained from male and female rat femur. Female rat bone marrow cells showed a similar dose-response profile to rhG-CSF to that of male rat bone marrow cells. The effect of rhG-CSF administration in rats was a specific activity on the neutrophil lineage with an increase of neutrophils in peripheral blood. The in vivo effects of rhG-CSF after iv and sc administration to male and female rats at 5 and 100 micrograms/kg doses were determined. After 100 micrograms/kg administration, the neutrophil count in female rats was similar to that in male rats in the early period; however, the neutrophil count in female rats was lower than that in male rats 24 hr after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of the bone injection gun in the treatment of organophosphate poisoning.

PubMed

Eisenkraft, Arik; Gilat, Eran; Chapman, Shira; Baranes, Shlomo; Egoz, Inbal; Levy, Aharon

2007-04-01

Immediate administration of antidotal treatment is crucial in severe organophosphate (OP) poisoning and the use of an open intravenous (i.v.) line might also be required. The state of casualties might prevent getting access to their veins. The bone injection gun (BIG) was established as a simple method for introducing an intraosseous (i.o.) line and could be applied while wearing a protective suit. The present study followed the pharmacokinetics of the anticonvulsive drug midazolam after i.o. administration in pigs compared with i.v. and the common intramuscular (i.m.) administration. A new method for monitoring midazolam concentrations in plasma was developed. Plasma concentrations following both i.v. and i.o. administrations peaked at 2 min post injection and only at 10 min following the i.m. route. In an antidotal treatment study against paraoxone poisoning, the anticonvulsive effect of midazolam appeared immediately following i.o. administration, while it took 5-10 min to exhibit a similar effect following i.m. administration. This study indicates that the use of i.o. administration after OP poisoning might provide the necessary fast response for rapid termination of convulsions. The BIG might offer a convenient method for treating casualties in the chemical arena by teams wearing full protective gear. Copyright (c) 2007 John Wiley & Sons, Ltd.

Short wavelength infrared optical windows for evaluation of benign and malignant tissues

NASA Astrophysics Data System (ADS)

Sordillo, Diana C.; Sordillo, Laura A.; Sordillo, Peter P.; Shi, Lingyan; Alfano, Robert R.

2017-04-01

There are three short wavelength infrared (SWIR) optical windows outside the conventionally used first near-infrared (NIR) window (650 to 950 nm). They occur in the 1000- to 2500-nm range and may be considered second, third, and fourth NIR windows. The second (1100 to 1350 nm) and third windows (1600 to 1870 nm) are now being explored through label-free linear and multiphoton imaging. The fourth window (2100 to 2350 nm) has been mostly ignored because of water absorption and the absence of sensitive detectors and ultrafast lasers. With the advent of new technology, use of window IV is now possible. Absorption and scattering properties of light through breast and prostate cancer, bone, lipids, and intralipid solutions at these windows were investigated. We found that breast and prostate cancer and bone have longer total attenuation lengths at NIR windows III and IV, whereas fatty tissues and intralipid have longest lengths at windows II and III. Since collagen is the major chromophore at 2100 and 2350 nm, window IV could be especially valuable in evaluating cancers and boney tissues, whereas windows II and III may be more useful for tissues with high lipid content. SWIR windows may be utilized as additional optical tools for the evaluation of collagen in tissues.

Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

PubMed Central

Woodburn, Kathryn W.; Holmes, Christopher P.; Wilson, Susan D.; Fong, Kei-Lai; Press, Randall J.; Moriya, Yuu; Tagawa, Yoshihiko

2011-01-01

The pharmacokinetics(PK) (absorption, distribution, metabolism, excretion) of peginesatide.a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA), was evaluated in rats. The PK profile was evaluated at 0.1-5 mg·kg−1 IV using unlabeled or [14C]-labeled peginesatide. Mass balance, tissue distribution and metabolism were evaluated following IV administration of 5 mg·kg−1 [14C]-peginesatide, with tissue distribution also evaluated by quantitative whole-body autoradiography (QWBA) following an IV dose of 17 mg·kg−1[14C]-peginesatide. Plasma clearance was slow and elimination was biphasic with unchanged peginesatide representing >90% of the total radioactivity of the total radioactive exposure. Slow uptake of the radiolabeled compound from the vascular compartment into the tissues was observed. Biodistribution to bone marrow and extramedullary hematopoietic sites, and to highly vascularized lymphatic and excretory tissues occurred. A predominant degradation event to occur in vivo was the loss of one PEG chain from the branched PEG moiety to generate mono-PEG. Renal excretion was the primary mechanism (41%) of elimination, with parent molecule (67%) the major moiety excreted. In conclusion, elimination of [14C]-peginesatide-derived radioactivity was extended, retention preferentially occurred at sites of erythropoiesis (bone marrow), and urinary excretion was the primary elimination route. PMID:22188389

Short wavelength infrared optical windows for evaluation of benign and malignant tissues.

PubMed

Sordillo, Diana C; Sordillo, Laura A; Sordillo, Peter P; Shi, Lingyan; Alfano, Robert R

2017-04-01

There are three short wavelength infrared (SWIR) optical windows outside the conventionally used first near-infrared (NIR) window (650 to 950 nm). They occur in the 1000- to 2500-nm range and may be considered second, third, and fourth NIR windows. The second (1100 to 1350 nm) and third windows (1600 to 1870 nm) are now being explored through label-free linear and multiphoton imaging. The fourth window (2100 to 2350 nm) has been mostly ignored because of water absorption and the absence of sensitive detectors and ultrafast lasers. With the advent of new technology, use of window IV is now possible. Absorption and scattering properties of light through breast and prostate cancer, bone, lipids, and intralipid solutions at these windows were investigated. We found that breast and prostate cancer and bone have longer total attenuation lengths at NIR windows III and IV, whereas fatty tissues and intralipid have longest lengths at windows II and III. Since collagen is the major chromophore at 2100 and 2350 nm, window IV could be especially valuable in evaluating cancers and boney tissues, whereas windows II and III may be more useful for tissues with high lipid content. SWIR windows may be utilized as additional optical tools for the evaluation of collagen in tissues.

Correlating the nanoscale mechanical and chemical properties of knockout mice bones

NASA Astrophysics Data System (ADS)

Kavukcuoglu, Nadire Beril

Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2-/- bones had significantly lower hardness and elastic modulus compared to Fbn2+/+ bones, but the crystallinity was higher. Type-B carbonate substitution decreased significantly in OC-/- and Fbn2-/- bones compared to their wild-type controls. The thesis has provided new insight into how non-collagenous proteins affect the nanomechanics and chemistry of bone tissue. This information will assist in the development of new treatments for osteopenia/osteoporosis.

[Alterations of bone metabolism in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2011-01-01

Diabetes mellitus type 1 is one of the most common chronic diseases in children and adolescents. The incidence of diabetes mellitus type 1 is increasing rapidly worldwide. Recently, the largest rate of increase is observed in children aged 0-4 years. Chronic hyperglycemia leads to microvascular and macrovascular complications including retinopathy, nephropathy, neuropathy and cardiomyopathy. Pathological changes occur in the bone structure. The lack of diagnosis and treatment of alterations of the bone tIssue metabolism may lead to osteoporosis, which is characterized by much reduced bone mineral density and changes in the microarchitecture of the bone tIssue, which in consequence results in increased susceptibility to fractures. Diabetes mellitus type 1 most often starts before achieving peak bone mass, which constitutes a point of reference for predicting risk of fractures in a later period of life. Mechanisms responsible for loss of the bone tIssue in diabetes of type 1 still remain unexplained. Many research findings indicate the anabolic role of insulin and insulin-like growth factors, mainly IGF-1. The aim of this manuscript is to review recent papers about alterations of bone metabolism in children and adolescents with diabetes mellitus type 1.

Nurse exposure doses resulted from bone scintigraphy patient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tunçman, Duygu, E-mail: duygutuncman@gmail.com; Demir, Bayram; Kovan, Bilal

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It’s general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget’s disease, investigation of loosening and infection in orthopedic implants. It is applied with using {sup 99m}Tc labeled radiopharmaceuticals (e.g {sup 99m} Tc MDP,{sup 99m}Tc HEDP and {sup 99m}Tc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. Whenmore » some patient’s situation is not good, patients are hospitalized until the scanning because of patients’ close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse’s exposure radiations from patient’s routine treatment, examination and emergency station.« less

Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I.

PubMed

Halling Linder, Cecilia; Enander, Karin; Magnusson, Per

2016-03-01

Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein-protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

Risk factors for late-onset neutropenia after rituximab treatment of B-cell lymphoma.

PubMed

Arai, Yasuyuki; Yamashita, Kouhei; Mizugishi, Kiyomi; Nishikori, Momoko; Hishizawa, Masakatsu; Kondo, Tadakazu; Kitano, Toshiyuki; Kawabata, Hiroshi; Kadowaki, Norimitsu; Takaori-Kondo, Akifumi

2015-05-01

Late-onset neutropenia after rituximab (RTX) therapy (R-LON) has been widely reported, but clinical studies on a large number of cases are limited. In this study, we aimed to investigate the incidence and risk factors of R-LON. In this study, we retrospectively analyzed data of 213 enrolled B-cell lymphoma patients (male 114; female 99) treated with RTX at a single institution. R-LON was defined as otherwise unexplained grade III-IV neutropenia after RTX. The median age of the patients was 62 years, and 129 of them were initially diagnosed at advanced stages (stage III-IV). R-LON occurred in 19 patients within a median of 121 (range, 49-474) days after the last RTX administration. The 1-year cumulative incidence was 9.0%. On univariate analysis, older age (>60 years), advanced stage, and purine analog or methotrexate administration were significant or borderline significant risk factors for R-LON, whereas sex, disease type, bone marrow invasion, combination with cytotoxic chemotherapeutic drugs, intensified therapy (compared with R-CHOP), prior autologous transplantation, and repeated RTX administration were not. On multivariate analysis, older age (hazard ratio (HR), 2.95) and advanced stage (HR, 3.56) were significant risk factors. Treatment with granulocyte colony-stimulating factor was feasible in grade IV R-LON patients with high risk of infection. Careful follow-up is therefore necessary after B-cell lymphoma treatment, especially in high-risk patients with advanced disease or of older age.

[Bone turnover in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2013-01-01

Biochemical bone turnover markers are fragments of protein structural elements of the bone created during the synthesis or degradation and enzymes specific for bone cells, released into the circulation during the metabolic activity of osteoblasts and osteoclasts. Bone turnover markers are used as indicators to evaluate the activity of modeling and remodeling processes. They are the result of the activity of all remodeling processes taking place at the moment in the whole skeleton. The assay allows quick assessment of the rate of bone formation and resorption processes. Among many complications in children with type 1 diabetes increased bone turnover leading to a reduction in bone mass may increase the risk of osteopenia or osteoporosis in adulthood. The aim of this manuscript is to review recent papers about bone turnover in children and adolescents with diabetes mellitus type 1.

Temporary arthrodesis using fixator rods in two-stage revision of septic knee prothesis with severe bone and tissue defects.

PubMed

Röhner, Eric; Pfitzner, Tilman; Preininger, Bernd; Zippelius, Timo; Perka, Carsten

2016-01-01

The present study describes a new temporary arthrodesis procedure, which aims for septic knee prosthesis replacement, in particular for larger bone and soft tissue defects. Our technique offers high stability and full weight-bearing capacity of the knee joint. The study included 16 patients with major bone defects (AORI type IIb or greater) after receiving a radical debridement and a septic two-stage revision total knee arthroplasty. After removing the infected prosthesis and debridement, two AO fixator rods were positioned into the intramedullary space of the femur and tibia. Subsequently, both rods were joined tube-to-tube and adjusted in the center of the knee joint. Finally, the whole cavity of the knee joint was filled with PMMA. The number of previous surgeries, bacterial spectrum, risk factors for further infection and reinfection rates was recorded. Immediately after the temporary arthrodesis, radiographs of the knee with the enclosed spacers were taken in order to compare to previous radiographs and avoiding to miss possible spacer loosening. Nine of sixteen patients underwent more than two revision surgeries before receiving our new arthrodesis technique. No cases of spacer loosening were observed in all 16 patients; further, there were no peri-implant fractures, and four persistent infections were noted. Temporary arthrodesis using AO fixator rods offers a high stability without loosening. Its potential to replace conventional augmentation techniques should be taken into account, particularly in the case of larger bone and tissue defects. In clinical practice, the cemented spacer using AO fixator rods could be an alternative technique for temporary knee arthrodesis after septic debridement. Retrospective case series, Level IV.

Complex craniofacial advancement in paediatric patients: Piezoelectric and traditional technique evaluation.

PubMed

Spinelli, Giuseppe; Mannelli, Giuditta; Zhang, Yi Xin; Lazzeri, Davide; Spacca, Barbara; Genitori, Lorenzo; Raffaini, Mirco; Agostini, Tommaso

2015-10-01

The piezoelectric device allows bone cutting without damaging the surrounding soft tissues. The purpose of this study was to assess the role of this surgical instrument in paediatric craniofacial surgery in terms of safety and surgical outcomes. Thirteen consecutive paediatric patients underwent craniofacial Le Fort osteotomies type III and IV. The saw was used on the right side in seven patients and on the left side in six patients; the piezoelectric instrument was used on the right side in six patients and on the left side in seven patients. Intraoperative blood loss, surgical procedure length, incision precision, postoperative haematoma and swelling, and nerve impairment were evaluated to compare the outcomes of both procedures. A longer surgical procedure was observed in 28% of the patients when using the piezoelectric device (p = 0.032), with an intraoperative blood loss reduction of 18% (p = 0.156). Greater precision in bone cutting was reported, together with a reduction in the requirement to protect and incise adjacent soft tissues during piezoelectric osteotomies. There was a lower incidence of postoperative haematoma and swelling following piezo-osteotomy, and a significant reduction in postoperative nerve impairment (p = 0.002). The ultrasonic surgical device guaranteed a clean bone cut, preserving the integrity of the adjacent soft tissues beneath the bone. Although the time required for a piezoelectric osteotomy was longer, the total operation time remained approximately the same. In conclusion, the device's lack of power appears to be a minor problem compared with the advantages, and an ultrasonic device could be considered a valuable instrument for paediatric craniofacial advancement. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

42 CFR 494.110 - Condition: Quality assessment and performance improvement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... improvement. 494.110 Section 494.110 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... RENAL DISEASE FACILITIES Patient Care § 494.110 Condition: Quality assessment and performance... renal bone disease. (iv) Anemia management. (v) Vascular access. (vi) Medical injuries and medical...

42 CFR 494.110 - Condition: Quality assessment and performance improvement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... improvement. 494.110 Section 494.110 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... RENAL DISEASE FACILITIES Patient Care § 494.110 Condition: Quality assessment and performance... renal bone disease. (iv) Anemia management. (v) Vascular access. (vi) Medical injuries and medical...

42 CFR 494.110 - Condition: Quality assessment and performance improvement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... improvement. 494.110 Section 494.110 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... RENAL DISEASE FACILITIES Patient Care § 494.110 Condition: Quality assessment and performance... renal bone disease. (iv) Anemia management. (v) Vascular access. (vi) Medical injuries and medical...

Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

ClinicalTrials.gov

2018-01-22

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Metastatic Prostatic Adenocarcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage III Prostate Adenocarcinoma; Stage IV Prostate Adenocarcinoma

The role of midazolam-induced sedation in bone marrow aspiration/trephine biopsies.

PubMed

Mainwaring, C J; Wong, C; Lush, R J; Smith, J G; Singer, C R

1996-12-01

This study was undertaken in 102 adult patients to evaluate the safety and efficacy of intravenous (i.v.) midazolam in the setting of bone marrow aspiration and trephine biopsy (BMAT). Combined local anaesthetic (LA) and sedation was used in 87% of patients and 13% received LA alone. Amnesia occurred in all sedated patients with only 9% experiencing a mild degree of post-procedure pain. This contrasted sharply with the non-sedated group, in whom 85% had intense pain during the biopsy followed by protracted local discomfort in approximately 54%. Drowsiness and some psychomotor impairment were the only notable sedation-related side-effects in approximately 20%. None required assisted ventilation. There was a resounding patient preference for BMAT with sedation. Considering the ease of use, safety and efficacy of i.v. midazolam, the availability of flumazenil as a reversal agent and the undoubted positive effects on quality of life, we would advocate using it in BMAT provided that there were no contraindications.

Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

PubMed

Windahl, Sara H; Andersson, Niklas; Börjesson, Anna E; Swanson, Charlotte; Svensson, Johan; Movérare-Skrtic, Sofia; Sjögren, Klara; Shao, Ruijin; Lagerquist, Marie K; Ohlsson, Claes

2011-01-01

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

Reduced Bone Mass and Muscle Strength in Male 5α-Reductase Type 1 Inactivated Mice

PubMed Central

Windahl, Sara H.; Andersson, Niklas; Börjesson, Anna E.; Swanson, Charlotte; Svensson, Johan; Movérare-Skrtic, Sofia; Sjögren, Klara; Shao, Ruijin; Lagerquist, Marie K.; Ohlsson, Claes

2011-01-01

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1−/− mice. Four-month-old male Srd5a1 −/− mice had reduced trabecular bone mineral density (−36%, p<0.05) and cortical bone mineral content (−15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1 −/− mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1 −/− mice. Male Srd5a1 −/− mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1 −/− mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1 −/− mice, is an indirect effect mediated by elevated circulating androgen levels. PMID:21731732

Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

PubMed

Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

2016-09-01

Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of various diagnostic methods in a patient with Gaucher disease type I.

PubMed

Farahati, J; Trenn, G; John-Mikolajewski, V; Zander, C; Pastores, G M; Sciuk, J; Reiners, C

1996-08-01

A series of plain radiographs, bone scans, bone marrow scans, and MRIs is reported in a patient with Gaucher disease type I, in whom two episodes of acute bone crisis developed during a 6-year period of follow-up. Acute bone crisis and global indolent bone marrow displacement could both be assessed by bone marrow scintigraphy, whereas MRI could better clarify the corti-comedullary alteration after bone infarction. Thus, MRI and bone marrow scintigraphy could be used as complementary imaging methods in the management of patients with Gaucher disease.

Consensus in controversy: The modified Delphi method applied to Gynecologic Oncology practice.

PubMed

Cohn, David E; Havrilesky, Laura J; Osann, Kathryn; Lipscomb, Joseph; Hsieh, Susie; Walker, Joan L; Wright, Alexi A; Alvarez, Ronald D; Karlan, Beth Y; Bristow, Robert E; DiSilvestro, Paul A; Wakabayashi, Mark T; Morgan, Robert; Mukamel, Dana B; Wenzel, Lari

2015-09-01

To determine the degree of consensus regarding the probabilities of outcomes associated with IP/IV and IV chemotherapy. A survey was administered to an expert panel using the Delphi method. Ten ovarian cancer experts were asked to estimate outcomes for patients receiving IP/IV or IV chemotherapy. The clinical estimates were: 1) probability of completing six cycles of chemotherapy, 2) probability of surviving five years, 3) median survival, and 4) probability of ER/hospital visits during treatment. Estimates for two patients, one with a low comorbidity index (patient 1) and the other with a moderate index (patient 2), were included. The survey was administered in three rounds, and panelists could revise their subsequent responses based on review of the anonymous opinions of their peers. The ranges were smaller for IV compared with IP/IV therapy. Ranges decreased with each round. Consensus converged around outcomes related to IP/IV chemotherapy for: 1) completion of 6 cycles of therapy (type 1 patient, 62%, type 2 patient, 43%); 2) percentage of patients surviving 5 years (type 1 patient, 66%, type 2 patient, 47%); and 3) median survival (type 1 patient, 83 months, type 2 patient, 58 months). The group required three rounds to achieve consensus on the probabilities of ER/hospital visits (type 1 patient, 24%, type 2 patient, 35%). Initial estimates of survival and adverse events associated with IP/IV chemotherapy differ among experts. The Delphi process works to build consensus and may be a pragmatic tool to inform patients of their expected outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Change in genotype of methicillin-resistant Staphylococcus aureus (MRSA) affects the antibiogram of hospital-acquired MRSA.

PubMed

Harada, Dai; Nakaminami, Hidemasa; Miyajima, Eri; Sugiyama, Taku; Sasai, Nao; Kitamura, Yoshinobu; Tamura, Taku; Kawakubo, Takashi; Noguchi, Norihisa

2018-07-01

Recently, the dissemination of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) into hospitals has frequently been reported worldwide. Hospital-acquired MRSA (HA-MRSA) strains exhibit high-level resistance to multiple antimicrobial agents, whereas CA-MRSA strains are usually susceptible to non-β-lactams. Thus, it is predicted that the antibiogram of the HA-MRSA population would change along with the change in genotype of MRSA. Here, we investigated the changes in the MRSA population along with the MRSA antibiogram in a hospital between 2010 and 2016. Staphylococcal cassette chromosome (SCC) mec typing showed that the predominant HA-MRSA strains in the hospital dramatically changed from SCCmec type II, which is the major type of HA-MRSA, to SCCmec type IV, which is the major type of CA-MRSA. Multilocus sequence typing revealed that the predominant SCCmec type IV strain was a clonal complex (CC) 8 clone, which is mainly found among CA-MRSA. Furthermore, the CC1-SCCmec type IV (CC1-IV) clone significantly increased. Both the CC8-IV and CC1-IV clones exhibited high antimicrobial susceptibility. The antibiogram change of the HA-MRSA population was consistent with the antimicrobial susceptibilities and increased prevalence of the CC8-IV and CC1-IV clones. Our data reveal that the change in the genotypes of MRSA strains could impact the antibiogram of HA-MRSA population. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

As solid as a rock-comparison of CE- and MPS-based analyses of the petrosal bone as a source of DNA for forensic identification of challenging cranial bones.

PubMed

Kulstein, Galina; Hadrys, Thorsten; Wiegand, Peter

2018-01-01

Short tandem repeat (STR) typing from skeletal remains can be a difficult task. Dependent on the environmental conditions of the provenance of the bones, DNA can be degraded and STR typing inhibited. Generally, dense and compact bones are known to preserve DNA better. Several studies already proved that femora and teeth have high DNA typing success rates. Unfortunately, these elements are not present in all cases involving skeletal remains. Processing partial or singular skeletal elements, it is favorable to select bone areas where DNA preservation is comparably higher. Especially, cranial bones are often accidentally discovered during criminal investigations. The cranial bone is composed of multiple parts. In this examination, we evaluated the potential of the petrous bone for human identification of skeletal remains in forensic case work. Material from different sections of eight unknown cranial bones and-where available-additionally other skeletal elements, collected at the DNA department of the Institute of Legal Medicine in Ulm, Germany, from 2010 to 2017, were processed with an optimized DNA extraction and STR typing strategy. The results highlight that STR typing from the petrous bones leads to reportable profiles in all individuals, even in cases where the analysis of the parietal bone failed. Moreover, the comparison of capillary electrophorese (CE) typing to massively parallel sequencing (MPS) analysis shows that MPS has the potential to analyze degraded human remains and is even capable to provide additional information about phenotype and ancestry of unknown individuals.

Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis

DTIC Science & Technology

2014-06-01

Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis PRINCIPAL INVESTIGATOR...Award Number: W81XWH-13-1-0113 TITLE: Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin...31 May 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta

Trapezium Bone Density-A Comparison of Measurements by DXA and CT.

PubMed

Breddam Mosegaard, Sebastian; Breddam Mosegaard, Kamille; Bouteldja, Nadia; Bæk Hansen, Torben; Stilling, Maiken

2018-01-18

Bone density may influence the primary fixation of cementless implants, and poor bone density may increase the risk of implant failure. Before deciding on using total joint replacement as treatment in osteoarthritis of the trapeziometacarpal joint, it is valuable to determine the trapezium bone density. The aim of this study was to: (1) determine the correlation between measurements of bone mineral density of the trapezium obtained by dual-energy X-ray absorptiometry (DXA) scans by a circumference method and a new inner-ellipse method; and (2) to compare those to measurements of bone density obtained by computerized tomography (CT)-scans in Hounsfield units (HU). We included 71 hands from 59 patients with a mean age of 59 years (43-77). All patients had Eaton-Glickel stage II-IV trapeziometacarpal (TM) joint osteoarthritis, were under evaluation for trapeziometacarpal total joint replacement, and underwent DXA and CT wrist scans. There was an excellent correlation (r = 0.94) between DXA bone mineral density measures using the circumference and the inner-ellipse method. There was a moderate correlation between bone density measures obtained by DXA- and CT-scans with (r = 0.49) for the circumference method, and (r = 0.55) for the inner-ellipse method. DXA may be used in pre-operative evaluation of the trapezium bone quality, and the simpler DXA inner-ellipse measurement method can replace the DXA circumference method in estimation of bone density of the trapezium.

Role of clinician's experience and implant design on implant stability. An ex vivo study in artificial soft bones.

PubMed

Romanos, Georgios E; Basha-Hijazi, Abdulaziz; Gupta, Bhumija; Ren, Yan-Fang; Malmstrom, Hans

2014-04-01

Clinical experience in implant placement is important in order to prevent implant failures. However, the implant design affects the primary implant stability (PS) especially in poor quality bones. Therefore, the aim of this study was to compare the effect of clinician surgical experience on PS, when placing different type of implant designs. A total of 180 implants (90 parallel walled-P and 90 tapered-T) were placed in freshly slaughtered cow ribs. Bone quality was evaluated by two examiners during surgery and considered as 'type IV' bone. Implants (ø 5 mm, length: 15 mm, Osseotite, BIOMET 3i, Palm Beach Gardens, FL, USA) were placed by three different clinicians (master/I, good/II, non-experienced/III, under direct supervision of a manufacturer representative; 30 implants/group). An independent observer assessed the accuracy of placement by resonance frequency analysis (RFA) with implant stability quotient (ISQ) values. Two-way analysis of variance (ANOVA) and Tukey's post hoc test were used to detect the surgical experience of the clinicians and their interaction and effects of implant design on the PS. All implants were mechanically stable. The mean ISQ values were: 49.57(± 18.49) for the P-implants and 67.07(± 8.79) for the T-implants. The two-way ANOVA showed significant effects of implant design (p < .0001), clinician (p < .0001), and their interaction (p < .0001). The Tukey's multiple comparison test showed significant differences in RFA for the clinician group I/II (p = .015) and highly significant (p < .0001) between I/III and II/III. The P-implants presented (for I, II, and III) mean ISQ values 31.25/49.18/68.17 and the T-implants showed higher ISQ values, 70.15/62.08/68.98, respectively. Clinicians I and II did not show extreme differences for T-implants (p = .016). In contrast, clinician III achieved high ISQ values using P- and T-implants following the exact surgical protocol based on the manufacturer guidelines. T-implants provided high stability for experienced clinicians compared with P-implants. T-implants achieved greater PS than the P-implants. All clinicians consistently achieved PS; however, experienced clinicians achieved higher ISQ values with T-implants in poor quality bone. © 2012 Wiley Periodicals, Inc.

Differential expression of basement membrane type IV collagen α2 and α6 chains as a prognostic factor in patients with extrahepatic bile duct carcinoma.

PubMed

Hirashima, Kotaro; Iyama, Ken-Ichi; Baba, Yoshifumi; Honda, Yumi; Sado, Yoshikazu; Ninomiya, Yoshifumi; Watanabe, Masayuki; Takamori, Hiroshi; Beppu, Toru; Baba, Hideo

2013-03-01

The destruction of the basement membrane (BM) is the first step in cancer invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct α(IV) chains; α1(IV) to α6(IV). The loss of α5(IV) and α6(IV) chains from the epithelial BM at the early stage of cancer invasion has been reported in several types of cancers. However, the expression of α5(IV) and α6(IV) chains in extrahepatic bile duct carcinoma (EBDC) remains unclear. We examined the expression of α(IV) chains by immunohistochemistry using 71 resected EBDC specimens. Prognostic significance of α(IV) chains was examined by Cox regression and Kaplan-Meier analyses. In the invasive cancer, the expression of α6(IV) chain in the BM was lost partially or completely preceded by the loss of α2(IV) chain. The loss of α6(IV) chain in the BM of the invasive cancer was related to the tumor classification, TNM stages, and the expression of α2(IV) chain. The patients with α2(IV)-negative and α6(IV)-negative chains had significantly poorer prognosis than those with α2(IV)-positive and α6(IV)-positive/negative chains (P = 0.04). The loss of α2(IV) and α6(IV) chains might be a useful prognostic factor in patients with EBDC. Copyright © 2012 Wiley Periodicals, Inc.

Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

PubMed

Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

1987-08-01

Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy.

Pulp regeneration after non-infected and infected necrosis, what type of tissue do we want? A review.

PubMed

Andreasen, Jens O; Bakland, Leif K

2012-02-01

Regeneration (revitalization) of infected necrotic pulp tissue has been an important issue in endodontics for more than a decade. Based on a series of case reports, there appears to be evidence that new soft tissue can enter the root canal with a potential for subsequent hard tissue deposition resulting in a narrowing of the root canal. Very little is presently known about the exact nature of this tissue growing into the canal and how it may behave in the long term. In the case of regeneration of necrotic non-infected pulp tissue, a series of clinical and histological studies have shown that such events may take place in four variants: (i) Revascularization of the pulp with accelerated dentin formation leading to pulp canal obliteration. This event has a good long-term prognosis. (ii) Ingrowth of cementum and periodontal ligament (PDL). The long-term prognosis for this event is not known. (iii) Ingrowth of cementum, PDL, and bone. The long-term prognosis is only partly known, but cases developing an internal ankylosis have been described. (iv) Ingrowth of bone and bone marrow is a rare phenomenon and the long-term prognosis does not appear to be good. Based on current knowledge, expectations with respect to pulp regeneration (revitalization) of infected necrotic dental pulps are difficult to predict; more information than now available is needed before procedures for pulpal regeneration can be routinely recommended with a predictable long-term prognosis. © 2011 John Wiley & Sons A/S.

The role of Shewanella oneidensis MR-1 outer surface structures in extracellular electron transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bouhenni, Rachida; Vora, Gary J.; Biffinger, Justin C.

2010-04-20

Shewanella oneidensis is a facultative anaerobe that uses more than 14 different terminal electron acceptors for respiration. These include metal oxides and hydroxyoxides, and toxic metals such as uranium and chromium. Mutants deficient in metal reduction were isolated using the mariner transposon derivative, minihimar RB1. These included mutants with transposon insertions in the prepilin peptidase and type II secretion system genes. All mutants were deficient in Fe(III) and Mn(IV) reduction, and exhibited slow growth when DMSO was used as the electron acceptor. The genome sequence of S. oneidensis contains one prepilin peptidase gene, pilD. A similar prepilin peptidase that maymore » function in the processing of type II secretion prepilins was not found. Single and multiple chromosomal deletions of four putative type IV pilin genes did not affect Fe(III) and Mn(IV) reduction. These results indicate that PilD in S. oneidensis is responsible for processing both type IV and type II secretion prepilin proteins. Type IV pili do not appear to be required for Fe(III) and Mn(IV) reduction.« less

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

PubMed

Govey, Peter M; Zhang, Yue; Donahue, Henry J

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Basement membrane of mouse bone marrow sinusoids shows distinctive structure and proteoglycan composition: a high resolution ultrastructural study.

PubMed

Inoue, S; Osmond, D G

2001-11-01

Venous sinusoids in bone marrow are the site of a large-scale traffic of cells between the extravascular hemopoietic compartment and the blood stream. The wall of the sinusoids consists solely of a basement membrane interposed between a layer of endothelial cells and an incomplete covering of adventitial cells. To examine its possible structural specialization, the basement membrane of bone marrow sinusoids has now been examined by high resolution electron microscopy of perfusion-fixed mouse bone marrow. The basement membrane layer was discontinuous, consisting of irregular masses of amorphous material within a uniform 60-nm-wide space between apposing endothelial cells and adventitial cell processes. At maximal magnifications, the material was resolved as a random arrangement of components lacking the "cord network" formation seen in basement membranes elsewhere. Individual components exhibited distinctive ultrastructural features whose molecular identity has previously been established. By these morphological criteria, the basement membrane contained unusually abundant chondroitin sulfate proteoglycan (CSPG) revealed by 3-nm-wide "double tracks," and moderate amounts of both laminin as dense irregular coils and type IV collagen as 1-1.5-nm-wide filaments, together with less conspicuous amounts of amyloid P forming pentagonal frames. In contrast, 4.5-5-nm-wide "double tracks" characteristic of heparan sulfate proteoglycan (HSPG) were absent. The findings demonstrate that, in comparison with "typical" basement membranes in other tissues, the bone marrow sinusoidal basement membrane is uniquely specialized in several respects. Its discontinuous nature, lack of network organization, and absence of HSPG, a molecule that normally helps to maintain membrane integrity, may facilitate disassembly and reassembly of basement membrane material in concert with movements of adventitial cell processes as maturing hemopoietic cells pass through the sinusoidal wall: the exceptionally large quantity of CSPG may represent a reservoir of CD44 receptor for use in hemopoiesis. Copyright 2001 Wiley-Liss, Inc.

Non-invasive photo acoustic approach for human bone diagnosis.

PubMed

Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

2016-12-01

The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via IR sensors, and acoustic wave signals may be detected via sensitive pressure transducer, which is reserved for future realization.

Locking plate and fibular strut-graft augmentation in the reconstruction of unicameral bone cyst of proximal femur in the paediatric population.

PubMed

Jamshidi, Khodamorad; Mirkazemi, Masoud; Izanloo, Azra; Mirzaei, Alireza

2018-01-01

Several therapeutic strategies have been used for managing unicameral bone cyst (UBC) of the proximal femur. However, there is insufficient evidence to support one treatment over another, and the optimal treatment is controversial. This study aims at describing our experience with surgical reconstruction of paediatric UBCs of the proximal femur using a proximal locking plate and fibular strut allograft. In total, 14 consecutive paediatric patients with Dormans types IB (four cases) and IIB (10 cases) UBC were assessed. Mean patient age was 8.6 ± 2.3 years, and mean follow-up period was 41.7 ± 29.8 months. Six patients (42.8%) were referred with a pathologic fracture. Clinical/radiological outcome and complication rates were evaluated at the final follow-up session. No cysts were Capanna's class III (recurrence) or IV (no response). Complete healing (Capanna's class I) was seen in ten cysts, while four other cysts healed with residual radiolucent areas (Capanna's class II). Mean healing period was 14.1 ± 5.1 (9-24 months). One patient had superficial infection, one heterotopic ossification, and one mild coxa vara, and mean Musculoskeletal Tumor Society (MSTS) score was 99.5%. According to our results, locking plate and fibular strut graft in Dormans classification types IB and IIB results in a favorable outcome in managing UBC of the proximal femur in the paediatric population.

Skin Mast Cell Promotion in Random Skin Flaps in Rats using Bone Marrow Mesenchymal Stem Cells and Amniotic Membrane

PubMed

Chehelcheraghi, Farzaneh; Abbaszadeh, Abolfazl; Tavafi, Magid

2018-03-06

Skin flap procedures are employed in plastic surgery, but failure can lead to necrosis of the flap. Studies have used bone marrow mesenchymal stem cells (BM-MSCs) to improve flap viability. BM-MSCs and acellular amniotic membrane (AAM) have been introduced as alternatives. The objective of this study was to evaluate the effect of BM-MSCs and AAM on mast cells of random skin flaps (RSF) in rats. RSFs (80 × 30 mm) were created on 40 rats that were randomly assigned to one of four groups, including (I) AAM, (II) BM-MSCs, (III) BM-MSCs/AAM, and (IV) saline (control). Transplantation was carried out during the procedure (zero day). Flap necrosis was observed on day 7, and skin samples were collected from the transition line of the flap to evaluate the total number and types of mast cells. The development and the total number of mast cells were related to the development of capillaries. The results of one-way ANOVA indicated that there was no statistically significant difference between the mean numbers of mast cell types for different study groups. However, the difference between the total number of mast cells in the study groups was statistically significant (p = 0.001). The present study suggests that the use of AAM/BM-MSCs can improve the total number of mast cells and accelerate the growth of capillaries at the transient site in RSFs in rats.

Does a cemented cage improve revision THA for severe acetabular defects?

PubMed

Hansen, Erik; Shearer, David; Ries, Michael D

2011-02-01

Evidence suggests a growing incidence of revision total hip arthroplasty (THA) including a subset with large acetabular defects. Revision THA for severe acetabular bone loss is associated with a relatively high rate of mechanical failure. We questioned whether cementing a cage to the reconstructed acetabular defect and pelvis would improve the rate of mechanical failure for patients with Type 3 defects (Paprosky et al.) with and without pelvic discontinuity in comparison to historical controls. We retrospectively collected data on 33 patients who underwent 35 revision THAs using an acetabular reconstruction cage cemented to morselized allograft and either structural allograft or trabecular metal augmentation for Type 3 defects in the presence (n = 13) and absence (n = 22) of pelvic discontinuity at a mean followup of 59 months (range, 24-92 months). The primary outcome was mechanical failure, defined as revision of the acetabular reconstruction for aseptic loosening. Revision surgery for mechanical failure occurred in four of the 13 patients with pelvic discontinuity and two of the 22 patients without discontinuity. Radiographic loosening occurred in one patient with and one patient without pelvic discontinuity. Seven of the 35 revisions were subsequently revised for deep infection all in patients who were immunocompromised. Cementing the cage to the pelvis can offer an advantage for treating severe acetabular defects. Trabecular metal augmentation appears to provide better initial mechanical stability than a structural allograft, but successful allograft reconstruction may restore bone stock. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Essential core of the Hawking–Ellis types

NASA Astrophysics Data System (ADS)

Martín-Moruno, Prado; Visser, Matt

2018-06-01

The Hawking–Ellis (Segre–Plebański) classification of possible stress–energy tensors is an essential tool in analyzing the implications of the Einstein field equations in a more-or-less model-independent manner. In the current article the basic idea is to simplify the Hawking–Ellis type I, II, III, and IV classification by isolating the ‘essential core’ of the type II, type III, and type IV stress–energy tensors; this being done by subtracting (special cases of) type I to simplify the (Lorentz invariant) eigenvalue structure as much as possible without disturbing the eigenvector structure. We will denote these ‘simplified cores’ type II0, type III0, and type IV0. These ‘simplified cores’ have very nice and simple algebraic properties. Furthermore, types I and II0 have very simple classical interpretations, while type IV0 is known to arise semi-classically (in renormalized expectation values of standard stress–energy tensors). In contrast type III0 stands out in that it has neither a simple classical interpretation, nor even a simple semi-classical interpretation. We will also consider the robustness of this classification considering the stability of the different Hawking–Ellis types under perturbations. We argue that types II and III are definitively unstable, whereas types I and IV are stable.

Clastogenic and toxicological assessment of cashew (Anacardium occidentale) nut bark extracts in Wistar rats.

PubMed

Owumi, Solomon E; Fatoki, John O; Gbadegesin, Michael A; Odunola, Oyeronke A

2015-01-01

Occupational exposures to environmental toxicants have been associated with the onset of skin lesions-including cancers. Identification and reduction of exposure to such compounds is an important public health goal. We examined the effect of cashew shell oil (CSO), used in skin tattooing for its potential to induce skin transformation in rats. Corn oil and CSO (25, 50, and 100%) were topically applied to depilated sections of Wistar' rat skin (groups: I-IV) for six weeks. Effect of treatments on serum transaminases activity, histological changes in hepatocytes and induction of micronuclei in the bone marrow were examined. In addition, CSO-induced hepatocyte proliferation was also quantified. All animals survived the course of the study. Reduced percentage change in body weight and physical trauma were observed in CSO-treated rat. The effects were more prominent in Group IV (100% CSO). Relative liver weights and number of hepatocytes (cells/mm(2)) increased significantly in groups II-IV relative to control (p < 0.05). Serum transaminases activities were not significantly (p > 0.05) affected in treated groups. Hepatic histopathology revealed moderate sinusoidal congestion (group II), in addition to portal congestion in (group III), with mononuclear cellular infiltration (group IV) animals. In addition, CSO induced significant micronuclei formation of polychromatic erythrocyte (mPCEs) in the rat bone marrow (p < 0.05) when compared with control. Topical application of CSO disrupted skin cells integrity resulting in physical trauma. In addition, CSO appears to be clastogenic and induces hepatocyte proliferation. Occupational exposure to CSO especially for engraving tattoos in humans should be discouraged and further studies need to be conducted.

PET/CT study performed after an oral administration of 18F-fluoride.

PubMed

Zacchi, Samara Riguete; Valadares, Agnes Araújo; Duarte, Paulo Schiavom; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2013-12-01

A 52-year-old woman with right breast cancer was referred for 18F-fluoride whole-body PET/CT for the assessment of bone metastases. The peripheral i.v. access was not obtained after multiple attempts. The radiopharmaceutical was administered by oral route.

Bisphosphonate-related osteonecrosis of the jaw: historical, ethical, and legal issues associated with prescribing.

PubMed

Faiman, Beth; Pillai, Aiswarya Lekshmi Pillai Chandran; Benghiac, Ana Gabriela

2013-01-01

The long-term effects of many drugs are unknown. Established risks are communicated to patients who participate in clinical trials during the informed consent process. However, unknown and unanticipated side effects of medications may occur years after treatment. Patients with metastatic bone cancer experience an imbalance between tumor cells and the bone marrow microenvironment. Increased cytokine release, osteoclastic activity, and uncoupled osteoblastic activity lead to weakened bone structure and osteolytic lesions. The bisphosphonates are a class of drugs available in IV and oral formulations to treat and prevent bone loss and decrease the risk of skeletal-related events. Intravenous bisphosphonates such as zoledronic acid and pamidronate disodium are approved by the US Food and Drug Administration for the treatment of bone pain and hypercalcemia of malignancy and the prevention of painful bone fractures in patients with metastatic bone cancer. Oral bisphosphonates such as alendronate, risedronate, and etidronate are used to reduce the risk of skeletal fractures in patients with osteoporosis and in breast cancer. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but painful complication of treatment characterized by infection, exposed bone, and poor wound healing. In this article, we discuss BRONJ and identify past, present, and future ethical and legal issues surrounding bisphosphonate administration.

[Case-control study on two suturing methods for the repairing of complete rupture of the deltoid ligament].

PubMed

Zhang, Tao; Wan, Chun-you; Ma, Bao-tong; Xu, Wei-guo; Mei, Xiao-long; Jia, Peng; Liu, Lei

2016-05-01

To compare clinical outcomes between two suturing methods using non absorbable materials through drilling the bone and suturing anchors for the treatment of complete rupture of the deltoid ligament. From January 2009 to January 2013, 58 hospitalized patients with ankle fracture combined with complete rupture of the deltoid ligament were treated with suturing using non absorbable materials through drilling the bone or suturing anchors. There were 29 patients who received suturing treatments using non absorbable materials through drilling the bone (Group A), including 18 males and 11 females, with an average age of (39.76 +/- 11.81) years old. According to the Lauge-Hansen classification, 12 patients had supination external rotation (SER) injuries with IV degree, 5 patients had pronation external rotation (PER) injuries with III degree, 10 patients had PER injuries with IV degrss, and 2 patients had pronation abduction injuries with III degree. There were 29 patients who received treatments with suturing using anchors (Group B), including 14 males and 15 females, with an average age of (41.79 +/- 13.28) years old. According to the Lauge-Hansen classification,9 patients had SER injuries with IV degree, 6 patients had PER injuries with III degree,13 patients had PER injuries with IV degree, and 1 patient had pronation abduction injuries with III degree. All the patients were treated with open reduction and internal fixation, as well as reconstruction of deltoid ligaments to restore the stability of the medial ankle structures. The clinical examination, imaging evaluation, American society for ankle surgery (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to evaluate the clinical results after operation, and the results of the two groups were compared and analyzed statistically. The follow-up duration of the 58 patients ranged from 23 to 40 months,with an average of 27.3 months. All the patients had fracture union, and the mean healing time was 12.3 weeks (ranged, 10 to 17 weeks). There were no incision complications and ankle instability. There were no significant differences between two groups in AOFAS (P=0.666) and the VAS (P=0.905). Treatments of complete rupture of the deltiod ligaments with the two suturing methods get similar good clinical effects, but the suturing using non absorbable materials through drilling the bone has several advantages such as reducing the financial burden of patients, saving social medical resources and avoiding the shortcoming in difficult removal of anchor suture.

Observational properties of decameter type IV bursts

NASA Astrophysics Data System (ADS)

Melnik, Valentin; Brazhenko, Anatoly; Rucker, Helmut; Konovalenko, Alexander; Briand, Carine; Dorovskyy, Vladimir; Zarka, Philippe; Frantzusenko, Anatoly; Panchenko, Michael; Poedts, Stefan; Zaqarashvili, Teimuraz; Shergelashvili, Bidzina

2013-04-01

Oscillations of decameter type IV bursts were registered during observations of solar radio emission by UTR-2, URAN-2 and NDA in 2011-2012. Large majority of these bursts were accompanied by coronal mass ejections (CMEs), which were observed by SOHO and STEREO in the visible light. Only in some cases decameter type IV bursts were not associated with CMEs. The largest periods of oscillations P were some tens of minutes. There were some modes of long periods of oscillations simultaneously. Periods of oscillations in flux and in polarization profiles were close. Detailed properties of oscillations at different frequencies were analyzed on the example of two type IV bursts. One of them was observed on April 7, 2011 when a CME happened. Another one (August 1, 2011) was registered without any CME. The 7 April type IV burst had two periods in the frames 75-85 and 35-85 minutes. Interesting feature of these oscillations is decreasing periods with time. The observed decreasing rates dP/dt equaled 0.03-0.07. Concerning type IV burst observed on August 1, 2011 the period of its oscillations increases from 17 min. at 30 MHz to 44 min. at 10 MHz. Connection of type IV burst oscillations with oscillations of magnetic arches and CMEs at corresponding altitudes are discussed. The work is fulfilled in the frame of FP7 project "SOLSPANET".

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

PubMed Central

Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

A novel explanation of corneal clouding in a bone marrow transplant-treated patient with Hurler syndrome

PubMed Central

Yuan, Ching; Bothun, Erick D.; Hardten, David R.; Tolar, Jakub; McLoon, Linda K.

2016-01-01

One common complication of mucopolysaccharidosis I-Hurler (MPS1-H) is corneal clouding, which occurs despite current treatments, including bone marrow transplantation. Human corneas were obtained from a 14 year old subject with MPS1-H and visual disability from progressive corneal clouding despite a prior bone marrow transplant at age 2. This was compared to a cornea from a 17 year old donated to our eye bank after his accidental death. The corneas were analyzed microscopically after staining with Alcian blue, antibodies to collagen I, IV, VI, and α-smooth muscle actin. Differences in levels of expression of the indicated molecules were assessed. Corneas from Hurler and control mice were examined similarly to determine potential mechanistic overlap. The MPS1-H subject cornea showed elevations in mucopolysaccharide deposition. The MPS1-H and Hurler mice corneas showed increased and disorganized expression of collagen I and IV relative to the control corneas. The MPS1-H corneas also showed increased and disordered expression of collagen VI. Positive expression of α-smooth muscle actin indicated myofibroblast conversion within the MPS1-H cornea in both the patient and mutant mouse material compared to normal human and control mouse cornea. Increased deposition of collagens and smooth muscle actin correlate with corneal clouding, providing a potential mechanism for corneal clouding despite bone marrow transplantation in MPS1-H patients. It might be possible to prevent or slow the onset of corneal clouding by treating the cornea with drugs known to prevent myofibroblast conversion. PMID:27235795

Bone morphology changes around two types of bone-level implants installed in fresh extraction sockets--a histomorphometric study in Beagle dogs.

PubMed

Alharbi, Hend M; Babay, Nadir; Alzoman, Hamad; Basudan, Sumaya; Anil, Sukumaran; Jansen, John A

2015-09-01

Minimizing crestal bone loss following immediate implant placement is considered the most challenging aspect in implant therapy. Implant surface topography and chemical modifications have been shown to influence the success of Osseointegration. The Straumann Bone Level implant, featuring SLActive surface, has been introduced with the aim of enhancing bone apposition. Similarly, the OsseoSpeed implants from Astra Tech claim to have an enhanced osseointegration. Because of the specific features in the implant design, both companies claim that crestal resorption is minimal with these implants. To evaluate the osseointegration and crestal bone level following immediate placement of Straumann Bone Level implant and OsseoSpeed implants in fresh extraction sockets in Beagle dogs. The distal roots of the second, third and fourth premolars were extracted in both sides of the mandible. The distal roots were removed using a dental elevator. A total of 60 fixtures were installed in 10 Beagle dogs. Two types of implants were used: Straumann Bone-Level implants, which were 8 × 3.3 mm in size, and Astra Tech OsseoSpeed 3.5 S MicroThread implants, which were 8 × 3.5 mm in size. The histomorphometrical evaluation was performed at the end of 4- and 12-week healing. The implant-bone contact and bone volume percentage were assessed. The bone-to-implant contact (BIC) and the bone volume did not show any significant changes for both types of implants. The OsseoSpeed™ implants showed 67.4% and 65.3% BIC, respectively, at 4 and 12 weeks compared with 71.7 and 73.1 for the Straumann Bone-Level implants. The bone volume around both types of implants did not differ significantly at both time periods. The crestal bone resorption was observed for both types of implants. The first BIC at buccal side and lingual side of the implants also did not differ significantly for both implant systems. This study showed that Straumann Bone Level and OsseoSpeed implants induced similar bone response after immediate implantation at 4 and 12 weeks. The immediate implant placement resulted in peri-implant crestal bone-level changes for both types of implants. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Endovascular repair of an iliac artery aneurysm in a patient with Ehlers-Danlos syndrome type IV.

PubMed

Tonnessen, Britt H; Sternbergh, W Charles; Mannava, Krishna; Money, Samuel R

2007-01-01

Ehlers-Danlos type IV (EDS-IV) is an inherited condition most notable for its associated vascular complications. Patients are prone to aneurysm formation, arterial dissection, and spontaneous vessel rupture. Intervention for the vascular pathology of EDS-IV carries high morbidity and mortality. We describe a case of a 57-year-old man with EDS-IV and an expanding iliac aneurysm who underwent successful endovascular repair with a stent-graft. Endovascular aneurysm repair is feasible and should be considered for patients with EDS-IV.

Photodynamic therapy of diseased bone

NASA Astrophysics Data System (ADS)

Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

2005-08-01

Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support the application of PDT to the treatment of primary or metastatic lesions within bone. Secondly, that ALA-PDT may be useful as a treatment for osteomyelitis. Further studies aim to optimize the parameters of delivering PDT into bone and explore imaging technologies that can be used for clinical PDT.

Is Bone Grafting Necessary in the Treatment of Malunited Distal Radius Fractures?

PubMed Central

Disseldorp, Dominique J. G.; Poeze, Martijn; Hannemann, Pascal F. W.; Brink, Peter R. G.

2015-01-01

Background Open wedge osteotomy with bone grafting and plate fixation is the standard procedure for the correction of malunited distal radius fractures. Bone grafts are used to increase structural stability and to enhance new bone formation. However, bone grafts are also associated with donor site morbidity, delayed union at bone–graft interfaces, size mismatch between graft and osteotomy defect, and additional operation time. Purpose The goal of this study was to assess bone healing and secondary fracture displacement in the treatment of malunited distal radius fractures without the use of bone grafting. Methods Between January 1993 and December 2013, 132 corrective osteotomies and plate fixations without bone grafting were performed for malunited distal radius fractures. The minimum follow-up time was 12 months. Primary study outcomes were time to complete bone healing and secondary fracture displacement. Preoperative and postoperative radiographs during follow-up were compared with each other, as well as with radiographs of the uninjured side. Results All 132 osteotomies healed. In two cases (1.5%), healing took more than 4 months, but reinterventions were not necessary. No cases of secondary fracture displacement or hardware failure were observed. Significant improvements in all radiographic parameters were shown after corrective osteotomy and plate fixation. Conclusion This study shows that bone grafts are not required for bone healing and prevention of secondary fracture displacement after corrective osteotomy and plate fixation of malunited distal radius fractures. Level of evidence Therapeutic, level IV, case series with no comparison group PMID:26261748

Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

PubMed Central

Richardson, Richard B

2011-01-01

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. PMID:21204614

Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

PubMed

Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c <5.7% and fasting glucose >110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of rat serum alkaline phosphatase isoenzyme by means of wheat germ agglutinin.

PubMed

Wada, H; Niwa, N; Hayakawa, T; Tsuge, H

1997-01-01

Wheat germ agglutinin (WGA) precipitates bone type serum alkaline phosphatase (sALP) isoenzyme specifically. The precipitates are composed of the macromolecules of WGA and "bone type sALP" (WGA-ALP complex). In order to use bone type sALP as a marker in polyacrylamide gel electrophoresis (PAGE), a method to separate "bone type sALP" from the "WGA-ALP complex" was established by using N-acetyl-D-glucosamine (GlcNAc)-Sepharose 6E column chromatography. It was concluded that this method is useful for clinical examination in the rat.

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone

PubMed Central

Pritchard, J.M.; Papaioannou, A.; Tomowich, C.; Giangregorio, L.M.; Atkinson, S.A.; Beattie, K.A.; Adachi, J.D.; DeBeer, J.; Winemaker, M.; Avram, V.; Schwarcz, H.P.

2016-01-01

Purpose The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. Methods Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 μm2) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student’s t-test for normally distributed data and Mann–Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. Results Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5] years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4] years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98] wt.% Ca versus 19.40 [1.07] wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99–4.12] wt.% Ca versus 3.95 [0.71] wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97] wt.% Ca for type 2 diabetes versus 20.44 [1.30] wt.% Ca for controls, p=0.121). Conclusion The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes. PMID:23356988

A comparative study of percutaneous atherectomy for femoropopliteal arterial occlusive disease.

PubMed

Gu, Yongquan; Malas, Mahmoud B; Qi, Lixing; Guo, Lianrui; Guo, Jianming; Yu, Hengxi; Tong, Zhu; Gao, Xixiang; Zhang, Jian; Wang, Zhonggao

2017-08-01

SilverHawk™ directional atherectomy has been used to treat more than 300 thousand cases of lower extremity atherosclerotic occlusive disease in the world since it was approved by FDA in 2003. This study aimed to analyze the safety and effectiveness of symptomatic femoral popliteal atherosclerotic disease treated by directional atherectomy (DA). Clinical data of all consecutive patients treated with percutaneous atherectomy utilizing the SilverHawk™ plaque excision was retrospectively analyzed. The anatomic criteria of the atherosclerotic lesions were divided into four types: type I stenosis; type II occlusion; type III in-stent restenosis; type IV stent occlusion. There were 160 patients treated during the study period. Intermittent claudication in 75 patients (47%), rest pain in 55 patients (34.5%) and tissue loss in 30 patients (18.5%). The number of patients was 72, 15, 49 and 24 in type I, II, III and IV lesions, respectively. Technical success rate was 98.6%, 93.3%, 97.9% and 91.7% in type I, II, III and IV lesions, respectively. Debris of intimal plaque was captured by protection device in 92 patients (71.3%). The mean follow-up period was 23.5±10.4 months. Restenosis rate of type I to IV lesions was 21%, 36%, 36% and 40% respectively. Restenosis rate in type I lesion was significantly lower than that in type III and IV lesions (P<0.05). Patients with tissue loss responded to revascularization as follow: type I, 11/13 healed or reduced (84.6%), type II, 3/3 patients improved (100%), type III, 5/6 patients improved (83.3%) and type IV 4/4 healed (100%). In type IV group, four patients had in-stent thrombosis found by postoperative Duplex ultrasonography. They all underwent DA after catheter-directed thrombolysis with good angiographic results. Percutaneous DA is safe and effective for both de-novo atherosclerotic and in-stent stenotic or occlusive lesions. Thrombolysis before plaque excision is recommended in case of in-stenting thrombosis.

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

PubMed Central

Vora, Kalpit A; Porter, Gene; Peng, Roche; Cui, Yan; Pryor, Kellyann; Eiermann, George; Zaller, Dennis M

2009-01-01

Background Current literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo. Results The DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen. Conclusion These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge. PMID:19358731

Collagen Scaffolds in Bone Sialoprotein-Mediated Bone Regeneration

PubMed Central

Kruger, Thomas E.; Miller, Andrew H.; Wang, Jinxi

2013-01-01

Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds αvβ 3 and αvβ 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration. PMID:23653530

Collagen scaffolds in bone sialoprotein-mediated bone regeneration.

PubMed

Kruger, Thomas E; Miller, Andrew H; Wang, Jinxi

2013-01-01

Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds α v β 3 and α v β 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration.

Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.

PubMed

Mishina, Yuji; Starbuck, Michael W; Gentile, Michael A; Fukuda, Tomokazu; Kasparcova, Viera; Seedor, J Gregory; Hanks, Mark C; Amling, Michael; Pinero, Gerald J; Harada, Shun-ichi; Behringer, Richard R

2004-06-25

Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling.

The concentration of manganese, iron and strontium in bone of red fox Vulpes vulpes (L. 1758).

PubMed

Budis, Halina; Kalisinska, Elzbieta; Lanocha, Natalia; Kosik-Bogacka, Danuta I

2013-12-01

The aims of the study were to determine manganese (Mn), iron (Fe) and strontium (Sr) concentrations in fox bone samples from north-western Poland and to examine the relationships between the bone Mn, Fe and Sr concentrations and the sex and age of the foxes. In the studied samples of fox cartilage, cartilage with adjacent compact bone, compact bone and spongy bone, the concentrations of the analysed metals had the following descending order: Fe > Sr > Mn. The only exception was in compact bone, in which the concentrations were arranged in the order Sr > Fe > Mn. Manganese concentrations were significantly higher in cartilage, compact bone and cartilage with compact bone than in spongy bone. Iron concentrations were higher in cartilage and spongy bone compared with compact bone. Strontium concentrations were greater in compact bone than in cartilage and spongy bone. The manganese, iron and strontium concentrations in the same type of bone material in many cases correlated with each other, with the strongest correlation (r > 0.70) between Mn and Fe in almost all types of samples. In addition, concentrations of the same metals in different bone materials were closely correlated for Mn and Fe in cartilage and cartilage with adjacent compact bone, and for Sr in compact bone and cartilage with compact bone. In the fox from NW Poland, there were no statistically significant differences in Mn, Fe and Sr in any of the types of bone material between the sexes and immature and adult foxes.

Injection of Unicameral Bone Cysts with Bone Marrow Aspirate and Demineralized Bone Matrix Avoids Open Curettage and Bone Grafting in a Retrospective Cohort

PubMed Central

Gundle, Kenneth R.; Bhatt, Etasha M.; Punt, Stephanie E.; Bompadre, Viviana; Conrad, Ernest U.

2017-01-01

Background: Many treatment options exist for unicameral bone cysts (UBC), without clear evidence of superiority. Meta-analyses have been limited by small numbers of patients in specific anatomic and treatment subgroups. The purpose of this study was to report the outcomes of injecting bone marrow aspirate and demineralized bone matrix (BMA/DBM) for the treatment of proximal humerus UBC. Methods: Fifty-one patients with proximal humerus lesions treated by BMA/DBM injection were retrospectively reviewed from a single academic medical center. Results: The mean number of injections performed per patient was 2.14 (range 1-5). Eleven patients underwent only one injection (22%), an additional 19 patients completed treatment after two injections (37%), four patients healed after three injections (8%), and one patient healed after four injections (2%). The cumulative success rate of serial BMA/DBM injections was 22% (11/51), 58% (30/51), 67% (34/51), and 69% (35/51). Eleven patients (22%) ultimately underwent open curettage and bone grafting, and five patients (10%) were treated with injection of calcium phosphate bone substitute. Conclusion: A BMA/DBM injection strategy avoided an open procedure in 78% of patients with a proximal humerus UBC. The majority of patients underwent at least 2 injection treatments. Level of Evidence: Level IV retrospective cohort study. PMID:28694887

Treatment based on the type of infected TKA improves infection control.

PubMed

Kim, Young-Hoo; Choi, Yoowang; Kim, Jun-Shik

2011-04-01

A classification system with four types of infected TKAs has been commonly used to determine treatment, especially with regard to whether the prosthesis should be removed or retained. We asked whether (1) the classification-dictated treatment of the four types of infection after TKA would control infection and maintain functional TKA; (2) repeated débridement and two-stage TKA would further improve the infection control rate after initial treatment; and (3) fixation of TKA prosthesis to the host bone was achieved. We retrospectively reviewed 114 patients with 116 infected TKAs. We determined the infection control rate after initial treatment, repeated débridement and two-stage TKA. We evaluated the functional and radiographic results using the Knee Society and Hospital for Special Surgery knee scoring systems. The minimum followup was 2 years (mean, 5.6 years; range, 2-8 years). The overall infection control rate was 100% in all patients. All patients with early superficial postoperative infection, 94% of patients with early deep postoperative infection, 96% of patients with late chronic infection, and 86% of patients with acute hematogenous infection maintained functioning knee prosthesis at the final followup. One hundred nine of the 114 patients could walk with no or only slight pain and maintained functioning knee prostheses. These 109 patients had stable fixation of the TKA prosthesis to host bone. The techniques proposed by the classification effectively controlled infection and maintained functional TKA with firm fixation of the TKA prosthesis in most patients. Repeated débridement and two-stage TKA further improved the control of infection and functional TKA after initial treatment. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Evaluation of Vertical Bone Regeneration Using Block and Particulate Forms of Bio-Oss Bone Graft: A Histologic Study in the Rabbit Mandible.

PubMed

Veis, Alexander; Dabarakis, Nikolaos; Koutrogiannis, Christos; Barlas, Irodis; Petsa, Elina; Romanos, Georgios

2015-06-01

The aim of the present study was to evaluate histologically vertical bone regeneration outcomes after using bovine bone graft material in block and granular forms. The buccal bony plates of the outer mandibles of 10 New Zealand rabbits received Bio-Oss blocks that were immobilized using orthopedic mini-plates, and another 10 received granular forms that were gently packed and stabilized into the custom-made perforated metallic cubes. The mean graft area (GA), new bone area (NBA), bone-to-graft contact (BGC), and maximum vertical height reached by the new bone development (MVH) were histometrically evaluated and showed no significant differences between 2 graft types. The new bone was observed mostly close to the basal bone and developed penetrating the trabecular scaffold in the form of seams that covered the intralumen surfaces of the block type graft, while in the granular graft type the new bone was observed to grow between the graft particles usually interconnecting them. Either form of Bio-Oss was capable of providing considerable vertical bone augmentation.

Secretion of TcpF by the Vibrio cholerae Toxin-Coregulated Pilus Biogenesis Apparatus Requires an N-Terminal Determinant

PubMed Central

Megli, Christina J.

2013-01-01

Type IV pili are important for microcolony formation, biofilm formation, twitching motility, and attachment. We and others have shown that type IV pili are important for protein secretion across the outer membrane, similar to type II secretion systems. This study explored the relationship between protein secretion and pilus formation in Vibrio cholerae. The toxin-coregulated pilus (TCP), a type IV pilus required for V. cholerae pathogenesis, is necessary for the secretion of the colonization factor TcpF (T. J. Kirn, N. Bose, and R. K. Taylor, Mol. Microbiol. 49:81–92, 2003). This phenomenon is not unique to V. cholerae; secreted virulence factors that are dependent on the presence of components of the type IV pilus biogenesis apparatus for secretion have been reported with Dichelobacter nodosus (R. M. Kennan, O. P. Dhungyel, R. J. Whittington, J. R. Egerton, and J. I. Rood, J. Bacteriol. 183:4451–4458, 2001) and Francisella tularensis (A. J. Hager et al., Mol. Microbiol. 62:227–237, 2006). Using site-directed mutagenesis, we demonstrated that the secretion of TcpF is dependent on the presence of selected amino acid R groups at position five. We were unable to find other secretion determinants, suggesting that Y5 is the major secretion determinant within TcpF. We also report that proteins secreted in a type IV pilus biogenesis apparatus-dependent manner have a YXS motif within the first 15 amino acids following the Sec cleavage site. The YXS motif is not present in proteins secreted by type II secretion systems, indicating that this is unique to type IV pilus-mediated secretion. Moreover, we show that TcpF interacts with the pilin TcpA, suggesting that these proteins are secreted by the type IV pilus biogenesis system. These data provide a starting point for understanding how type IV pili can mediate secretion of virulence factors important for bacterial pathogenesis. PMID:23564177

Assessing a relationship between bone microstructure and growth rate: a fluorescent labelling study in the king penguin chick (Aptenodytes patagonicus).

PubMed

de Margerie, E; Robin, J-P; Verrier, D; Cubo, J; Groscolas, R; Castanet, J

2004-02-01

Microstructure-function relationships remain poorly understood in primary bone tissues. The relationship between bone growth rate and bone tissue type, although documented in some species by previous works, remains somewhat unclear and controversial. We assessed this relationship in a species with extreme adaptations, the king penguin (Aptenodytes patagonicus). These birds have a peculiar growth, interrupted 3 months after hatching by the austral winter. Before this interruption, chicks undergo extremely rapid statural and ponderal growth. We recorded experimentally (by means of fluorescent labelling) the growth rate of bone tissue in four long bones (humerus, radius, femur and tibiotarsus) of four king penguin chicks during their fastest phase of growth (3-5 weeks after hatching) and identified the associated bone tissue types ('laminar', 'longitudinal', 'reticular' or 'radial' fibro-lamellar bone tissue). We found the highest bone tissue growth rate known to date, up to 171 microm day(-1) (mean 55 microm day(-1)). There was a highly significant relationship between bone tissue type and growth rate (P<10(-6)). Highest rates were obtained with the radial microarchitecture of fibro-lamellar bone, where cavities in the woven network are aligned radially. This result supports the heuristic value of a relationship between growth rate and bone primary microstructure. However, we also found that growth rates of bone tissue types vary according to the long bone considered (P<10(-5)) (e.g. growth rates were 38% lower in the radius than in the other long bones), a result that puts some restriction on the applicability of absolute growth rate values (e.g. to fossil species). The biomechanical disadvantages of accelerated bone growth are discussed in relation to the locomotor behaviour of the chicks during their first month of life.

Classification of non-union.

PubMed

Megas, Panagiotis; Panagiotis, Megas

2005-11-01

A substantial number of experimental and clinical studies have established that the cornerstones for successful bone-healing are biomechanical stability and biological vitality of the bone, as they both provide an environment in which new bone can be formed. Non-union of long bones is a significant consequence in treating fractures. Many approaches to prevent fracture non-union have been proposed. Depending on the type and location of the non-union, treatment options include various types of bone fixation, with or without supplemental bone graft or other biophysical enhancements.

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa.

PubMed

Persat, Alexandre; Inclan, Yuki F; Engel, Joanne N; Stone, Howard A; Gitai, Zemer

2015-06-16

Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity.

Treatment of type II and type III open tibia fractures in children.

PubMed

Bartlett, C S; Weiner, L S; Yang, E C

1997-07-01

To determine whether severe open tibial fractures in children behave like similar fractures in adults. A combined retrospective and prospective review evaluated treatment protocol for type II and type III open tibial fractures in children over a ten-year period from 1984 to 1993. Twenty-three fractures were studied in children aged 3.5 to 14.5 (18 boys and 5 girls). There were six type II, eight type IIIA, and nine type IIIB fractures. Type I fractures were not included. Seven fractures were comminuted with significant butterfly fragments or segmental patterns. Treatment consisted of adequate debridement of soft tissues, closure of dead space, and stabilization with external fixation. Bone debridement only included contaminated devitalized bone or devitalized bone without soft tissue coverage. Bone that could be covered despite periosteal stripping was preserved. Clinical and roentgenographic examinations were used to determine time to union. All fractures in this series healed between eight and twenty-six weeks. Wound coverage included two flaps, three skin grafts, and two delayed primary closures. No bone grafts were required. There were no deep infections, growth arrests, or malunions. Follow-up has ranged from six months to four years. Open tibia fractures in children differ from similar fractures in adults in the following ways: soft tissues have excellent healing capacity, devitalized bone that is not contaminated or exposed can be saved and will become incorporated, and external fixation can be maintained until the fracture has healed. Periosteum in young children can form bone even in the face of bone loss.

Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.;

Rare Autosomal Recessive Cardiac Valvular Form of Ehlers-Danlos Syndrome Results from Mutations in the COL1A2 Gene That Activate the Nonsense-Mediated RNA Decay Pathway

PubMed Central

Schwarze, Ulrike; Hata, Ryu-Ichiro; McKusick, Victor A.; Shinkai, Hiroshi; Hoyme, H. Eugene; Pyeritz, Reed E.; Byers, Peter H.

2004-01-01

Splice site mutations in the COL1A2 gene of type I collagen can give rise to forms of Ehlers-Danlos syndrome (EDS) because of partial or complete skipping of exon 6, as well as to mild, moderate, or lethal forms of osteogenesis imperfecta as a consequence of skipping of other exons. We identified three unrelated individuals with a rare recessively inherited form of EDS (characterized by joint hypermobility, skin hyperextensibility, and cardiac valvular defects); in two of them, COL1A2 messenger RNA (mRNA) instability results from compound heterozygosity for splice site mutations in the COL1A2 gene, and, in the third, it results from homozygosity for a nonsense codon. The splice site mutations led to use of cryptic splice donor sites, creation of a downstream premature termination codon, and extremely unstable mRNA. In the wild-type allele, the two introns (IVS11 and IVS24) in which these mutations occurred were usually spliced slowly in relation to their respective immediate upstream introns. In the mutant alleles, the upstream intron was removed, so that exon skipping could not occur. In the context of the mutation in IVS24, computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site. These findings suggest that the order of intron removal is an important variable in prediction of mutation outcome at splice sites and that folding of the nascent mRNA could be one element that contributes to determination of order of splicing. The complete absence of proα2(I) chains has the surprising effect of producing cardiac valvular disease without bone involvement. PMID:15077201

Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway.

PubMed

Schwarze, Ulrike; Hata, Ryu-Ichiro; McKusick, Victor A; Shinkai, Hiroshi; Hoyme, H Eugene; Pyeritz, Reed E; Byers, Peter H

2004-05-01

Splice site mutations in the COL1A2 gene of type I collagen can give rise to forms of Ehlers-Danlos syndrome (EDS) because of partial or complete skipping of exon 6, as well as to mild, moderate, or lethal forms of osteogenesis imperfecta as a consequence of skipping of other exons. We identified three unrelated individuals with a rare recessively inherited form of EDS (characterized by joint hypermobility, skin hyperextensibility, and cardiac valvular defects); in two of them, COL1A2 messenger RNA (mRNA) instability results from compound heterozygosity for splice site mutations in the COL1A2 gene, and, in the third, it results from homozygosity for a nonsense codon. The splice site mutations led to use of cryptic splice donor sites, creation of a downstream premature termination codon, and extremely unstable mRNA. In the wild-type allele, the two introns (IVS11 and IVS24) in which these mutations occurred were usually spliced slowly in relation to their respective immediate upstream introns. In the mutant alleles, the upstream intron was removed, so that exon skipping could not occur. In the context of the mutation in IVS24, computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site. These findings suggest that the order of intron removal is an important variable in prediction of mutation outcome at splice sites and that folding of the nascent mRNA could be one element that contributes to determination of order of splicing. The complete absence of pro alpha 2(I) chains has the surprising effect of producing cardiac valvular disease without bone involvement.

The effect of carrier type on bone regeneration of demineralized bone matrix in vivo.

PubMed

Tavakol, Shima; Khoshzaban, Ahad; Azami, Mahmoud; Kashani, Iraj Ragerdi; Tavakol, Hani; Yazdanifar, Mahbube; Sorkhabadi, Seyed Mahdi Rezayat

2013-11-01

Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone-repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC.

Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

PubMed Central

Starup-Linde, Jakob

2012-01-01

Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone markers and the similarities and differences of type 1- and type 2-diabetics regarding bone markers will be evaluated. A systematic literature search was conducted using PubMed, Embase, Cinahl, and SveMed+ with the search terms: “Diabetes mellitus,” “Diabetes mellitus type 1,” “Insulin dependent diabetes mellitus,” “Diabetes mellitus type 2,” “Non-insulin dependent diabetes mellitus,” “Bone,” “Bone and Bones,” “Bone diseases,” “Bone turnover,” “Hemoglobin A Glycosylated,” and “HbA1C.” After removing duplicates from this search 1,188 records were screened by title and abstract and 75 records were assessed by full text for inclusion in the review. In the end 43 records were chosen. Bone formation and resorption markers are investigated as well as bone regulating systems. T1D is found to have lower osteocalcin and CTX, while osteocalcin and tartrate-resistant acid are found to be lower in T2D, and sclerostin is increased and collagen turnover markers altered. Other bone turnover markers do not seem to be altered in T1D or T2D. A major problem is the lack of histomorphometric studies in humans linking changes in turnover markers to actual changes in bone turnover and further research is needed to strengthen this link. PMID:23482417

Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin.

PubMed

Sethuraman, G; Sreenivas, V; Yenamandra, V K; Gupta, N; Sharma, V K; Marwaha, R K; Bhari, N; Irshad, M; Kabra, M; Thulkar, S

2015-01-01

Patients with congenital ichthyosis, especially those with darker skin types, are at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone health have not been studied previously, in ichthyosis. To determine the threshold levels of 25(OH)D and PTH for impaired bone health in children with congenital ichthyosis. In this cross-sectional study, 119 children with ichthyosis and 168 controls were recruited. Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase (ALP) were measured. Radiological screening for rickets was carried out only in children with ichthyosis. Forty-seven children with ichthyosis had either clinical or radiological evidence of rickets. The correlation between serum 25(OH)D and PTH showed that a serum level of 25(OH)D 8 ng mL(-1) was associated with a significant increase in PTH. The correlation between PTH and ALP showed that a serum PTH level of 75 pg mL(-1) was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were found to have significantly increased PTH, ALP and radiological rickets scores compared with common ichthyosis. Serum levels of 25(OH)D ≤ 8 ng mL(-1) and PTH ≥ 75 pg mL(-1) significantly increases the risk for development of rickets [odds ratio (OR) 2·8; 95% confidence interval (CI) 1·05-7·40; P = 0·04] in ichthyosis. Among the different types, patients with ARCI (OR 4·83; 95% CI 1·74-13·45; P < 0·01) and EI (OR 5·71; 95% CI 1·74-18·79; P < 0·01) are at an increased risk of developing rickets. © 2014 British Association of Dermatologists.

Functional classification of mitochondrion-rich cells in euryhaline Mozambique tilapia (Oreochromis mossambicus) embryos, by means of triple immunofluorescence staining for Na+/K+-ATPase, Na +/K+/2Cl- cotransporter and CFTR anion channel

USGS Publications Warehouse

Hiroi, J.; McCormick, S.D.; Ohtani-Kaneko, R.; Kaneko, T.

2005-01-01

Mozambique tilapia Oreochromis mossambicus embryos were transferred from freshwater to seawater and vice versa, and short-term changes in the localization of three major ion transport proteins, Na+/K +-ATPase, Na+/K+/2Cl- cotransporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CFTR) were examined within mitochondrion-rich cells (MRCs) in the embryonic yolk-sac membrane. Triple-color immunofluorescence staining allowed us to classify MRCs into four types: type I, showing only basolateral Na+/K +-ATPase staining; type II, basolateral Na+/K +-ATPase and apical NKCC; type III, basolateral Na+/K +-ATPase and basolateral NKCC; type IV, basolateral Na +/K+-ATPase, basolateral NKCC and apical CFTR. In freshwater, type-I, type-II and type-III cells were observed. Following transfer from freshwater to seawater, type-IV cells appeared at 12 h and showed a remarkable increase in number between 24 h and 48 h, whereas type-III cells disappeared. When transferred from seawater back to freshwater, type-IV cells decreased and disappeared at 48 h, type-III cells increased, and type-II cells, which were not found in seawater, appeared at 12 h and increased in number thereafter. Type-I cells existed consistently irrespective of salinity changes. These results suggest that type I is an immature MRC, type II is a freshwater-type ion absorptive cell, type III is a dormant type-IV cell and/or an ion absorptive cell (with a different mechanism from type II), and type IV is a seawater-type ion secretory cell. The intracellular localization of the three ion transport proteins in type-IV cells is completely consistent with a widely accepted model for ion secretion by MRCs. A new model for ion absorption is proposed based on type-II cells possessing apical NKCC.

Modulation of type I immediate and type IV delayed immunoreactivity using direct suggestion and guided imagery during hypnosis.

PubMed

Zachariae, R; Bjerring, P; Arendt-Nielsen, L

1989-11-01

Cutaneous reactivity against histamine skin prick test (Type I) and purified tuberculin protein derivative (Mantoux reaction, Type IV) was studied in eight volunteers under hypnosis. Types I and IV immunoreactivity were modulated by direct suggestion (Type I) and guided imagery (Type IV). The volunteers were highly susceptible subjects, selected by means of the Harvard Group Scale of Hypnotic Susceptibility, Form A. When the volunteers underwent hypnotic suggestion to decrease the cutaneous reaction to histamine prick test, a significant (P less than 0.02) reduction of the flare reaction (area of erythema) was observed compared with control histamine skin prick tests. The wheal reaction did not respond to hypnotic suggestion. Neither wheal nor flare reaction could be increased in size by hypnotic suggestion compared with control histamine skin prick tests. A hypnotic suggestion of increasing the Type IV reaction on one arm and decreasing the reaction on the other revealed a significant difference in both erythema size (P less than 0.02) and palpable induration (P less than 0.01). In two cases the reactions were monitored by laser doppler blood flowmetry and skin thickness measurement by ultrasound. The difference between the suggested increased and decreased reaction was 19% for the laser doppler bloodflow (in favor of the augmented side), and 44% for the dermal infiltrate thickness. This study objectively supports the numerous uncontrolled case reports of modulation of immunoreactivity in allergic diseases involving both Type I and Type IV skin reactions following hypnotic suggestions.

Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

PubMed Central

Kadriu, Bashkim; Gold, Philip W; Luckenbaugh, David A; Lener, Marc S; Ballard, Elizabeth D; Niciu, Mark J; Henter, Ioline D; Park, Lawrence T; De Sousa, Rafael Teixeira; Yuan, Peixiong; Machado-Vieira, Rodrigo; Zarate, Carlos A

2017-01-01

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation—the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)—play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 minutes, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness. PMID:28555075

Amplified QCM biosensor for type IV collagenase based on collagenase-cleavage of gold nanoparticles functionalized peptide.

PubMed

Dong, Zong-Mu; Jin, Xin; Zhao, Guang-Chao

2018-05-30

The present study develops a rapid, simple and efficient method for the determination of type IV collagenase by using a specific peptide-modified quartz crystal microbalance (QCM). A small peptide (P1), contains a specific sequence (Pro-Gly) and a terminal cysteine, was synthetized and immobilized to the surface of QCM electrode via the reaction between Au and thiol of the cysteine. The peptide bond between proline and glycine can be specific hydrolyzed cleavage by type IV collagenase, which enabled the modified electrode with a high selectivity toward type IV collagenase. The cleaving process caused a frequency change of QCM to give a signal related to the concentration of type IV collagenase. The morphologies of the modified electrodes were characterized by scanning electron microscope (SEM) and the specific hydrolyzed cleavage process was monitored by QCM. When P1 was modified with gold nanoparticles (P1-Au NPs), the signal could be amplified to further enhance the sensitivity of the designed sensor due to the high-mass of the modified Au NPs. Compared the direct unamplified assay, the values obtained for the limit of detection for type IV collagenase was 0.96 ng mL -1 , yielding about 6.5 times of magnitude improvement in sensitivity. This signal enhanced peptide based QCM biosensor for type IV collagenase also showed good selectivity and sensitivity in complex matrix. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalence of Temporal Bone Fractures in Patients with Mandibular Fractures Using Multidetector-Row CT.

PubMed

Ogura, I; Kaneda, T; Sasaki, Y; Buch, K; Sakai, O

2015-06-01

Temporal bone fracture after mandibular trauma is thought to be rare, and its prevalence has not been reported in the literature. The purpose of this study was to investigate the prevalence of temporal bone fractures in patients with mandibular fractures and the relationship between temporal bone fractures and the mandibular fracture location using multidetector-row computed tomography (MDCT). A prospective study was performed in 201 patients with mandibular fractures who underwent 64-MDCT scans. The mandibular fracture locations were classified as median, paramedian, angle, and condylar types. Statistical analysis for the relationship between prevalence of temporal bone fractures and mandibular fracture locations was performed using χ(2) test with Fisher's exact test. A P-value < 0.05 was considered statistically significant. The percentage of cases with temporal bone fracture was 3.0 % of all patients with mandibular fractures and 19.0 % of those with multiple mandibular fractures of paramedian and condylar type. There was a significant relationship between the incidence of temporal bone fracture and the paramedian- and condylar-type mandibular fracture (P = 0.001). Multiple mandibular fractures of paramedian and condylar type may be a stronger indicator for temporal bone fractures. This study suggests that patients with mandibular fracture, especially the paramedian and condylar type, should be examined for coexisting temporal bone fracture using MDCT.

Osteoporosis, Fractures, and Diabetes

PubMed Central

2014-01-01

It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. PMID:25050121

Bone metastasis from ovarian cancer. Clinical analysis of 26 cases.

PubMed

Zhang, Min; Sun, Jimei

2013-12-01

To study the clinical characteristics of bone metastasis from ovarian cancer, and facilitate physicians to develop treatment strategies. This retrospective study was carried out in the Provincial Hospital Affiliated to Shandong University, Shandong, China. Twenty-six cases of bone metastasis from ovarian cancer treated between January 2002 and May 2008 were reviewed, and the clinical data were collected. In the current study, the incidence of bone metastasis is 0.82%. Twelve cases of bone metastasis occurred in the cervical vertebra, 10 in the lumbar vertebra, 8 in the pelvis, 7 in the thoracic vertebra, 5 in the limbs, one in the ribs, and 2 in the sternum. Lung metastasis occurred concomitantly in 9 cases, liver metastasis in 5 cases, brain metastasis in 4 cases, splenic metastasis in 3 cases, adrenal metastasis in 2 cases, and lymphatic metastasis in 12 cases. Twenty-three cases (88.5%) of bone metastasis were detected in stage III-IV, and 3 (11.5%) in stage II (p=0.000). The survival time in cases treated using comprehensive therapy was longer than those using radiotherapy or chemotherapy alone (p=0.047). Bone metastasis from ovarian cancer is rare, however, the increasing pathological stage of ovarian cancer may add to the risk of bone metastasis, especially in the cases with lung or lymphatic metastasis. The pelvis and vertebral bone are the most common location of bone metastasis, and comprehensive treatment may improve the survival time of patients.

A Comparative Analysis on Two Types of Oral Implants, Bone-Level and Tissue-Level, with Different Cantilever Lengths of Fixed Prosthesis.

PubMed

Mosavar, Alireza; Nili, Monireh; Hashemi, Sayed Raouf; Kadkhodaei, Mahmoud

2017-06-01

Depending on esthetic, anatomical, and functional aspects, in implant-prosthetic restoration of a completely edentulous jaw, the selection of implant type is highly important; however, bone- and tissue-level implants and their stress distribution in bone have not yet been comparatively investigated. Hence, finite element analysis was used to study the influence of cantilever length in a fixed prosthesis on stress distribution in peri-implant bone around these two types of oral implants. A 3D edentulous mandible was modeled. In simulations, a framework with four posterior cantilever lengths and two types of implants, bone-level and tissue-level, was considered. A compressive load was applied to the distal regions of the cantilevers, and the von-Mises stress of peri-implant bone was investigated. The independent t-test and the Pearson correlation coefficient analyzed the results (α = 0.05). Stresses in the cortical bone around the bone-level implants were greater than those in the tissue-level implants with the same cantilever length. In addition, by extending the cantilever length, the stress values in peri-implant bone increased. Therefore, when the cantilever was at its maximum length, the maximum stress was in cortical bone and around the bone-level distal implants. The results of the present study indicate that treatment with tissue-level implants is potentially more advantageous than with bone-level implants for implant-supported fixed prostheses. © 2015 by the American College of Prosthodontists.

Stage IV breast cancer: clinical course and survival of patients with osseous versus extraosseous metastases at initial diagnosis. The GOCS (Grupo Oncológico Cooperativo del Sur) experience.

PubMed

Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Perez, J E; Machiavelli, M; Rodriguez, R; Alvarez, L A

1988-12-01

The medical records of 414 patients with metastatic breast carcinoma treated between 1978 and 1986 were reviewed and 44 women were identified as having stage IV disease when the primary breast lesion was detected. Of these 44 women, 25 had metastatic disease limited to the skeleton while 19 had extraosseous lesions only. The clinical features, response to therapy, and survival were analyzed and compared for both groups. The median survival of those patients with bone-only metastases was 52 months as compared with 13 months for those with extraskeletal lesions (p = 0.0025). The response rate to first-line systemic therapy was similar for both groups (47% for bone metastases and 44% for extraosseous metastases). The median duration of response was 14 months (range, 3-55 months) for patients with bone disease and 8 months (range, 4-43 months) for those with extraskeletal lesions. We conclude that patients with metastatic breast cancer confined to the skeleton at initial diagnosis tend to follow an indolent, chronic course with prolonged survival. Therefore the increase in response rate with aggressive chemotherapy should be balanced against its higher morbidity. Further studies are needed to confirm whether the better prognosis of these patients is determined by the anatomical confinement of the disease to the skeleton or merely reflects the influence of other prognostic factors.

Assessment of bone healing on tibial fractures treated with wire osteosynthesis associated or not with infrared laser light and biphasic ceramic bone graft (HATCP) and guided bone regeneration (GBR): Raman spectroscopy study

NASA Astrophysics Data System (ADS)

Bastos de Carvalho, Fabíola; Aciole, Gilberth Tadeu S.; Aciole, Jouber Mateus S.; Silveira, Landulfo, Jr.; Nunes dos Santos, Jean; Pinheiro, Antônio L. B.

2011-03-01

The aim of this study was to evaluate, through Raman spectroscopy, the repair of complete tibial fracture in rabbits fixed with wire osteosynthesis - WO, treated or not with infrared laser light (λ 780nm, 50mW, CW) associated or not to the use of HATCP and GBR. Surgical fractures were created under general anesthesia (Ketamine 0.4ml/Kg IP and Xilazine 0.2ml/Kg IP), on the tibia of 15 rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with WO. Animals of groups III and V were grafted with hydroxyapatite + GBR technique. Animals of groups IV and V were irradiated at every other day during two weeks (16J/cm2, 4 x 4J/cm2). Observation time was that of 30 days. After animal death the specimens were kept in liquid nitrogen for further analysis by Raman spectroscopy. Raman spectroscopy showed significant differences between groups (p<0.001). It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of calcium hydroxyapatite.

The blood flow in the periodontal ligament regulated by the sympathetic and sensory nerves in the cat.

PubMed

Karita, K; Izumi, H; Tabata, T; Kuriwada, S; Sasano, T; Sanjo, D

1989-01-01

This study was carried out to investigate the nervous control of the blood flow in the periodontal ligament measured by laser Doppler flowmeter. Ten adult cats were anesthetized with pentobarbital sodium (initial dose of 30 mg/kg, i.v. and maintenance dose of 5 mg/kg, i.v.). After enucleating the left eye ball, the superior alveolar nerve was exposed. The bone overlying the labial aspect of the left maxillary canine tooth root was pared away until a transparent layer of bone was left covering the periodontal ligament. A laser light from a probe of the flowmeter fixed at the tooth was beamed through the thinned bone. Three different patterns of responses were observed following the electrical stimulation of the distal end of the cut superior alveolar nerve: an increasing, a decreasing and a biphasic change of blood flow. The application of capsaicin onto the superior alveolar nerve reduced the response of blood flow increase but had no effect on the response of blood flow decrease. On the other hand, the response of blood flow decrease was completely inhibited by the pretreatment with phentolamine while the response of blood flow increase was not affected. The present results suggest that blood flow in the periodontal ligament of cats is controlled by sympathetic alpha-adrenergic fibers for vasoconstriction and by sensory fibers for vasodilation.

Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.

PubMed

Webb, Emma A; Balasubramanian, Meena; Fratzl-Zelman, Nadja; Cabral, Wayne A; Titheradge, Hannah; Alsaedi, Atif; Saraff, Vrinda; Vogt, Julie; Cole, Trevor; Stewart, Susan; Crabtree, Nicola J; Sargent, Brandi M; Gamsjaeger, Sonja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus; Shaw, Nick J; Marini, Joan C; Högler, Wolfgang

2017-06-01

Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Clinical and bone material phenotype description and osteoblast differentiation studies. Natural history study in pediatric research centers. Eight patients with type XIV OI. Clinical examinations included bone mineral density, radiographs, echocardiography, and muscle biopsy. Bone biopsy samples (n = 3) were analyzed using histomorphometry, quantitative backscattered electron microscopy, and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Type XIV OI clinical phenotype ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband lumbar spine bone density z score was reduced [median -3.3 (range -4.77 to +0.1; n = 7)] and increased by +1.7 (1.17 to 3.0; n = 3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast, and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased expression of late and mineralization-related markers. Predominance of trimeric intracellular cation channel type B over type A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. OI type XIV has a bone histology, matrix mineralization, and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities. Copyright © 2017 Endocrine Society

Histological evolution of the regenerate during bone transport: an experimental study in sheep.

PubMed

López-Pliego, Esperanza Macarena; Giráldez-Sánchez, Miguel Ángel; Mora-Macías, Juan; Reina-Romo, Esther; Domínguez, Jaime

2016-09-01

Bone transport (BT) for segmentary bone defects is a well-known technique as it enables correction with new bone formation, which is similar to the previous bone. Despite the high number of experimental studies of distraction osteogenesis in bone lengthening, the types of ossification and histological changes that occur in the regenerate of the bone transport process remain controversial. The aim of this study is to provide the complete evolution of tissues and the types of ossification in the regenerate during the different phases of bone formation after BT until the end of the remodelling period. A histological study was performed using ten adult sheep that were submitted to BT. The types of ossification as well as the evolution of different tissues in the regenerate were determined using histomorphometry and inmunohistochemical studies. The evolution of trabeculae thickness, osteoblast and osteoclast densities, relationship between collagen types and changes in vascularization were also studied. Ossification was primarily intramembranous, with some focus of endochondral ossification in isolated animals. The cell counts showed a progression of cellular activity from the periphery to the centre, presenting the same progression as the growth of bone trabeculae, whose trabeculae thickness was quadrupled at the end of remodelling. Inmunohistochemical studies confirmed the prevalence of type I collagen and the ratio of the Type I/Type II collagen ratio was found to be 2.48. The percentages of the vascularized areas were proximally higher than distally in all animals, but distal zone obtained higher rates than the central region. Bone transport regenerate exhibits a centripetal ossification model and a mixed pattern with predominance of intramembranous over endochondral ossification. The data obtained resemble partially to those found in models of bone lengthening applied to large animals. This study provides a detailed structural characterization of the newly formed tissue, which may help to explain the development of the regenerate of bone transport in humans. It will also serve for future mechanobiological models that may aid research on the effect of loading or distractor stiffness in clinical results. © 2016 Elsevier Ltd. All rights reserved.

Evaluating differential nuclear DNA yield rates and osteocyte numbers among human bone tissue types: A synchrotron radiation micro-CT approach.

PubMed

Andronowski, Janna M; Mundorff, Amy Z; Pratt, Isaac V; Davoren, Jon M; Cooper, David M L

2017-05-01

Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren's (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for a scale of analysis that revealed a high range of variation in lacunar abundance in both tissue types. Moreover, high-resolution SR micro-CT imaging revealed potential soft tissue remnants within marrow spaces not visible macroscopically. It is hypothesized that soft tissue remnants observed among the trabeculae of skeletal elements with high quantities of cancellous bone tissue are responsible for the high nuclear DNA yields. These findings have significant implications for bone-sample selection for nuclear DNA analysis in a forensic context when skeletal remains are recovered from the ground surface. Copyright © 2017 Elsevier B.V. All rights reserved.

Exaggerated inflammatory response after use of recombinant bone morphogenetic protein in recurrent unicameral bone cysts.

PubMed

MacDonald, Kevin M; Swanstrom, Morgan M; McCarthy, James J; Nemeth, Blaise A; Guliani, Teresa A; Noonan, Kenneth J

2010-03-01

Recurrent unicameral bone cysts (UBCs) can result in significant morbidity during a child's physical and emotional development. Multiple treatment options are available and a review of the literature fails to clearly define the optimal treatment for UBCs. Recombinant bone morphogenetic protein (BMP) has been used with success in other disorders of poor bone formation. This manuscript is the first to report on the use of recombinant BMP in the treatment of UBCs. Three patients with recurrent UBCs underwent revision surgery with recombinant BMP. Radiographic and medical review was performed and is reported here. In these patients, the use of BMP failed to fully resolve their UBC; 2 patients had complete recurrence that required further surgery. In addition to poor radiographic results, all patients developed exaggerated inflammatory responses in the acute postoperative period. Each child developed clinically significant limb swelling and pain that mimicked infection. On the basis of our poor radiographic results and a paradoxical clinical result, we no longer recommend the use of recombinant BMP in the manner reported here for the treatment of recurrent UBCs. Level IV, case series.

Ultrastructural sinusoidal changes in extrahepatic cholestasis. Light and electron microscopic immunohistochemical localization of collagen type III and type IV.

PubMed

Gulubova, M V

1996-07-01

Extrahepatic cholestasis causes excessive extracellular matrix formation perisinusoidally. Ito cells, transitional and endothelial cells are considered to be a source of extracellular matrix proteins in experimental cholestasis. The localization of collagens type III and type IV in human liver in extrahepatic cholestasis was investigated immunohistochemically in the present study. Immersion fixation was used after modification to be applied to surgical biopsies with commercially available kits. Sinusoidal changes were observed that indicated excessive collagen and matrix formation. Light microscopically, increased immunostaining with the two collagen antibodies was found perisinusoidally and portally. Ultrastructurally, collagen type III positive fibres were found beneath basement membranes of vessels, in collagen bundles and as a fibrillar network in the space of Disse. Collagen type IV immunostaining was located in portal tracts and near hepatocyte microvilli. Intracellular staining with collagen type IV was detected in the rough endoplasmic reticulum of some transitional cells. Immunostaining was located around transitional cells, Ito cells or endothelial cells mainly. Our study indicates that Ito cells, transitional and endothelial cells are the main source of collagens type III and IV in the space of Disse in extrahepatic cholestasis in humans.

Oxygen microprofile in the prepared sediments and its implication for the sediment oxygen consuming process in a heavily polluted river of China.

PubMed

Wang, Chao; Zhai, Wanying; Shan, Baoqing

2016-05-01

Dissolved oxygen (DO) microprofiles of prepared sediments from 24 sampling sites in the Fuyang River were measured using a gold amalgam microelectrode in this study. The measured microprofiles can be divided into four types. In type I profiles, DO kept constant in the overlying water and decreased smoothly in the pore water; in type II profile, DO showed fluctuation in the pore water; in type III profiles, DO showed peak in the SWI; in type IV profiles, DO decreased obviously in the overlying water. Type I profiles indicated the absence of benthic organisms and thus the degradation of the sediment habitat. Type II and III profiles indicated the activity of benthic animal and epipelic algae, which is common in the healthy aquatic sediment. Type IV profiles indicated that the excessive accumulation of pollutants in the sediment and thus the serious sediment pollution. There are nine sites showing type I profile, three sites showing type II profile, nine sites showing type III profile, and three sites showing type IV profile in the Fuyang River. The dominance of type I and appearance of type IV indicated that sediment oxygen consumption processes in the Fuyang River were strongly influenced by the sediment pollutants release and the vanish of benthic organisms. The pharmacy, metallurgy, and curriery industries may contribute to the sediment deterioration and thus to the occurrence of type I and type IV oxygen profiles in the Fuyang River.

Is osteoporosis a peculiar association with primary biliary cirrhosis?

PubMed Central

Floreani, Annarosa; Mega, Andrea; Camozzi, Valentina; Baldo, Vincenzo; Plebani, Mario; Burra, Patrizia; Luisetto, Giovanni

2005-01-01

AIM: (1) To compare the prevalence of osteoporosis (t-score ≤ -2.5 SD) between stage IV PBC patients, and two groups of age- and sex-matched controls: one with hepatitis C virus (HCV)-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population; (2) to identify the main risk factors for the development of bone loss. METHODS: Thirty-five stage IV PBC patients (mean age 52.5 ± 10 years), 49 females with HCV-related cirrhosis (mean age 52.9 ± 5.8 years) and 33 healthy females (mean age 51.8 ± 2.22 years) were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin (Ca corr.), 25-hydroxy vitamin D (25-OH vit D), parathyroid hormone, osteocalcin. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS: Osteoporosis was present in 5/35 PBC patients (14.2%) and in 7/49 HCV-related cirrhotic patients (14.3%), without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI < 23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION: PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age. PMID:16149144

Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

ClinicalTrials.gov

2017-11-29

Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Fanconi Anemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Waldenström Macroglobulinemia

Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome

PubMed Central

Kim, Jeong Gyun; Cho, Won-Sang; Kim, Jeong Eun

2014-01-01

Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure. PMID:24653803

Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome.

PubMed

Kim, Jeong Gyun; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Jeong Eun

2014-02-01

Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.

Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency

PubMed Central

Xiong, Jinhu; Piemontese, Marilina; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2014-01-01

Parathyroid hormone (PTH) excess stimulates bone resorption. This effect is associated with increased expression of the osteoclastogenic cytokine receptor activator of nuclear factor кB ligand (RANKL) in bone. However, several different cell types, including bone marrow stromal cells, osteocytes, and T lymphocytes, express both RANKL and the PTH receptor and it is unclear whether RANKL expression by any of these cell types is required for PTH-induced bone loss. Here we have used mice lacking the RANKL gene in osteocytes to determine whether RANKL produced by this cell type is required for the bone loss caused by secondary hyperparathyroidism induced by dietary calcium deficiency in adult mice. Thirty days of dietary calcium deficiency caused bone loss in control mice, but this effect was blunted in mice lacking RANKL in osteocytes. The increase in RANKL expression in bone and the increase in osteoclast number caused by dietary calcium deficiency were also blunted in mice lacking RANKL in osteocytes. These results demonstrate that RANKL produced by osteocytes contributes to the increased bone resorption and the bone loss caused by secondary hyperparathyroidism, strengthening the evidence that osteocytes are an important target cell for hormonal control of bone remodeling. PMID:24933342

A new system for cultivation of human keratinocytes on acellular dermal matrix substitute with the use of human fibroblast feeder layer.

PubMed

Xiao, S; Zhu, S; Ma, B; Xia, Z-F; Yang, J; Wang, G

2008-01-01

To improve the proliferative potential of human keratinocytes (HK) cultured on acellular dermal matrix (ADM), HK and mitomycin C-treated human fibroblasts (MMC-HF) were seeded onto ADM to form four types of composite skin: type I, HK were seeded onto the epidermal side of ADM; type II, both HK and MMC-HF were seeded onto the epidermal side; type III, MMC-HF were preseeded onto the dermal side of ADM, and then HK were seeded onto the epidermal side, and type IV, where MMC-HF were preseeded onto both sides, and then HK were seeded onto the epidermal side. Compared with type I and III, the proliferative potential of HK of type II and IV was significantly higher on day 3, 5, 7 and 9 in vitro. In type I and III, HK grew into one layer on day 7-9, while in type II and IV keratinocytes grew into a confluent monolayer by day 4-6. The adherence to ADM of HK in types II and IV was stronger than that in type I and III. The take rate of type II and IV composite skin was also significantly higher. In conclusion, when MMC-HF and HK were cocultured on the epidermal side of ADM, MMC-HF could serve as excellent feeder cells. Copyright 2007 S. Karger AG, Basel.

Ultraviolet properties of IRAS-selected Be stars

NASA Technical Reports Server (NTRS)

Bjorkman, Karen S.; Snow, Theodore P.

1988-01-01

New IUE observations were obtained of 35 Be stars from a list of stars which show excess infrared fluxes in IRAS data. The IRAS-selected Be stars show larger C IV and Si IV equivalent widths than other Be stars. Excess C IV and Si IV absorption seems to be independent of spectral type for IRAS-selected Be stars later than spectral type B4. This is interpreted as evidence for a possible second mechanism acting in conjunction with radiation pressure for producing the winds in Be stars. No clear correlation of IR excess of v sin i with C IV or Si IV equivalent widths is seen, although a threshold for the occurrence of excess C IV and Si IV absorption appears at a v sin i of 150 km/sec.

Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

PubMed

Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

2013-05-15

This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption.

Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

PubMed

Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

2017-11-01

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

Are bone turnover markers capable of predicting callus consolidation during bone healing?

PubMed

Klein, P; Bail, H J; Schell, H; Michel, R; Amthauer, H; Bragulla, H; Duda, G N

2004-07-01

The aim of this study was to determine the ability of the following bone turnover markers to monitor the course of callus consolidation during bone healing: Carboxy-terminal propeptide of procollagen type I (PICP), skeletal alkaline phosphatase (sALP), and amino-terminal propeptide of type III procollagen (PIlINP). Since interfragmentary movements have been proven to possess the ability to document the progression of bone healing in experimental studies, correlations between bone turnover markers and interfragmentary movements in vivo were investigated. Therefore, two different types of osteosyntheses representing different mechanical situations at the fracture site were compared in an ovine osteotomy model. Blood samples were taken preoperatively and postoperatively in weekly intervals over a nine-week healing period. At the same intervals, interfragmentary movements were measured in all sheep. After nine weeks, animals were sacrificed and the tibiae were evaluated both mechanically and histologically. Wide interindividual ranges were observed for all bone turnover markers. The systemic PICP level did not increase with callus consolidation. The bone-healing model seemed to influence the systemic level of PIIINP and sALP but no general correlation between bone turnover markers and interfragmentary movements could be detected. No differences between the different types of osteosyntheses and thus the different mechanical situations were observed. All analyzed markers failed as general predictors for the course of callus consolidation during bone healing.

Genetics Home Reference: congenital insensitivity to pain with anhidrosis

MedlinePlus

... is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA ... to pain with anhidrosis hereditary sensory and autonomic neuropathy type IV hereditary sensory and autonomic neuropathy, type ...

Reverse total shoulder replacement for nonunion of a fracture of the proximal humerus.

PubMed

Zafra, M; Uceda, P; Flores, M; Carpintero, P

2014-09-01

Patients with pain and loss of shoulder function due to nonunion of a fracture of the proximal third of the humerus may benefit from reverse total shoulder replacement. This paper reports a prospective, multicentre study, involving three hospitals and three surgeons, of 35 patients (28 women, seven men) with a mean age of 69 years (46 to 83) who underwent a reverse total shoulder replacement for the treatment of nonunion of a fracture of the proximal humerus. Using Checchia's classification, nine nonunions were type I, eight as type II, 12 as type III and six as type IV. The mean follow-up was 51 months (24 to 99). Post-operatively, the patients had a significant decrease in pain (p < 0.001), and a significant improvement in flexion, abduction, external rotation and Constant score (p < 0.001), but not in internal rotation. A total of nine complications were recorded in seven patients: six dislocations, one glenoid loosening in a patient who had previously suffered dislocation, one transitory paresis of the axillary nerve and one infection. Reverse total shoulder replacement may lead to a significant reduction in pain, improvement in function and a high degree of satisfaction. However, the rate of complications, particularly dislocation, was high. ©2014 The British Editorial Society of Bone & Joint Surgery.

Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate.

PubMed

Konttinen, Y T; Salo, T; Hanemaaijer, R; Valleala, H; Sorsa, T; Sutinen, M; Ceponis, A; Xu, J W; Santavirta, S; Teronen, O; López-Otín, C

1999-08-01

The hypothesis of the present work was that the pannus tissue overlying the articular hard tissues has an aggressive phenotype and contains the newly discovered collagenase-3 and its endogenous inducers and activators. We therefore analyzed the eventual presence of collagenase-3 and its regulation at the pannus-cartilage junction. Collagenase-3 mRNA (in situ hybridization) and enzyme protein (ABC and immunofluorescence staining) were found in the pannocytes in the pannus-hard tissue junction. Inflammatory round cells associated with the critical interface contained TNF-alpha and IL-1beta. These cytokines induced collagenase-3 secretion in cultured rheumatoid synovial fibroblasts. Procollagenase-3 activators, stromelysin-1, 72 kDa type IV collagenase/gelatinase and membrane-type 1-MMP, were also found in the pannus-hard tissue junction. Active collagenase-3 was inhibited with alendronate (IC50 = 500-750 microM). Collagenase-3, due to its substrate profile and local synthesis in a milieu favoring its activation, might play a major role in the degradation of cartilage type II and bone type I collagens. Alendronate, at concentrations attainable in vivo, is able to inhibit collagenase-3. This might offer an option to control collagenase-3-mediated tissue destruction in rheumatoid arthritis.

Collagen type IV at the fetal-maternal interface.

PubMed

Oefner, C M; Sharkey, A; Gardner, L; Critchley, H; Oyen, M; Moffett, A

2015-01-01

Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear. Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry. Col-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined. Col-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site. Copyright © 2014 Elsevier Ltd. All rights reserved.

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2012 CFR

2012-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2013 CFR

2013-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2014 CFR

2014-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2011 CFR

2011-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiu-Li, E-mail: usually.158@163.com; Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071; Peng, Chun-Wei, E-mail: pqc278@163.com

Highlights: {yields} HER2 level is closely related to the biologic behaviors of breast cancer cells. {yields} A new method to simultaneously image HER2 and type IV collagen was established. {yields} HER2 status and type IV collagen degradation predict breast cancer invasion. {yields} The complex interactions between tumor and its environment were revealed. -- Abstract: It has been well recognized that human epidermal growth factor receptor 2 (HER2) level in breast cancer (BC) is closely related to the malignant biologic behaviors of the tumor, including invasion and metastasis. Yet, there has been a lack of directly observable evidence to support suchmore » notion. Here we report a quantum dots (QDs)-based double-color imaging technique to simultaneously show the HER2 level on BC cells and the type IV collagen in the tumor matrix. In benign breast tumor, the type IV collagen was intact. With the increasing of HER2 expression level, there has been a progressive decrease in type IV collagen around the cancer nest. At HER2 (3+) expression level, there has virtually been a total destruction of type IV collagen. Moreover, HER2 (3+) BC cells also show direct invasion into the blood vessels. This novel imaging method provides direct observable evidence to support the theory that the HER2 expression level is directly related to BC invasion.« less

Operative treatment of intra-articular calcaneal fractures with calcaneal plates and its complications

PubMed Central

Rak, Vaclav; Ira, Daniel; Masek, Michal

2009-01-01

Background: In a retrospective study we analysed intra-articular calcaneal fracture treatment by comparing results and complications related to fracture stabilization with nonlocking calcaneal plates and locking compression plates. Materials and Methods: We performed 76 osteosynthesis (67 patients) of intra-articular calcaneal fractures using the standard extended lateral approach from February 2004 to October 2007. Forty-two operations using nonlocking calcaneal plates (group A) were performed during the first three years, and 34 calcaneal fractures were stabilized using locking compression plates (group B) in 2007. In the Sanders type IV fractures, reconstruction of the calcaneal shape was attempted. Depending on the type of late complication, we performed subtalar arthroscopy in six cases, arthroscopically assisted subtalar distraction bone block arthrodesis in six cases, and plate removal with lateral-wall decompression in five cases. The patients were evaluated by the AOFAS Ankle-Hindfoot Scale. Results: Wound healing complications were 7/42 (17%) in group A and 1/34 (3%) in group B. No patient had deep osseous infection or foot rebound compartment syndrome. Preoperative size of Böhler's angle correlated with postoperative clinical results in both groups. There were no late complications necessitating corrective procedure or arthroscopy until December 2008 in Group B. All late complications ccurred in Group A. The overall results according to the AOFAS Ankle Hindfoot Scale were good or excellent in 23/42 (55%) in group A and in 30/34 (85%) in group B. Conclusion: Open reduction and internal fixation of intra-articular calcaneal fractures has become a standard surgical method. Fewer complications and better results related to treatment with locking compression plates confirmed in comparison to nonlocking ones were noted for all Sanders types of intra-articular calcaneal fractures. Age and Sanders type IV fractures are not considered to be the contraindications to surgery. PMID:19838350

On the Directivity of Low-Frequency Type IV Radio Bursts

NASA Technical Reports Server (NTRS)

Gopalswamy, N.; Akiyama, S.; Makela, P.; Yashiro, S.; Cairns, I. H.

2016-01-01

An intense type IV radio burst was observed by the STEREO Behind (STB) spacecraft located about 144 deg. behind Earth. The burst was associated with a large solar eruption that occurred on the backside of the Sun (N05E151) close to the disk center in the STB view. The eruption was also observed by the STEREO Ahead (STA) spacecraft (located at 149 deg. ahead of Earth) as an eruption close to the west limb (N05W60) in that view. The type IV burst was complete in STB observations in that the envelope reached the lowest frequency and then receded to higher frequencies. The burst was partial viewed from STA, revealing only the edge coming down to the lowest frequency. The type IV burst was not observed at all near Earth because the source was 61 deg. behind the east limb. The eruption was associated with a low-frequency type II burst observed in all three views, although it was not very intense. Solar energetic particles were also observed at both STEREOs and at SOHO, suggesting that the shock was much extended, consistent with the very high speed of the CME (2048 km/s). These observations suggest that the type IV emission is directed along a narrow cone above the flare site. We confirm this result statistically using the type IV bursts of solar cycle 23.

Deposition of collagen type I onto skeletal endothelium reveals a new role for blood vessels in regulating bone morphology

PubMed Central

Ben Shoham, Adi; Rot, Chagai; Stern, Tomer; Krief, Sharon; Akiva, Anat; Dadosh, Tali; Sabany, Helena; Lu, Yinhui; Kadler, Karl E.

2016-01-01

Recently, blood vessels have been implicated in the morphogenesis of various organs. The vasculature is also known to be essential for endochondral bone development, yet the underlying mechanism has remained elusive. We show that a unique composition of blood vessels facilitates the role of the endothelium in bone mineralization and morphogenesis. Immunostaining and electron microscopy showed that the endothelium in developing bones lacks basement membrane, which normally isolates the blood vessel from its surroundings. Further analysis revealed the presence of collagen type I on the endothelial wall of these vessels. Because collagen type I is the main component of the osteoid, we hypothesized that the bone vasculature guides the formation of the collagenous template and consequently of the mature bone. Indeed, some of the bone vessels were found to undergo mineralization. Moreover, the vascular pattern at each embryonic stage prefigured the mineral distribution pattern observed one day later. Finally, perturbation of vascular patterning by overexpressing Vegf in osteoblasts resulted in abnormal bone morphology, supporting a role for blood vessels in bone morphogenesis. These data reveal the unique composition of the endothelium in developing bones and indicate that vascular patterning plays a role in determining bone shape by forming a template for deposition of bone matrix. PMID:27621060

Early prophylactic autogenous bone grafting in type III open tibial fractures.

PubMed

Kesemenli, Cumhur C; Kapukaya, Ahmet; Subaşi, Mehmet; Arslan, Huseyin; Necmioğlu, Serdar; Kayikçi, Cuma

2004-08-01

The authors report the results achieved in patients with type III open tibial fractures who underwent primary autogenous bone grafting at the time of debridement and skeletal stabilisation. Twenty patients with a mean age of 35.8 years (range, 24-55) were treated between 1996 and 1999. Eight fractures were type IIIA, 11 were type IIIB, and 1 was type IIIC. At the index procedure, wound debridement, external fixation and autogenous bone grafting with bone coverage were achieved. The mean follow-up period was 46 months (range, 34-55). The mean time to fixator removal was 21 weeks (range, 14-35), and the mean time to union was 28 weeks (range, 19-45). Skin coverage was achieved by a myocutaneous flap in 2 patients, late primary closure in 4, and split skin grafting in 14. One (5%) of the patients experienced delayed union, and 1 (5%) developed infection. In tibial type III open fractures, skin coverage may be delayed, using the surrounding soft tissue to cover any exposed bone after thorough débridement and wound cleansing. Primary prophylactic bone grafting performed at the same time reduces the rate of delayed union, shortens the time to union, and does not increase the infection rate.

Effect of framework material and vertical misfit on stress distribution in implant-supported partial prosthesis under load application: 3-D finite element analysis.

PubMed

Bacchi, Ataís; Consani, Rafael Leonardo Xediek; Mesquita, Marcelo Ferraz; Dos Santos, Mateus Bertolini Fernandes

2013-09-01

This study evaluated the influence of framework material and vertical misfit on stress created in an implant-supported partial prosthesis under load application. The posterior part of a severely reabsorbed jaw with a fixed partial prosthesis above two osseointegrated titanium implants at the place of the second premolar and second molar was modeled using SolidWorks 2010 software. Finite element models were obtained by importing the solid model into an ANSYS Workbench 11 simulation. The models were divided into 15 groups according to their prosthetic framework material (type IV gold alloy, silver-palladium alloy, commercially pure titanium, cobalt-chromium alloy or zirconia) and vertical misfit level (10 µm, 50 µm and 100 µm). After settlement of the prosthesis with the closure of the misfit, simultaneous loads of 110 N vertical and 15 N horizontal were applied on the occlusal and lingual faces of each tooth, respectively. The data was evaluated using Maximum Principal Stress (framework, porcelain veneer and bone tissue) and a von Mises Stress (retention screw) provided by the software. As a result, stiffer frameworks presented higher stress concentrations; however, these frameworks led to lower stresses in the porcelain veneer, the retention screw (faced to 10 µm and 50 µm of the misfit) and the peri-implant bone tissues. The increase in the vertical misfit resulted in stress values increasing in all of the prosthetic structures and peri-implant bone tissues. The framework material and vertical misfit level presented a relevant influence on the stresses for all of the structures evaluated.

[Assessment of the hearing results in tympanoplasties with the use of palisade-technique].

PubMed

Wielgosz, Romuald; Mroczkowski, Edward

2006-01-01

The cartilage has been successfuly used in reconstructive ear surgery for more than one hundred years. Histologic study of autografts cartilage (tragal or conchal) showed good long-term preservation of cartilage cells. The aim of this paper is to assess the hearing results in tympanoplasties with the use of cartilage palisade technique. The retrospective analysis concerned 108 operated clinical cases. The cartilage palisade technique was performed in 28 tympanoplasties type I, 47 tympanoplasties type II, 21 tympanoplasties type III with columella and in 2 tympanoplasties type IV. Clinical assessment included otoscopy, test for eustachian tube ventilation, test with tuning fork, audiometry on a range 0,5, 1, 2 kHz and subjective evaluation based on questionaire. The Air Bone Gap (ABG) was noted as follows: < 10 dB among 67,8% of patients and 11-20 dB among 21,4% of patients in tympanoplasty type I. In tympanoplasty type II the ABG was responsively: < 10 dB - 80% patients, 11-20 dB - 10% patients. In the type III of tympanoplasty 40,4% of patients showed ABG < 10 dB and 42,5% of patients 11-20 dB. In the type III with columella we noted 15% patients with ABG < 10 dB and 65% of them with ABG 11-20 dB. The cartilage is a good autograft for reconstruction of the tympanic membrane, middle ear and the auditory wall because of stability and lack of secondary perforations. Long-term results in hearing are also satisfactory.

Association of Glycemic Status with Bone Turnover Markers in Type 2 Diabetes Mellitus.

PubMed

Kulkarni, Sweta Vilas; Meenatchi, Suruthi; Reeta, R; Ramesh, Ramasamy; Srinivasan, A R; Lenin, C

2017-01-01

Type 2 diabetes mellitus has profound implications on the skeleton. Even though bone mineral density is increased in type 2 diabetes mellitus patients, they are more prone for fractures. The weakening of bone tissue in type 2 diabetes mellitus can be due to uncontrolled blood sugar levels leading to high levels of bone turnover markers in blood. The aim of this study is to find the association between glycemic status and bone turnover markers in type 2 diabetes mellitus. This case-control study was carried out in a tertiary health care hospital. Fifty clinically diagnosed type 2 diabetes mellitus patients in the age group between 30 and 50 years were included as cases. Fifty age- and gender-matched healthy nondiabetics were included as controls. Patients with complications and chronic illness were excluded from the study. Depending on glycated hemoglobin (HbA1c) levels, patients were grouped into uncontrolled (HbA1c >7%, n = 36) and controlled (HbA1c <7%, n = 14) diabetics. Based on duration of diabetes, patients were grouped into newly diagnosed, 1-2 years, 3-5 years, and >5 years. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), acid phosphatase (ACP), and HbA1c levels were estimated. OC/BAP and OC/ACP ratio was calculated. Student's t -test, analysis of variance, and Chi-square tests were used for analysis. Receiver operating characteristic (ROC) curve analysis was done for OC/BAP and OC/ACP ratios. Serum OC, HbA1c, and OC/BAP ratio were increased in cases when compared to controls and were statistically significant ( P < 0.001). OC/ACP ratio was decreased in type 2 diabetes mellitus and was statistically significant ( P = 0.01). In patients with >5-year duration of diabetes, HbA1c level was high and was statistically significant ( P < 0.042). BAP levels were high in uncontrolled diabetics but statistically not significant. ROC curve showed OC/BAP ratio better marker than OC/ACP ratio. Uncontrolled type 2 diabetes mellitus affects bone tissue resulting in variations in bone turnover markers. Bone turnover markers are better in predicting recent changes in bone morphology and are cost effective.

Distribution of Type I Collagen Morphologies in Bone: Relation to Estrogen Depletion

PubMed Central

Wallace, Joseph M.; Erickson, Blake; Les, Clifford M.; Orr, Bradford G.; Holl, Mark M. Banaszak

2009-01-01

Bone is an amazing material evolved by nature to elegantly balance structural and metabolic needs in the body. Bone health is an integral part of overall health, but our lack of understanding of the ultrastructure of healthy bone precludes us from knowing how disease may impact nanoscale properties in this biological material. Here, we show that quantitative assessments of a distribution of Type I collagen fibril morphologies can be made using atomic force microscopy (AFM). We demonstrate that normal bone contains a distribution of collagen fibril morphologies and that changes in this distribution can be directly related to disease state. Specifically, by monitoring changes in the collagen fibril distribution of sham-operated and estrogen-depleted sheep, we have shown the ability to detect estrogen-deficiency-induced changes in Type I collagen in bone. This discovery provides new insight into the ultrastructure of bone as a tissue and the role of material structure in bone disease. The observation offers the possibility of a much-needed in vitro procedure to complement the current methods used to diagnose osteoporosis and other bone disease. PMID:19932773

Assessing bone banking activities at University of Malaya medical centre.

PubMed

Mohd, Suhaili; Samsuddin, Sharifah Mazni; Ramalingam, Saravana; Min, Ng Wuey; Yusof, Norimah; Zaman, T Kamarul; Mansor, Azura

2015-12-01

The main advantage of establishing in-house bone banks is its ability to readily provide allograft bones for local surgeries. Bone procurement activities of our university bone bank during the 10 years of operation were reviewed. Socio-demographic data of donors, types of bone procured, cases of rejected bones and types of allograft bones transplanted are presented. From 179 potential donors, 73 % were accepted with 213 procured bones. Femoral head was the common bone transplanted (45 %), as it was also the most common procured (82 %). Bones were rejected mainly due to non-technical reasons (83 %) rather than positive results of microbiological (13 %) and serological (4 %) tests. Comprehensive data could not be obtained for further analysis due to difficulties in retrieving information. Therefore, quality assurance system was improved to establish more systematic documentations, as the basis of good banking practice with process control hence allowing traceability.

Bone turnover marker reference intervals in young females.

PubMed

Callegari, Emma T; Gorelik, Alexandra; Garland, Suzanne M; Chiang, Cherie Y; Wark, John D

2017-07-01

Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131  µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.

Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice.

PubMed

Turgeman, Gadi; Zilberman, Yoram; Zhou, Shuanhu; Kelly, Pam; Moutsatsos, Ioannis K; Kharode, Yogendra P; Borella, Luis E; Bex, Frederick J; Komm, Barry S; Bodine, Peter V N; Gazit, Dan

2002-01-01

Osteoporosis is a disease manifested in drastic bone loss resulting in osteopenia and high risk for fractures. This disease is generally divided into two subtypes. The first, post-menopausal (type I) osteoporosis, is primarily related to estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related to aging. Decreased bone formation, as well as increased bone resorption and turnover, are thought to play roles in the pathophysiology of both types of osteoporosis. In this study, we demonstrate in murine models for both type I (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced bone formation is related to a decrease in adult mesenchymal stem cell (AMSC) number, osteogenic activity, and proliferation. Decreased proliferation is coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice. Recombinant human bone morphogenetic protein (rhBMP-2) is a highly osteoinductive protein, promoting osteogenic differentiation of AMSCs. Systemic intra-peritoneal (i.p.) injections of rhBMP-2 into osteopenic mice were able to reverse this phenotype in the bones of these animals. Moreover, this change in bone mass was coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation as well as a decrease in apoptosis. Bone formation activity was increased as well. However, the magnitude of this response to rhBMP-2 varied among different stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model), rhBMP-2 systemic treatment also restored both articular and epiphyseal cartilage width to the levels seen in young mice. In summary, our study shows that AMSCs are a good target for systemically active anabolic compounds like rhBMP-2. Copyright 2002 Wiley-Liss, Inc.

Type IV carbonic anhydrase is present in the gills of spiny dogfish (Squalus acanthias).

PubMed

Gilmour, K M; Bayaa, M; Kenney, L; McNeill, B; Perry, S F

2007-01-01

Physiological and biochemical studies have provided indirect evidence for a membrane-associated carbonic anhydrase (CA) isoform, similar to mammalian type IV CA, in the gills of dogfish (Squalus acanthias). This CA isoform is linked to the plasma membrane of gill epithelial cells by a glycosylphosphatidylinositol anchor and oriented toward the plasma, such that it can catalyze the dehydration of plasma HCO(3)(-) ions. The present study directly tested the hypothesis that CA IV is present in dogfish gills in a location amenable to catalyzing plasma HCO(3)(-) dehydration. Homology cloning techniques were used to assemble a 1,127 base pair cDNA that coded for a deduced protein of 306 amino acids. Phylogenetic analysis suggested that this protein was a type IV CA. For purposes of comparison, a second cDNA (1,107 base pairs) was cloned from dogfish blood; it encoded a deduced protein of 260 amino acids that was identified as a cytosolic CA through phylogenetic analysis. Using real-time PCR and in situ hybridization, mRNA expression for the dogfish type IV CA was detected in gill tissue and specifically localized to pillar cells and branchial epithelial cells that flanked the pillar cells. Immunohistochemistry using a polyclonal antibody raised against rainbow trout type IV CA revealed a similar pattern of CA IV immunoreactivity and demonstrated a limited degree of colocalization with Na(+)-K(+)-ATPase immunoreactivity. The presence and localization of a type IV CA isoform in the gills of dogfish is consistent with the hypothesis that branchial membrane-bound CA with an extracellular orientation contributes to CO(2) excretion in dogfish by catalyzing the dehydration of plasma HCO(3)(-) ions.

Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder.

PubMed

Kadriu, B; Gold, P W; Luckenbaugh, D A; Lener, M S; Ballard, E D; Niciu, M J; Henter, I D; Park, L T; De Sousa, R T; Yuan, P; Machado-Vieira, R; Zarate, C A

2017-05-30

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 min, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels, and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.Molecular Psychiatry advance online publication, 30 May 2017; doi:10.1038/mp.2017.109.

The prevalence of the sesamoid bones of the hand: a systematic review and meta-analysis.

PubMed

Yammine, Kaissar

2014-11-01

The literature contains various estimates of the prevalence and distribution of the sesamoid bones in the hands. The aims of this systematic review are to provide a better estimate of the frequency of hand sesamoids and its association with variables such as ancestry, gender, and side. Nineteen studies met the inclusion criteria. The pooled rates of the sensitive meta-analyses from large-sample studies in adults showed: (a) true overall rates of 99.9% for the metacarpophalangeal (MCP) joint of the thumb (MCP-I), 53% for the interphalangeal joint (IP-I), 43.4% for the MCP of the index (MCP-II), 1.47% for the MCP of the medius finger (MCP-III), 0.6% for the MCP of the ring finger (MCP-IV), and 67.7% for the MCP of the auricular finger (MCP-V); (b) true radiological rates of 99.9% for the radial thumb sesamoid, 99.6% for the ulnar thumb sesamoid, 47.8% for IP-I, 40% for MCP-II, 1.3% for MCP-III, 0.8% for MCP-VI, and 62.8% for MCP-V. Black, Middle Eastern, and European ancestries conferred significantly higher sesamoid frequencies at IP-I, MCP-II, and MCP-V, respectively. There was a significant association with female gender at MCP-II, MCP-IV, and MCP-V, with ORs of 1.53, 4, and 1.3, respectively, and a nonsignificant "female" trend for the other locations. There was no significant association with hand side. The pooled rates of hand sesamoids in children aged 10-17 years were 92.7, 42.2, 33.8, 0.5, 0.3, and 36.5% for MCP-I, IP-I, MCP-II, MCP-III, MCP-IV, and MCP-V, respectively. The findings of this evidence-based anatomical review provide quantitative evidence that the incidence of sesamoid bones in human hands depends on genetic rather than functional factors. © 2014 Wiley Periodicals, Inc.

Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone☆

PubMed Central

Vanleene, Maximilien; Shefelbine, Sandra J.

2013-01-01

Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45 Hz, 0.3 g, 15 minutes/days, 5 days/week) in young OI (oim) and wild type female mice from 3 to 8 weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the histological sections, it is possible that WBV reduced bone resorption, resulting in a relative increase in cortical thickness. Whole body vibration appears as a potential effective and innocuous means for increasing bone formation and strength, which is particularly attractive for treating the growing skeleton of children suffering from brittle bone disease or low bone density pathologies without the long term disadvantages of current pharmacological therapies. PMID:23352925

Does cortical bone thickness in the last sacral vertebra differ among tail types in primates?

PubMed

Nishimura, Abigail C; Russo, Gabrielle A

2017-04-01

The external morphology of the sacrum is demonstrably informative regarding tail type (i.e., tail presence/absence, length, and prehensility) in living and extinct primates. However, little research has focused on the relationship between tail type and internal sacral morphology, a potentially important source of functional information when fossil sacra are incomplete. Here, we determine if cortical bone cross-sectional thickness of the last sacral vertebral body differs among tail types in extant primates and can be used to reconstruct tail types in extinct primates. Cortical bone cross-sectional thickness in the last sacral vertebral body was measured from high-resolution CT scans belonging to 20 extant primate species (N = 72) assigned to tail type categories ("tailless," "nonprehensile short-tailed," "nonprehensile long-tailed," and "prehensile-tailed"). The extant dataset was then used to reconstruct the tail types for four extinct primate species. Tailless primates had significantly thinner cortical bone than tail-bearing primates. Nonprehensile short-tailed primates had significantly thinner cortical bone than nonprehensile long-tailed primates. Cortical bone cross-sectional thickness did not distinguish between prehensile-tailed and nonprehensile long-tailed taxa. Results are strongly influenced by phylogeny. Corroborating previous studies, Epipliopithecus vindobonensis was reconstructed as tailless, Archaeolemur edwardsi as long-tailed, Megaladapis grandidieri as nonprehensile short-tailed, and Palaeopropithecus kelyus as nonprehensile short-tailed or tailless. Results indicate that, in the context of phylogenetic clade, measures of cortical bone cross-sectional thickness can be used to allocate extinct primate species to tail type categories. © 2017 Wiley Periodicals, Inc.

Modified classification and single-stage microsurgical repair of posttraumatic infected massive bone defects in lower extremities.

PubMed

Yang, Yun-fa; Xu, Zhong-he; Zhang, Guang-ming; Wang, Jian-wei; Hu, Si-wang; Hou, Zhi-qi; Xu, Da-chuan

2013-11-01

Posttraumatic infected massive bone defects in lower extremities are difficult to repair because they frequently exhibit massive bone and/or soft tissue defects, serious bone infection, and excessive scar proliferation. This study aimed to determine whether these defects could be classified and repaired at a single stage. A total of 51 cases of posttraumatic infected massive bone defect in lower extremity were included in this study. They were classified into four types on the basis of the conditions of the bone defects, soft tissue defects, and injured limb length, including Type A (without soft tissue defects), Type B (with soft tissue defects of 10 × 20 cm or less), Type C (with soft tissue defects of 10 × 20 cm or more), and Type D (with the limb shortening of 3 cm or more). Four types of single-stage microsurgical repair protocols were planned accordingly and implemented respectively. These protocols included the following: Protocol A, where vascularized fibular graft was implemented for Type A; Protocol B, where vascularized fibular osteoseptocutaneous graft was implemented for Type B; Protocol C, where vascularized fibular graft and anterior lateral thigh flap were used for Type C; and Protocol D, where limb lengthening and Protocols A, B, or C were used for Type D. There were 12, 33, 4, and 2 cases of Types A, B, C, and D, respectively, according to this classification. During the surgery, three cases of planned Protocol B had to be shifted into Protocol C; however, all microsurgical repairs were completed. With reference to Johner-Wruhs evaluation method, the total percentage of excellent and good results was 82.35% after 6 to 41 months of follow-up. It was concluded that posttraumatic massive bone defects could be accurately classified into four types on the basis of the conditions of bone defects, soft tissue coverage, and injured limb length, and successfully repaired with the single-stage repair protocols after thorough debridement. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Hedgehog Signaling in Tumor Induced Bone Disease

PubMed Central

Cannonier, Shellese A.; Sterling, Julie A.

2015-01-01

Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

PubMed

Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

2015-04-02

Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

Outcomes of Corneal Cross-Linking Correlate With Cone-Specific Lysyl Oxidase Expression in Patients With Keratoconus.

PubMed

Shetty, Rohit; Rajiv Kumar, Nimisha; Pahuja, Natasha; Deshmukh, Rashmi; Vunnava, KrishnaPoojita; Abilash, Valsala Gopalakrishnan; Sinha Roy, Abhijit; Ghosh, Arkasubhra

2018-03-01

To evaluate the correlation of visual and keratometry outcomes after corneal cross-linking (CXL) in patients with keratoconus with cone epithelium-specific gene expression levels. Corneal epithelium was obtained from 35 eyes that underwent accelerated CXL (KXLII, 9 mW/cm for 10 min). Using corneal topography, epithelium over the cone and periphery was obtained separately from each subject. The ratio of gene expression for lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), bone morphogenic protein 7, tissue inhibitor of metalloproteinase 1, collagen, type I, alpha 1, and collagen, type IV, alpha 1 (COL IVA1) from the cone and peripheral cornea was correlated with the outcome of cross-linking surgery. Patients were assessed for visual acuity, keratometry, refraction, and corneal densitometry before and 6 months after surgery. Based on the change in corneal flattening indicated by ΔKmax, the outcomes were classified as a higher response or lower response. Reduction in keratometric indices correlated with improved spherical equivalent after CXL. Preoperative levels of cone-specific LOX expression in cases with a higher response were significant (P = 0.001). COL IVA1, bone morphogenic protein 7, and tissue inhibitor of metalloproteinase 1 gene expressions were reduced in the cones of the subjects with a lower response. MMP9 levels were relatively lower in cases with a higher response compared with those with a lower response. Our study demonstrates that preoperative levels of molecular factors such as LOX, MMP9, and COL IVA1 aid in understanding CXL outcomes at the tissue level.

Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone.

PubMed

Garnero, Patrick; Borel, Olivier; Gineyts, Evelyne; Duboeuf, Francois; Solberg, Helene; Bouxsein, Mary L; Christiansen, Claus; Delmas, Pierre D

2006-03-01

Mechanical behavior of bone depends on its mass and architecture, and on the material properties of the matrix, which is composed of a mineral phase and an organic component mainly constituted of type I collagen. Mineral accounts largely for the stiffness of bone, whereas type I collagen provides bone its ductility and toughness, i.e., its ability to undergo deformation and absorb energy after it begins to yield. The molecular mechanisms underlying the effect of alterations in type I collagen on bone mechanical properties are unclear. We used an in vitro model of fetal bovine cortical bone specimens (n = 44), where the extent of type I collagen cross-linking was modified by incubation at 37 degrees C for 0, 60, 90 and 120 days, keeping constant the architecture and the mineral content. At each incubation time, the following parameters were determined: (1) the bone concentration of enzymatic (pyridinoline; PYD and deoxypyridinoline, DPD) and non-enzymatic (pentosidine) crosslinks by HPLC, (2) the extent of aspartic acid isomerization of the type I collagen C-telopeptide (CTX) by ELISA of native (alpha CTX) and isomerized (beta CTX) forms, (3) the mineral density by DXA, (4) the porosity by micro-computed tomography and (5) the bending and compressive mechanical properties. Incubation of bone specimens at 37 degrees C for 60 days increased the level (per molecule of collagen) of PYD (+98%, P = 0.005), DPD (+42%, P = 0.013), pentosidine (+55-fold, P = 0.005), and the degree of type I collagen C-telopeptide isomerization (+4.9-fold, P = 0.005). These biochemical changes of collagen were associated with a 30% decrease in bending and compressive yield stress and a 2.5-fold increase in compressive post-yield energy absorption (P < 0.02 for all), with no significant change of bone stiffness. In multivariate analyses, the level of collagen cross-linking was associated with yield stress and post-yield energy absorption independently of bone mineral density, explaining up to 25% of their variance. We conclude that the extent and nature of collagen cross-linking contribute to the mechanical properties of fetal bovine cortical bone independently of bone mineral density.

Synthesis of prolyl 4-hydroxylase alpha subunit and type IV collagen in hemocytic granular cells of silkworm, Bombyx mori: Involvement of type IV collagen in self-defense reaction and metamorphosis.

PubMed

Adachi, Takahiro; Tomita, Masahiro; Yoshizato, Katsutoshi

2005-04-01

The present study shows that hemocytic granular cells synthesize and secrete type IV collagen (ColIV) in the silkworm Bombyx mori (B. mori) and suggests that these cells play roles in the formation of basement membrane, the encapsulation of foreign bodies, and the metamorphic remodeling of the gut. The full- and partial-length cDNA of B. mori prolyl 4-hydroxylase alpha subunit (BmP4Halpha) and B. mori ColIV (BmColIV) were cloned, respectively. In situ hybridization and immunocytochemistry on larval tissues and cells identified hemocytic granular cells as the cells that express mRNAs and proteins of both BmP4Halpha and BmColIV. Immunohistochemistry and immunocytochemistry demonstrated that BmColIV was present in the basement membrane and in the secretory granules of granular cells, respectively. Granular cells in culture secreted BmColIV without accompanying the degranulation and discharged it from the granules when the cells were degranulated. Nylon threads were inserted into the hemocoel of larvae. Granular cells concentrated around the nylon threads and encapsulated them as a self-defense reaction. BmColIV was found to be a component of the capsules. Furthermore, the present study showed that actively BmColIV-expressing granular cells accumulated around the midgut epithelium and formed BmColIV-rich thick basal lamina-like structures there in larval to pupal metamorphosis.

Radiolucent cage for cervical vertebral reconstruction: a prospective study of 17 cases with 2-year minimum follow-up.

PubMed

Söderlund, C H; Pointillart, V; Pedram, M; Andrault, G; Vital, J M

2004-12-01

In cervical spondylotic myelopathy, extended anterior spinal cord decompression necessitates subsequent stable vertebral reconstruction. Reconstruction with an iliac crest graft and screw-plate fixation gives satisfactory clinical and radiological results, but they are often compromised by morbidity involving the bone harvest. The purpose of this study was to evaluate the contribution to cervical reconstruction of a biocompatible, radiolucent cage combined with screw-plate fixation, making use of bone harvested in situ. This prospective study was performed between July 2000 and March 2001 in eight women and nine men (mean age, 55 years) operated for cervical spondylotic myelopathy. Situated between levels C3 and C6, the cage was inserted after one corporectomy in ten patients, two corporectomies in five patients, and three corporectomies in two patients. The cage consisted of a polyester mesh impregnated with poly-L-lactic acid (PLLA) conferring temporary rigidity to the cage during bony fusion. Clinical and radiological follow-up (plain films, computed tomographic reconstruction in three cases) was performed at 2 months, 6 months, 12 months, 24 months and 36 months, postoperatively, with a mean follow-up of 30 months. Functional results were evaluated according to the Japanese Orthopaedic Association's scoring system. An independent surgeon assessed the radiological evidence of anterior cervical fusion using the grades proposed by Bridwell [6]. Every patient experienced neurological recovery. At last follow-up, radiological findings were consistent with grade I (complete fusion) in five cases, grade II (probable fusion) in ten cases, grade III (radiolucent halo in favor of non fusion) in one case, and grade IV (graft lysis) in one case with persistent neck pain. In three cases there was screw breakage (two grade II, one grade IV). None of these cases required surgical revision at latest follow-up. In extensive spinal cord decompression through an anterior approach, cervical reconstruction using the present type of cage can achieve clinical results comparable to conventional techniques. The rigidity of the cage meets biomechanical imperatives. Its radiolucency permits one to monitor the course of consolidation, contrary to metal cages. The cases of probable non-fusion and screw breakage were not accompanied by signs of instability on the flexion extension films. This cage meets the biologic and biomechanical imperatives of cervical reconstruction. It obviates complications involving bone harvest.

The Role of Dipeptidyl Peptidase IV in Lung Metastasis of Breast Cancer Cells

DTIC Science & Technology

1999-05-01

Our studies focused on (1) cloning and sequencing of wild-type endothelial DPP IV (wtDPP IV) and preparation of truncated DPP IV ( tDPP IV); (2...that was identical to hepatic DPP IV. Acid extraction of rat lung yielded a tDPP IV, which was an effective inhibitor of breast cancer cell adhesion to

Long-term degradation of a poly-lactide co-glycolide/β-tricalcium phosphate biocomposite interference screw.

PubMed

Barber, F Alan; Dockery, W D; Hrnack, Scott A

2011-05-01

To evaluate the long-term in vivo degradation of biodegradable interference screws made of poly-L-lactide co-glycolide (poly-L-lactic acid [PLLA]/polyglycolic acid [PGA]) and β-tricalcium phosphate (β-TCP). To study in vivo the biological behavior of a PLLA/PGA/β-TCP biocomposite screw (Milagro; DePuy Mitek, Raynham, MA), an institutional review board-approved program using anterior cruciate ligament (ACL) interference fixation screws was initiated in 2005. Thirteen patients who had bone-patellar tendon-bone ACL reconstruction fixed at both the femur and tibia with PLLA/PGA/β-TCP screws at least 24 months earlier were evaluated by physical, radiographic, and computed tomography (CT) evaluations. Lysholm, Tegner, Cincinnati, and International Knee Documentation Committee scores were also obtained. Radiographs and CT scans of the operated knee were obtained. CT scan data measured in Hounsfield units (HU) evaluated the material density at the screw and bone plug sites. Soft-tissue and cancellous and cortical bone site readings were also taken. Osteoconductivity scores were determined at the screw sites by use of an ossification quality score (range, 1 to 4). Eleven men and two women were evaluated at a mean of 38 months after surgery (range, 24 to 49 months). CT scans and radiographs showed the bone plug fused to the tunnel wall with no PLLA/PGA/β-TCP screw remaining. The screws were replaced with material that was calcified and non-trabecular. Osteoconductivity was present in 21 of 26 tunnels (81%) and complete (type 4 ossification) in 5 of 26 (19%). Mean screw site densities (femoral, 159 HU; tibial, 157 HU) were not different from the mean cancellous bone density (femoral, 146 HU; tibial, 140 HU). No positive pivot-shift tests were found. Lysholm, Tegner, and Cincinnati scores improved from 44, 3.7, and 37 preoperatively to 93, 6, and 87 at follow-up, respectively. The mean KT arthrometer (MEDmetric, San Diego, CA) difference was 0.8 mm. The PLLA/PGA/β-TCP interference screw completely degraded, and no remnant was present 3 years after implantation for a bone-patellar tendon-bone graft ACL reconstruction. Osteoconductivity was confirmed in 21 of 26 screw sites (81%) and completely filled the site in 5 of 26 (19%). The PLLA/PGA/β-TCP biocomposite interference screw is osteoconductive. Level IV, therapeutic case series. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Evaluation of stability of osteosynthesis with K-wires on an artificial model of tibial malleolus fracture.

PubMed

Bumči, Igor; Vlahović, Tomislav; Jurić, Filip; Žganjer, Mirko; Miličić, Gordana; Wolf, Hinko; Antabak, Anko

2015-11-01

Paediatric ankle fractures comprise approximately 4% of all paediatric fractures and 30% of all epiphyseal fractures. Integrity of the ankle "mortise", which consists of tibial and fibular malleoli, is significant for stability and function of the ankle joint. Tibial malleolar fractures are classified as SH III or SH IV intra-articular fractures and, in cases where the fragments are displaced, anatomic reposition and fixation is mandatory. Type SH III-IV fractures of the tibial malleolus are usually treated with open reduction and fixation with cannulated screws that are parallel to the physis. Two K-wires are used for temporary stabilisation of fragments during reduction. A third "guide wire" for the screw is then placed parallel with the physis. Considering the rules of mechanics, it is assumed that the two temporary pins with the additional third pin placed parallel to the physis create a strong triangle and thus provide strong fracture fixation. To prove this hypothesis, an experiment was conducted on the artificial models of the lower end of the tibia from the company "Sawbones". Each model had been sawn in a way that imitates the fracture of medial malleoli and then reattached with 1.8mm pins in various combinations. Prepared models were then tested for tensile and pressure forces. The least stable model was that in which the fractured pieces were attached with only two parallel pins. The most stable model comprised three pins, where two crossed pins were inserted in the opposite compact bone and the third pin was inserted through the epiphysis parallel with and below the growth plate. A potential method of choice for fixation of tibial malleolar fractures comprises three K-wires, where two crossed pins are placed in the opposite compact bone and one is parallel with the growth plate. The benefits associated with this method include shorter operating times and avoidance of a second operation for screw removal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unicameral bone cyst: radiographic assessment of venous outflow by cystography as a prognostic index.

PubMed

Ramirez, Ana; Abril, Juan Carlos; Touza, Alberto

2012-11-01

The aim of this study was to determine the benefits of cystography in the management of a simple bone cyst, its implication in the final result of the treatment after corticoid intracystic injections, and the presence of secondary effects. We retrospectively reviewed 42 patients diagnosed with a simple bone cyst. Cystography was performed before the corticoid injection. The presence or absence of loculation intracyst and the existence and number of venous outflows were determined. According to the venous drainage, cysts were classified as type 0 when a venous outflow did not exist and as type 1 when there was a rapid venous outflow (<3 min). The treatment protocol included a maximum of three corticoid injections at an interval of 6 months. Healing of the cyst was determined on the basis of Neer's criteria. Secondary effects and surgical complications were assessed. Cystography studies showed a unicameral bone cyst with absent loculation in 16 cases (37.3%), whereas the lesion showed multiloculation in 26 cases (62.7%). There was no statistical difference between loculation intracyst (present or absent) and the final outcomes of the 42 cysts treated with a steroid injection (P=0.9). Cystography showed a negative venogram in 10 cases (23.8%), whereas the cysts showed a rapid venous outflow in 32 cases (76.2%). On the basis of Neer's classification, all patients with a negative venogram achieved complete healing of the cyst. Patients with a rapid venous outflow achieved complete healing in 14 cases (Neer I). In two patients, the healing was incomplete at the end of the follow-up period (Neer IV). In most cases (21 cysts), healing was partial (Neer II). Five patients showed a recurrence after initial healing of the cyst (Neer III) (P<0.05). The number or the size of veins did not affect healing of a bone cyst (P=0.6). Two patients with a rapid venous outflow showed a generalized hypertrichosis after the first injection of corticosteroids. Sex and age at the initiation of the first injection were not significant factors of healing (P=0.4). The average follow-up time was 59 months (24-60 months). Cystography provides morphological and functional information of simple bone cyst. It is a useful test before the administration of percutaneous injections of sclerosing substances. It facilitates the differentiation of cysts that may achieve complete healing (negative venogram) from those that tend to show recurrence (rapid venous outflow). Therapeutic material should be introduced slowly and a second trocar should always be placed to decrease the risk of migration in cysts with communication with the venous system. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Bone grafts utilized in dentistry: an analysis of patients' preferences.

PubMed

Fernández, Ramón Fuentes; Bucchi, Cristina; Navarro, Pablo; Beltrán, Víctor; Borie, Eduardo

2015-10-20

Many procedures currently require the use of bone grafts to replace or recover bone volume that has been resorbed. However, the patient's opinion and preferences must be taken into account before implementing any treatment. Researchers have focused primarily on assessing the effectiveness of bone grafts rather than on patients' perceptions. Thus, the aim of this study was to explore patients' opinions regarding the different types of bone grafts used in dental treatments. One hundred patients were randomly chosen participated in the study. A standardized survey of 10 questions was used to investigate their opinions regarding the different types of bone grafts used in dental treatments. Descriptive statistics were calculated for the different variables, and absolute frequencies and percentages were used as summary measures. A value of p <0.05 was selected as the threshold for statistical significance. The highest rate of refusal was observed for allografts and xenografts. The grafts with the lowest rates of refusal were autologous grafts (3 %) and alloplastics (2 %). No significant differences were found between the various types of bone grafts in the sociodemographic variables or the refusal/acceptance variable. Similarly, no significant relations were observed between a specific religious affiliation and the acceptance/refusal rates of the various types of graft. Allografts and xenografts elicited the highest refusal rates among the surveyed patients, and autologous bone and alloplastics were the most accepted bone grafts. Moreover, no differences were found in the sociodemographic variables or religious affiliations in terms of the acceptance/refusal rates of the different bone grafts.

Matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in paediatric burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors.

PubMed

Weremijewicz, Artur; Matuszczak, Ewa; Sankiewicz, Anna; Tylicka, Marzena; Komarowska, Marta; Tokarzewicz, Anna; Debek, Wojciech; Gorodkiewicz, Ewa; Hermanowicz, Adam

2018-06-01

The purpose of this study was the determination of matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in the blood plasma of burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors. 31 children scalded by hot water who were managed at the Department of Paediatric Surgery between 2014-2015, after primarily presenting with burns in 4-20% TBSA were included into the study (age 9 months up to 14 years, mean age 2,5+1 years). There were 10 girls and 21 boys. Venous blood samples were drawn 2-6h, and 12-16h after the thermal injury, and on the subsequent days 3, 5 and 7. The matrix metalloproteinase-2, collagen type IV and laminin-5 concentrations were assessed using Surface Plasmon Resonance Imaging by the investigators blinded to the other data. The MMP-2, laminin-5 and collagen type IV concentrations in the blood plasma of patients with burns, were highest 12-16h after thermal injury, the difference was statistically significant. The MMP-2, laminin-5 and collagen type IV concentrations measured 3 days, 5 days and 7 days after the thermal injury, slowly decreased over time, and on the 7th day reached the normal range, when compared with the concentration measured in controls. Current work is the first follow-up study regarding MMP-2 in burns. MMP-2, laminin-5 and collagen type IV levels were elevated early after burn injury in the plasma of studied patients, and were highest 12-16h after the injury. MMP-2, laminin-5 and collagen type IV levels were not proportional to the severity of the burn. We believe in the possibility that the gradual decrease of MMP-2, collagen type IV and laminin-5 concentrations could be connected with the process of healing, but to prove it, more investigation is needed in this area. The SPR imaging biosensor is a good diagnostic tool for determination of MMP-2, laminin-5 and collagen type IV in blood plasma of patients with burns. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Endovascular Treatment of a Carotid Dissecting Pseudoaneurysm in a Patient with Ehlers-Danlos Syndrome Type IV with Fatal Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Siok Ping, E-mail: siokpinglim@yahoo.co.uk; Duddy, Martin J.

2008-01-15

We present a patient with Ehlers-Danlos syndrome type IV (EDS IV) with a carotid dissecting pseudoaneurysm causing severe carotid stenosis. This lesion was treated endovascularly. Unfortunately, the patient died of remote vascular catastrophes (intracranial hemorrhage and abdominal aortic rupture). This unique case illustrates the perils of endovascular treatment of EDS IV patients and the need for preoperative screening for concomitant lesions. It also shows that a dissecting pseudoaneurysm can feasibly be treated with a covered stent and that closure is effective using Angioseal in patients with EDS IV.

Deletion of FoxO1, 3, and 4 in Osteoblast Progenitors Attenuates the Loss of Cancellous Bone Mass in a Mouse Model of Type 1 Diabetes

PubMed Central

Iyer, Srividhya; Han, Li; Ambrogini, Elena; Yavropoulou, Maria; Fowlkes, John; Manolagas, Stavros C; Almeida, Maria

2017-01-01

Type 1 diabetes is associated with osteopenia and increased fragility fractures, attributed to reduced bone formation. However, the molecular mechanisms mediating these effects remain unknown. Insulin promotes osteoblast formation and inhibits the activity of the FoxO transcription factors. FoxOs, on the other hand, inhibit osteoprogenitor proliferation and bone formation. Here, we investigated whether FoxOs play a role in the low bone mass associated with type 1 diabetes, using mice lacking FoxO1, 3, and 4 in osteoprogenitor cells (FoxO1,3,4ΔOsx1-Cre). Streptozotocin-induced diabetes caused a reduction in bone mass and strength in FoxO-intact mice. In contrast, cancellous bone was unaffected in diabetic FoxO1,3,4ΔOsx1-Cre mice. The low bone mass in the FoxO-intact diabetic mice was associated with decreased osteoblast number and bone formation, as well as decreased expression of the anti-osteoclastogenic cytokine osteoprotegerin (OPG) and increased osteoclast number. FoxO deficiency did not alter the effects of diabetes on bone formation; however, it did prevent the decrease in OPG and the increase in osteoclast number. Addition of high glucose to osteoblastic cell cultures decreased OPG mRNA, indicating that hyperglycemia in and of itself contributes to diabetic bone loss. Taken together, these results suggest that FoxOs exacerbate the loss of cancellous bone mass associated with type 1 diabetes and that inactivation of FoxOs might ameliorate the adverse effects of insulin deficiency. PMID:27491024

Experimental study on differences in clivus chordoma bone invasion: an iTRAQ-based quantitative proteomic analysis.

PubMed

Wu, Zhen; Wang, Liang; Guo, Zhengguang; Wang, Ke; Zhang, Yang; Tian, Kaibing; Zhang, Junting; Sun, Wei; Yu, Chunjiang

2015-01-01

Although a bone tumor, significant differences in the extent of bone invasion exist in skull base chordoma, which directly affect the extent of surgical resection, and have an impact on its prognosis. However, the underlying mechanism of the phenomenon is not clearly understood. Therefore, we used an iTRAQ-based quantitative proteomics strategy to identify potential molecular signatures, and to find predictive markers of discrepancy in bone invasion of clivus chordoma. According to bone invasive classification criteria, 35 specimens of clivus chordoma were calssified to be either endophytic type (Type I) or exophytic type (Type II). An initial screening of six specimens of endophytic type and six of exophytic was performed, and 250 differentially expressed proteins were identified. Through the GO and IPA analysis, we found evidence that the expression of inflammatory activity-associated proteins up-regulated in endophytic type, whereas the expression of cell motility-associated proteins up-regulated in exophytic ones. Moreover, TGFβ1 and mTOR signal pathway seemed to be related with bone invasion. Thus, TGFβ1, PI3K, Akt, mTOR, and PTEN were validated in the following 23 samples by immune histochemistry and Western blot. The expression levels of TGFβ1 and PTEN were significantly lower in the endophytic type than in the exophytic ones. It was found that TGFβ1 may play an important role in its bone invasion. The mechanisms may be related with conducting an increased inflammatory cell response and a decline in cytoskeletal protein expression. PTEN is confirmed to be associated with the degree of bone invasion. The PI3K/AKT/mTOR signaling pathway might be associated with the bone invasion, but still needs a larger sample size to be verified These results, for the first time, not only demonstrate the biological changes that occur in different growth patterns from the perspective of proteomics, but also provide novel markers that may help to reveal the mechanisms behind clivus chordomas.

Generalized metabolic bone disease in Neurofibromatosis type I

USDA-ARS?s Scientific Manuscript database

Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats.

PubMed

Lapmanee, Sarawut; Charoenphandhu, Narattaphol; Aeimlapa, Ratchaneevan; Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Kengkoom, Kanchana; Chaimongkolnukul, Khuanjit; Seriwatanachai, Dutmanee; Krishnamra, Nateetip

2014-10-01

Type 2 diabetes mellitus (T2DM) often occurs concurrently with high blood cholesterol or dyslipidemia. Although T2DM has been hypothesized to impair bone microstructure, several investigations showed that, when compared to age-matched healthy individuals, T2DM patients had normal or relatively high bone mineral density (BMD). Since cholesterol and lipids profoundly affect the function of osteoblasts and osteoclasts, it might be cholesterol that obscured the changes in BMD and bone microstructure in T2DM. The present study, therefore, aimed to determine bone elongation, epiphyseal histology, and bone microstructure in non-obese T2DM Goto-Kakizaki rats treated with normal (GK-ND) and high cholesterol diet. We found that volumetric BMD was lower in GK-ND rats than the age-matched wild-type controls. In histomorphometric study of tibial metaphysis, T2DM evidently suppressed osteoblast function as indicated by decreases in osteoblast surface, mineral apposition rate, and bone formation rate in GK-ND rats. Meanwhile, the osteoclast surface and eroded surface were increased in GK-ND rats, thus suggesting an activation of bone resorption. T2DM also impaired bone elongation, presumably by retaining the chondrogenic precursor cells in the epiphyseal resting zone. Interestingly, several bone changes in GK rats (e.g., increased osteoclast surface) disappeared after high cholesterol treatment as compared to wild-type rats fed high cholesterol diet. In conclusion, high cholesterol diet was capable of masking the T2DM-induced osteopenia and changes in several histomorphometric parameters that indicated bone microstructural defect. Cholesterol thus explained, in part, why a decrease in BMD was not observed in T2DM, and hence delayed diagnosis of the T2DM-associated bone disease.

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

PubMed

de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

Characterization of Staphylococcus aureus faecal isolates associated with food-borne disease in Korea.

PubMed

Shin, E; Hong, H; Park, J; Oh, Y; Jung, J; Lee, Y

2016-07-01

To characterize Staphylococcus aureus faecal isolates from people suspected to be infected with food poisoning by using antimicrobial susceptibility testing and molecular techniques. A total of 340 Staph. aureus isolates from 6226 people suspected to be infected with food poisoning were identified and characterized by biochemical methods, antimicrobial susceptibility testing and PCR. Samples were obtained from January 2006 to December 2008 from the National Notifiable Diseases Surveillance System at the Research Institute of Public Health and Environment in Seoul Metropolitan, Korea. All strains carried at least one of the eight staphylococcal enterotoxin (se) genes tested and a total of 27 se profiles were produced; the most frequent se profile was seg-sei and the next was sea. Among the total isolates, 36 methicillin-resistant Staphylococcus aureus (MRSAs) isolates were further analysed by multilocus sequence typing (MLST), Staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE) and PCR detection for pvl. ST72-SCCmec type IV was the most predominant clone (27 isolates, 75%) followed by ST1-SCCmec type IV (five isolates, 13·8%), ST20-SCCmec type IV (one isolate, 2·8%), ST493-SCCmec type IV (one isolate, 2·8%), ST903-SCCmec type IV (one isolate, 2·8%) and ST5-SCCmec type II (one isolate, 2·8%). By PFGE typing, MRSAs isolated during the same period were grouped together although they were isolated from different regions. None of MRSAs had PVL gene and nine MRSAs were multidrug resistant. Analysis of MRSAs by MLST, SCCmec typing, PFGE and pvl detection showed that the majority of strain associated with food-borne diseases belonged to a Korean community-acquired (CA) MRSA clone with ST72-SCCmec type IV-PVL negative-SEG/SEI and its variations while one strain was hospital-acquired (HA) MRSA. CA-MRSA clone which possessed ST72-SCCmec type IV-PVL negative-SEG/SEI was spread most commonly among MRSAs that were associated with food-borne diseases. This is the first report of ST903 strain in Korea. © 2016 The Society for Applied Microbiology.

Adenocarcinoma of the lung with scattered consolidation: radiological-pathological correlation and prognosis.

PubMed

Jiang, Binghu; Takashima, Shodayu; Hakucho, Tomoaki; Hodaka, Numasaki; Yasuhiko, Tomita; Masahiko, Higashiyama

2013-10-01

To investigate the clinicopathological features and prognosis in patients with adenocarcinoma of the lung with scattered consolidation (ALSC). Between January 2006 and March 2010, 139 consecutive patients with lung adenocarcinoma of ≤3 cm, who underwent pulmonary resection for lung cancer, were investigated retrospectively. Radiologic classification was based on the findings of thin-section CT such as the presence of consolidation or ground-glass opacity (GGO). Type I (n=15) and Type II (n=14), showed a pure GGO and a mixed GGO with consolidation <50%, respectively. Type IV (n=38) and Type V (n=52) showed a mixed GGO with consolidation ≥50% and a pure consolidation, respectively. Type III (n=20) was the adenocarcinoma of the lung with scattered consolidation (ALSC). The clinicopathological features and prognosis of ALSC was investigated with comparative analysis and survival analysis. Because of the similar recurrence rate for Type I and Type II (P=1.000), Type IV and Type V (P=0.343), we merged Type I and Type II as Type I+II, Type IV and Type V as Type IV+V, respectively. In the 20 (14.4%) patients with ALSC, lymph node metastasis was not observed, and it was rare in lymphatic invasion and vascular invasion. On the basis of IASLC/ATS/ERS 2011 classification, 80% of the ALSC were preinvasive lesions. In Noguchi classification, there was no significant difference between Type I+II and ALSC (P=0.260). The prognosis of ALSC was similar to Type I+II (P=0.408), but better than Type IV+V (P=0.040). Adenocarcinoma of the lung with scattered consolidation (ALSC) on thin-section CT was a relatively favorable prognostic factor. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

46 CFR 164.019-3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Guard-approved PFDs. Commandant means the Chief of the Lifesaving and Fire Safety Division, Office of... code PFD type acceptable for use 1 I, II, and III. 2 II and III. 3 III. 4B IV (all Ring Buoys). 4BC IV (Buoyant Cushions). 4RB IV (Recreational Ring Buoys only). 5 Wearable Type V (intended use must be...

Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hagspiel, Klaus D., E-mail: kdh2n@virginia.edu; Bonatti, Hugo; Sabri, Saher

2011-04-15

Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.

Secure fixation of femoral bone plug with a suspensory button in anatomical anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft

PubMed Central

TAKETOMI, SHUJI; INUI, HIROSHI; NAKAMURA, KENSUKE; YAMAGAMI, RYOTA; TAHARA, KEITARO; SANADA, TAKAKI; MASUDA, HIRONARI; TANAKA, SAKAE; NAKAGAWA, TAKUMI

2015-01-01

Purpose the efficacy and safety of using a suspensory button for femoral fixation in anatomical anterior cruciate ligament (ACL) reconstruction with bone-patellar tendon-bone (BPTB) graft have not been established. The purpose of the current study was to evaluate bone plug integration onto the femoral socket and migration of the bone plug and the EndoButton (EB) (Smith & Nephew, Andover, MA, USA) after rectangular tunnel ACL reconstruction with BPTB autograft. Methods thirty-four patients who underwent anatomical rectangular ACL reconstruction with BPTB graft using EB for femoral fixation and in whom three-dimensional (3D) computed tomography (CT) was performed one week and one year after surgery were included in this study. Bone plug integration onto the femoral socket, bone plug migration, soft tissue interposition, EB migration and EB rotation were evaluated on 3D CT. The clinical outcome was also assessed and correlated with the imaging outcomes. Results the bone plug was integrated onto the femoral socket in all cases. The incidence of bone plug migration, soft tissue interposition, EB migration and EB rotation was 15, 15, 9 and 56%, respectively. No significant association was observed between the imaging outcomes. The postoperative mean Lysholm score was 97.1 ± 5.0 points. The postoperative side-to-side difference, evaluated using a KT-2000 arthrometer, averaged 0.5 ± 1.3 mm. There were no complications associated with EB use. Imaging outcomes did not affect the postoperative KT side-to-side difference. Conclusions the EB is considered a reliable device for femoral fixation in anatomical rectangular tunnel ACL reconstruction with BPTB autograft. Level of evidence Level IV, therapeutic case series. PMID:26889465

Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: a Raman spectroscopic study.

PubMed

Pinheiro, Antonio L B; Aciole, Gilberth T S; Cangussú, Maria Cristina T; Pacheco, Marcos T T; Silveira, Landulfo

2010-12-15

We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p < 0.001), but not with Group X (p = 0.09). At day 21 differences were seen between all groups (p = 0.031) and between Groups VIII and X when compared with Groups VI (p = 0.03), V (p < 0.001), IV (p < 0.001), and IX (p = 0.04). At the end of the experimental period no significant differences were seen. On regards CH, significant differences were seen at the 15(th) day (p = 0.002) and between Group II and all other groups (p < 0.0001) but not with control. Advanced maturation on irradiated bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. Copyright © 2010 Wiley Periodicals, Inc.

Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency

ClinicalTrials.gov

2018-02-20

ATM Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Homologous Recombination Deficiency; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Bone Cancer

MedlinePlus

Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

Interstellar C IV and Si IV column densities toward early-type stars

NASA Technical Reports Server (NTRS)

Bruhweiler, F. C.; Kondo, Y.; Mccluskey, G. E.

1980-01-01

Equivalent widths and deduced column densities of Si IV and C IV are examined for 18 early-type close binaries, and physical processes responsible for the origin of these ions in the interstellar medium are investigated. The available C IV/Si IV column density ratios typically lie within a narrow range from 0.8 to 4.5, and there is evidence that the column density of C IV is higher than that of N V along most lines of sight, suggesting that C IV is not formed in the same hot region as O VI. In addition, the existence of regions with a narrowly defined new temperature range around 50,000 deg K is indicated. The detection of the semitorrid gas of Bruhweiler, Kondo, and McCluskey (1978, 1979) is substantiated, and the relation of this gas to the observations of coronal gas in the galactic halo is discussed.

Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway

PubMed Central

Li, Na; Zhang, Min; Drummen, Gregor P. C.; Zhao, Yu; Tan, Yin Fen; Luo, Su; Qu, Xiao Bo

2016-01-01

Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone injury and/or in scaffolds for bone replacement strategies. Finally, isolation of SDA-Col I from deer antler represents a renewable, green, and uncomplicated way to obtain a biomedically valuable therapeutic. PMID:27066099

Interpretation and classification of bone scintigraphic findings in stress fractures.

PubMed

Zwas, S T; Elkanovitch, R; Frank, G

1987-04-01

A new system for classification of stress fractures identified by bone scintigraphy was developed and divided into four grades according to lesion dimension, bone extension, and tracer accumulation. The scintigraphic findings were evaluated for severity of lesions by extent of the visualized bone response, ranging from ill-defined cortical lesions with slightly increased activity (I) to well-defined intramedullary transcortical lesions with intensely increased activity (IV). Bone scintigraphies using [99mTc]MDP were obtained in 310 military recruits suspected of having stress fractures. In 235 patients, 391 stress fractures were diagnosed. Forty percent of the lesions were asymptomatic. Most of the lesions were in the tibiae (72%), and 87% of the patients had one or two lesions, while 13% had three to five lesions. Eighty-five percent of the lesions were classified as mild and showed early and more complete resolution on follow-up studies after treatment as compared to the severe grades. Furthermore, specific scintigraphic patterns have been introduced for distinguishing inflammatory shin-splints from stress fractures, allowing for their appropriate early treatment. Thus, early recognition of mild stress fracture scintigraphic patterns representing the beginning of pathologic bone response to stress enabled a prompt and effective treatment to prevent progression of lesions, protracted disability, and complications.

One-stage metatarsal lengthening by allograft interposition: a novel approach for congenital brachymetatarsia.

PubMed

Giannini, Sandro; Faldini, Cesare; Pagkrati, Stavroula; Miscione, Maria Teresa; Luciani, Deianira

2010-07-01

Congenital brachymetatarsia, a shortened metatarsal bone, can be corrected surgically by callus distraction or one-stage lengthening using bone graft. We asked whether one-stage metatarsal lengthening using metatarsal homologous bone graft could improve forefoot function, lead to metatarsal healing, restore metatarsal parabola, and improve cosmetic appearance. We retrospectively reviewed 29 patients (41 feet) in whom we lengthened 50 metatarsals. Surgery consisted of a transverse proximal osteotomy of the metatarsal shaft and interposition of a metatarsal homologous bone graft (average, 13 mm long) fixed with an intramedullary Kirschner wire. Minimum followup was 3 years (mean, 5 years; range, 3-11 years). Bone union was achieved in all cases. The mean preoperative American Orthopaedic Foot and Ankle Society score was 37 points (range, 28-53 points) and the mean postoperative score was 88 points (range, 74-96 points), with an average improvement of 51 points. Radiographically, the mean gain in length was 13 mm (range, 10-15 mm), and the mean percentage increase was 23%. One-stage metatarsal lengthening using interposition of metatarsal homologous bone graft to correct congenital brachymetatarsia has low morbidity for the patient, limited complications, short recovery times, and restores forefoot anatomy. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

TCDD disrupts posterior palatogenesis and causes cleft palate.

PubMed

Yamada, Tomohiro; Hirata, Azumi; Sasabe, Eri; Yoshimura, Tomohide; Ohno, Seiji; Kitamura, Naoya; Yamamoto, Tetsuya

2014-01-01

Dioxins (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) cause cleft palate at a high rate. A post-fusional split may contribute to the pathogenesis, and tissue fragility may be a concern. The objective of this study was to investigate the effects of TCDD on the palatal epithelium, bone and muscle, which contribute to tissue integrity. ICR mice (10-12 weeks old) were used. TCDD was administered on E12.5 at 40 mg/kg. Immunohistochemical staining for AhR, ER-α, laminin, collagen IV, osteopontin, Runx2, MyoD, and desmin were performed. Furthermore, western blot analysis for osteopontin, Runx2, MyoD, and desmin were performed to evaluate protein expression in the palatal tissue. Immunohistologically, there was little difference in the collagen IV and laminin localization in the palatal epithelium between control versus TCDD-treated mice. Runx2 and osteopontin immunoreactivity decreased in the TCDD-treated palatal bone, and MyoD and desmin decreased in the TCDD-treated palatal muscle. AhR and ER-α immunoreactivity were localized to the normal palatal bone, but ER-α was diminished in the TCDD-treated palate. On western blot analysis, Runx2, MyoD, and desmin were all downregulated in the TCDD-treated palate. TCDD may suppress palatal osteogenesis and myogenesis via AhR, and cause cleft palates via a post-fusional split mechanism, in addition to a failure of palatal fusion. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Regulation of DMT1 on Bone Microstructure in Type 2 Diabetes

PubMed Central

Zhang, Wei-Lin; Meng, Hong-Zheng; Yang, Mao-Wei

2015-01-01

Diabetic osteoporosis is gradually attracted people's attention. However, the process of bone microstructure changes in diabetic patients, and the exact mechanism of osteoblast iron overload are unclear. Therefore, the present study aimed to explore the function of DMT1 in the pathological process of diabetic osteoporosis. We build the type two diabetes osteoporosis models with SD rats and Belgrade rats, respectively. Difference expression of DMT1 was detected by using the method of immunohistochemistry and western blotting. Detection of bone microstructure and biomechanics and iron content for each group of samples. We found that DMT1 expression in type 2 diabetic rats was higher than that in normal rats. The bone biomechanical indices and bone microstructure in the rat model deficient in DMT1 was significantly better than that in the normal diabetic model. The loss of DMT1 can reduce the content of iron in bone. These findings indicate that DMT1 expression was enhanced in the bone tissue of type 2 diabetic rats, and plays an important role in the pathological process of diabetic osteoporosis. Moreover, DMT1 may be a potential therapeutic target for diabetic osteoporosis. PMID:26078704

Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls.

PubMed

Pritchard, Janet M; Giangregorio, Lora M; Atkinson, Stephanie A; Beattie, Karen A; Inglis, Dean; Ioannidis, George; Punthakee, Zubin; Adachi, J D; Papaioannou, Alexandra

2012-01-01

Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM. An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 μm(3) voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x-ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up-and-go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI). Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups. In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population. Copyright © 2012 by the American College of Rheumatology.

Luminol testing in detecting modern human skeletal remains: a test on different types of bone tissue and a caveat for PMI interpretation.

PubMed

Caudullo, Giorgio; Caruso, Valentina; Cappella, Annalisa; Sguazza, Emanuela; Mazzarelli, Debora; Amadasi, Alberto; Cattaneo, Cristina

2017-01-01

When forensic pathologists and anthropologists have to deal with the evaluation of the post-mortem interval (PMI) in skeletal remains, luminol testing is frequently performed as a preliminary screening method. However, the repeatability of this test on the same bone, as well as comparative studies on different bones of the same individual, has never been performed. Therefore, with the aim of investigating the influence that different types of bones may exert on the response to the luminol test, the present study analysed three different skeletal elements (femoral diaphysis, vertebra and cranial vault), gathered from ten recent exhumed skeletons (all with a 20-year PMI). The analysis was performed twice on the same bone after 2 months: the analysis at time 0 concerned the whole bone, whereas the second concerned only a part of the same bone taken during the first test (which already had been broken). The overall results showed different responses, depending on the type of bone and on the integrity of the samples. Negative results at the first analysis (6.6% out of the total of samples) are consistent with what is reported in the literature, whilst at the second analysis, the increase of about 20% of false-negative results highlights that the luminol test ought to be performed with caution in case of broken bones or elements which are taphonomically altered. Results have thus proven that the exposition to environmental agents might result in haemoglobin (Hb) loss, as detected even after only 2 months. The study also focused on the crucial issue of the type of bone subjected to testing, remarking the suitability of the femoral diaphysis (100% of positive responses at the first analysis vs only 18% of false-negative results at the second test, corresponding to 5% of total false-negative results) as opposed to other bone elements that showed a low yield. In particular, the cranial vault gave poor results, with 40% of discrepancy between results from the two analyses, which suggests caution in choosing the type of bone sample to test. In conclusion, luminol testing should be used with caution on bones different from long bones or on non-intact bones.

Serotype IV and invasive group B Streptococcus disease in neonates, Minnesota, USA, 2000-2010.

PubMed

Ferrieri, Patricia; Lynfield, Ruth; Creti, Roberta; Flores, Aurea E

2013-04-01

Group B Streptococcus (GBS) is a major cause of invasive disease in neonates in the United States. Surveillance of invasive GBS disease in Minnesota, USA, during 2000-2010 yielded 449 isolates from 449 infants; 257 had early-onset (EO) disease (by age 6 days) and 192 late-onset (LO) disease (180 at age 7-89 days, 12 at age 90-180 days). Isolates were characterized by capsular polysaccharide serotype and surface-protein profile; types III and Ia predominated. However, because previously uncommon serotype IV constitutes 5/31 EO isolates in 2010, twelve type IV isolates collected during 2000-2010 were studied further. By pulsed-field gel electrophoresis, they were classified into 3 profiles; by multilocus sequence typing, representative isolates included new sequence type 468. Resistance to clindamycin or erythromycin was detected in 4/5 serotype IV isolates. Emergence of serotype IV GBS in Minnesota highlights the need for serotype prevalence monitoring to detect trends that could affect prevention strategies.

Bone Graft Alternatives

MedlinePlus

... Spine Treatment Spondylolisthesis BLOG FIND A SPECIALIST Treatments Bone Graft Alternatives Patient Education Committee Patient Education Committee ... procedure such as spinal fusion. What Types of Bone Grafts are There? Bone grafts that are transplanted ...

A comparison of bone-related biomarkers and CA27.29 to assess response to treatment of osseous metastatic breast cancer.

PubMed

Lüfter, D; Richter, A; Günther, S; Flath, B; Akrivakis, C; Geppert, R; Wernecke, K D; Possinger, K

2000-01-01

The assessment of bone metastases by clinical examination or imaging techniques is still considered unreliable. We compared a specific marker of bone resorption, urinary deoxypyridinoline (DPD)-crosslinks, with serum calcium (Ca), alkaline phosphatase (AP) and CA27.29, to evaluate the status of bone metastases in patients with breast cancer. Second morning voided urine was collected from 2 groups of patient (pts), those without evidence of disease (n = 118), and those with bone metastases (n = 85) under specific therapy plus pamidronate. DPD and CA27.29 were measured on the automated ACS180 system (Bayer Diagnostics, Tarrytown, NY, USA). Receiver operating characteristics (ROC) curves were established for each of the 4 biomarkers to determine whether they could distinguish the 2 subsets of pts with clinically sufficient validity, and to establish the corresponding cut-off values. Neither Ca nor AP was useful in discriminating the 2 subgroups. At a DPD cut-off of 13 nmol/mmol, we found a specificity of 69% and a sensitivity of 53% for diagnosing bone metastases. Best results, however, were seen for CA27.29. A cut-off value of 30 U/ml resulted in a specificity of 62% and a sensitivity of 81%. CA27.29 was the best parameter for the discrimination of stage IV breast cancer with bone metastases. The primary advantage of DPD lies in the monitoring of bone metastases under specific therapy.

The effects of wearing Passenger Protective Breathing Equipment on evacuation times through type III and type IV emergency aircraft exits in clear air and smoke.

DOT National Transportation Integrated Search

1989-11-01

The effects of Passenger Protective Breathing Equipment (PPBE) on the time required for simulated emergency evacuations through Type III and Type IV overwing aircraft exits were studied in two quasi-independent experiments, one in clear air and anoth...

Investigation of composition and structure of spongy and hard bone tissue using FTIR spectroscopy, XRD and SEM

NASA Astrophysics Data System (ADS)

Al-Akhras, M.-Ali H.; Hasan Qaseer, M. K.; Albiss, B. A.; Alebrhim, M. Anwar; Gezawa, Umar S.

2018-02-01

Valuable structural and chemical features can be obtained for spongy and hard bone by infrared spectroscopy and X-ray diffraction. A better understanding of chemical and structural differences between spongy and hard bone is a very important contributor to bone quality. Our data according to IR data showed that the collagen cross-links occurred to be higher in spongy bone, and crystallinity was lower in spongy bone. Deconvolution of the infrared band near 870 cm-1 reveals evidence for A2-type carbonate substitution on hydroxyapatite of spongy bone in addition to the A and B type carbonate substitution that are also found in hard bone. IR and XRD data confirmed the results of each other since full width at half maximum of 002-apatite pattern of XRD showed that the crystallinity was lower in spongy bone. The microstructure was examined by using scanning electron microscope and the result showed that the lattice of thin threads in spongy bone and is less dense than hard bone.

Kinetic characterization of the deproteinization of trabecular and cortical bovine femur bones.

PubMed

Castro-Ceseña, Ana B; Sánchez-Saavedra, M Pilar; Novitskaya, Ekaterina E; Chen, Po-Yu; Hirata, Gustavo A; McKittrick, Joanna

2013-12-01

The present study proposes an interpretation of the mechanism of bone deproteinization. Cortical and trabecular bovine femur bones were deproteinized using 6% NaOCl (37, 50, 60°C). The kinetic parameters (rate constant and activation energy) were calculated, and the surface area of each type of bone was considered. A statistical analysis of the rate constants shows that cortical bone deproteinizes at a lower rate than trabecular. The activation energy is higher for trabecular than cortical bone, and no significant differences are found in the protein concentration values for both bones. Therefore, although trabecular bone deproteinizes at a higher rate than cortical, trabecular bone requires more energy for the deproteinization reaction to take place. Considering that both types of bones are constituted by mineral, protein, and water; the present work shows that the individual inner matrix architecture of trabecular and cortical bones, along with characteristics such as the mineral concentration and its bonding with collagen fibers, may be the responsible factors that control protein depletion. © 2013.

Promising Mid-term Results With a Cup-cage Construct for Large Acetabular Defects and Pelvic Discontinuity.

PubMed

Amenabar, Tomas; Rahman, Wael A; Hetaimish, Bandar M; Kuzyk, Paul R; Safir, Oleg A; Gross, Allan E

2016-02-01

Restoring normal anatomy and achieving stable fixation of the acetabular component can be especially challenging when the surgeon must deal with severe acetabular defects and/or pelvic discontinuity. The cup-cage (CC) construct, where an ilioischial cage is cemented within a biologically fixed porous metal cup, has emerged as an excellent option to treat such challenges. We sought to determine (1) mid-term Kaplan-Meier survival; (2) clinical outcomes based on Merle d'Aubigné-Postel scores; (3) radiological outcomes based primarily on construct migration; and (4) the complication rate for a series of 67 CC procedures performed at our institution. All hip revision procedures between January 2003 and March 2012 where a CC was used (with the exception of tumor cases or acute fracture; four total cases) that had a minimum 2-year followup and that had been seen within the last 2 years were included in this retrospective review. Acetabular bone loss and presence of pelvic discontinuity were assessed according to the Gross classification. Sixty-seven CC procedures with an average followup of 74 months (range, 24-135 months; SD, 34.3) months were identified; 26 of 67 (39%) were Gross Type IV and 41 of 67 (61%) were Gross Type V (pelvic discontinuity). Postoperative clinical and radiological evaluation was done annually. Merle d'Aubigné-Postel scores were recorded and all radiographs were compared with the 6-week postoperative radiographs to evaluate for radiographic loosening or migration. Failure was defined as revision surgery for any cause, including infection. The 5-year Kaplan-Meier survival rate with revision for any cause representing failure was 93% (95% confidence interval [CI], 83.1-97.4), and the 10-year survival rate was 85% (95% CI, 67.2-93.8). The Merle d'Aubigné-Postel score improved significantly from a mean of 6 preoperatively to 13 postoperatively (p < 0.001). Four CC had nonprogressive radiological migration of the ischial flange and they remain stable. We believe that the CC construct is a suitable choice to treat chronic pelvic discontinuity; it also remains a reliable option for the treatment of severe acetabular bone defects if stable fixation cannot be obtained through the use of a trabecular metal cup with or without augments. Level IV, therapeutic study.

An Analysis of Type IV Precision Measurement Equipment Laboratory Logistical Support Relative to the Implementation of F-15/F-16 Two-Level Maintenance

DTIC Science & Technology

1994-09-01

wife, Margie, for her patience and understanding. Graduate school definitely affects the family . Margie allowed me to use many valuable family hours...Consolidations and reorganizations, in which the face of logistics is changing day -by- day , are taking place throughout the Department of Defense. Two...will focus on Type IV F-15 and Type IV F-16 PMELs. Imporane of Research The two-level maintenance concept significantly alters the structure of

The role of disodium pamidronate in the management of bone pain due to malignancy.

PubMed

Groff, L; Zecca, E; De Conno, F; Brunelli, C; Boffi, R; Panzeri, C; Cazzaniga, M; Ripamonti, C

2001-07-01

A number of controlled studies have recently demonstrated the role of disodium pamidronate in the prevention of skeletal complications in patients with metastatic bone disease due to breast cancer and multiple myeloma. They have also shown that it relieves pain and is well tolerated. The aim of this open prospective study was to evaluate the acceptability of a new schedule of pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky Performance Status (KPS) in patients with metastatic bone pain treated with pamidronate in association or not with chemotherapy, radiotherapy, and hormone therapy. Patients with different types of cancer and at least one painful bone metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate weekly for three consecutive doses, with a 3-week interval between the two cycles (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total of 24 infusions. Two hundred patients were enrolled in the study, of whom 94 received at least the first six infusions; 25 patients received all 24 infusions. Pamidronate was well tolerated in the majority of the patients both during the first six infusions and during the whole study period. In the patients under study, pain intensity decreased compared with T0 after the first two infusions (second week of treatment). The mean equivalent daily dose of oral morphine required ranged from 21.5 to 41.5 mg/day and was low and stable during the study. For the patients who remained in the study, the KPS remained around 70 during the whole treatment period and intrasubject analysis showed a substantial stability of the KPS within each subject. A first fracture occurred within 321 days in 25% of the whole population under study. Pamidronate represents a further valid therapy to add to an already consolidated list of therapies such as radiotherapy, chemotherapy, hormone therapy and orthopaedic intervention in the pain management of patients with bone metastases. Future studies are necessary to evaluate the role of pamidronate and the appropriate schedule in patients with advanced or terminal cancer who are no longer being treated with oncological therapies.

Jaw osteonecrosis related to bisphosphonate therapy: a severe secondary disorder.

PubMed

Dannemann, C; Grätz, K W; Riener, M O; Zwahlen, R A

2007-04-01

Bisphosphonate-related osteonecrosis of the jaws (BON), first described in 2003, is gaining importance due to the increasing indication spectrum of bisphosphonate therapy [S. Takeyama, M. Ito, H. Shinoda, A novel bisphosphonate, TRK-530, for periodontitis, Bone 38 (2006) 31-31; M. Tagil, A. W-Dahl, J. Astrand, D. Little, S. Toksvig-Larsen, Decreasing the catabolic response by a single bisphosphonate infusion shortens the healing time in hemicallotasis operations, Bone 38 (2006) 84-85; E. Rodriguez, M.C. Duran, L.M. Rodriguez, R. Ros, M.R. Aleman, M. Rodriguez-Gaspar, A.M. Lopez, E. Garcia-Valdecasas, F. Santolaria, Intravenous (IV) bisphosphonates for osteopenic cancer survivor women: an alternative treatment, Bone 38 (2006) 72-73; D.G. Little, K. Ward, P. Kiely, M.C. Bellemore, J. Briody, C.T. Cowell, Bisphosphonate rescue in distraction osteogenesis: a case series, Bone 38 (2006) 80-80; R. Marx, Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic, J. Oral Maxillofac. Surg. 61 (2003) 1115-1118]. BON patients suffering from varying bony defects and symptoms are extremely restricted in their quality of life. Due to a limited knowledge of the aetiology of BON efficient evidence-based treatment strategies are lacking. Until now 23 patients with bisphosphonate-related osteonecrosis have been admitted to the Department of Cranio-Maxillofacial Surgery of the University of Zurich. A complete history has been recorded. All patients underwent clinical and radiographic examination. CT scans and MRI have been performed in selected cases. All patients had in common that, before signs of BON were observed, a local traumatic incidence had occurred. All patients showed signs of infection which could be remarkably reduced by antibacterial treatment. Furthermore, the period of bisphosphonate treatment was found to be one of the significant factors causing bisphosphonate-related osteonecrosis of the jaws. The aetiology of BON appears to depend on multiple factors: period and type of bisphosphonate therapy and trauma paving the way for an invasion of pathogens. Because evidence based therapy protocols for complete remodelling of bone defect are still missing, prevention in bisphosphonate-treated patients seems to be of utmost importance. A close interdisciplinary collaboration is required.

Collagen IV Diseases: A Focus on the Glomerular Basement Membrane in Alport Syndrome

PubMed Central

Cosgrove, Dominic; Liu, Shiguang

2016-01-01

Alport syndrome is the result of mutations in any of three type IV collagen genes, COL4A3, COL4A4, or COL4A5. Because the three collagen chains form heterotrimers, there is an absence of all three proteins in the basement membranes where they are expressed. In the glomerulus, the mature glomerular basement membrane type IV collagen network, normally comprised of two separate networks, α3(IV)/α4(IV)/α5(IV) and α1(IV)/α2(IV), is comprised entirely of collagen α1(IV)/α2. This review addresses the current state of our knowledge regarding the consequence of this change in basement membrane composition, including both the direct, via collagen receptor binding, and indirect, regarding influences on glomerular biomechanics. The state of our current understanding regarding mechanisms of glomerular disease initiation and progression will be examined, as will the current state of the art regarding emergent therapeutic approaches to slow or arrest glomerular disease in Alport patients. PMID:27576055

Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets.

PubMed

Sá, M A; Andrade, V B; Mendes, R M; Caliari, M V; Ladeira, L O; Silva, E E; Silva, G A B; Corrêa-Júnior, J D; Ferreira, A J

2013-07-01

We evaluated the effects of sodium hyaluronate (HY) and carbon nanotubes functionalized with HY (HY-CNT) on bone repair in the tooth sockets of diabetic rats. Diabetes was induced by streptozotocin (50 mg kg(-1) i.v.), and the sockets were divided into normal control, diabetic control, diabetic treated with HY (1%), and diabetic treated with HY-CNT (100 μg ml(-1)) groups. The sockets were analyzed according to the percentage of bone formation and the number of cell nuclei. The percentage of bone trabeculae was lower in diabetic control animals (11.16 ± 5.10% vs 41.92 ± 6.34% in normal animals) after 14 days. Treating diabetic animals with HY or HY-CNT significantly increased the percentage of neoformed trabeculae (HY: 29.43 ± 3.29%; HY-CNT: 36.90 ± 3.07%). Moreover, the sockets of diabetic animals had an increased number of cell nuclei and HY or HY-CNT reduced this parameter. Our results indicate that HY and HY-CNT restore bone repair in the tooth sockets of diabetic rats, suggesting that these biomaterials are potential adjuvant therapies for the management of diabetes. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.

PubMed

Masuda, Yukinari; Yamanaka, Nobuaki; Ishikawa, Arimi; Kataoka, Mitue; Arai, Takashi; Wakamatsu, Kyoko; Kuwahara, Naomi; Nagahama, Kiyotaka; Ichikawa, Kaori; Shimizu, Akira

2015-06-01

The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis. We examined the alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 ± 17.6 years old) using double immunostaining for the α2(IV) and α5(IV) chains of type IV collagen, and examining the ultrastructural alterations by transmission electron microscopy (TEM) and low-vacuum scanning electron microscopy (LV-SEM). The GBM of IgA nephropathy cases showed various morphological and qualitative alterations. In the TEM findings, thinning, gaps, rupture, thickening with a lamellar and reticular structure and double contours were detected in the GBM. Double immunostaining for α5(IV) and α2(IV) showed thickening of the GBM with reduced α5(IV) and increased α2(IV), or mosaic images of α5(IV) and α2(IV), and holes, fractures, spiny projections and rupture of α5(IV) in the GBM. In addition, LV-SEM showed an etched image and multiple holes in a widening and wavy GBM. These findings might be associated with the development of a brittle GBM in IgA nephropathy. Glomerular basement membrane alterations were frequently noted in IgA nephropathy, and were easily evaluated by double immunostaining for α2(IV) and α5(IV) of type IV collagen and LV-SEM. The application of these analyses to human renal biopsy specimens may enhance our understanding of the alterations of the GBM that occur in human glomerular diseases.

Genetics Home Reference: glycogen storage disease type IV

MedlinePlus

... 000 to 800,000 individuals worldwide. Type IV accounts for roughly 3 percent of all cases of glycogen storage disease. Related Information What information about a genetic condition can statistics ...

Bone and fat connection in aging bone.

PubMed

Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

Evaluation of different rotary devices on bone repair in rabbits.

PubMed

Ribeiro Junior, Paulo Domingos; Barleto, Christiane Vespasiano; Ribeiro, Daniel Araki; Matsumoto, Mariza Akemi

2007-01-01

In oral surgery, the quality of bone repair may be influenced by several factors that can increase the morbidity of the procedure. The type of equipment used for ostectomy can directly affect bone healing. The aim of this study was to evaluate bone repair of mandible bone defects prepared in rabbits using three different rotary devices. Fifteen New Zealand rabbits were randomly assigned to 3 groups (n=5) according to type of rotary device used to create bone defects: I--pneumatic low-speed rotation engine, II--pneumatic high-speed rotation engine, and III--electric low-speed rotation engine. The anatomic pieces were surgically obtained after 2, 7 and 30 days and submitted to histological and morphometric analysis. The morphometric results were expressed as the total area of bone remodeling matrix using an image analysis system. Increases in the bone remodeling matrix were noticed with time along the course of the experiment. No statistically significant differences (p>0.05) were observed among the groups at the three sacrificing time points considering the total area of bone mineralized matrix, although the histological analysis showed a slightly advanced bone repair in group III compared to the other two groups. The findings of the present study suggest that the type of rotary device used in oral and maxillofacial surgery does not interfere with the bone repair process.

Aberrant Bone Density in Aging Mice Lacking the Adenosine Transporter ENT1

PubMed Central

Hinton, David J.; McGee-Lawrence, Meghan E.; Lee, Moonnoh R.; Kwong, Hoi K.; Westendorf, Jennifer J.; Choi, Doo-Sup

2014-01-01

Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density. PMID:24586402

Type 4 pili are dispensable for biofilm development in the cyanobacterium Synechococcus elongatus.

PubMed

Nagar, Elad; Zilberman, Shaul; Sendersky, Eleonora; Simkovsky, Ryan; Shimoni, Eyal; Gershtein, Diana; Herzberg, Moshe; Golden, Susan S; Schwarz, Rakefet

2017-07-01

The hair-like cell appendages denoted as type IV pili are crucial for biofilm formation in diverse eubacteria. The protein complex responsible for type IV pilus assembly is homologous with the type II protein secretion complex. In the cyanobacterium Synechococcus elongatus PCC 7942, the gene Synpcc7942_2071 encodes an ATPase homologue of type II/type IV systems. Here, we report that inactivation of Synpcc7942_2071 strongly affected the suite of proteins present in the extracellular milieu (exo-proteome) and eliminated pili observable by electron microscopy. These results support a role for this gene product in protein secretion as well as in pili formation. As we previously reported, inactivation of Synpcc7942_2071 enables biofilm formation and suppresses the planktonic growth of S. elongatus. Thus, pili are dispensable for biofilm development in this cyanobacterium, in contrast to their biofilm-promoting function in type IV pili-producing heterotrophic bacteria. Nevertheless, pili removal is not required for biofilm formation as evident by a piliated mutant of S. elongatus that develops biofilms. We show that adhesion and timing of biofilm development differ between the piliated and non-piliated strains. The study demonstrates key differences in the process of biofilm formation between cyanobacteria and well-studied type IV pili-producing heterotrophic bacteria. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

10 CFR Appendix IV to Part 960 - Types of Information for the Nomination of Sites as Suitable for Characterization

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Types of Information for the Nomination of Sites as Suitable for Characterization IV Appendix IV to Part 960 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR..., diapirism, tilting, subsidence, faulting, and volcanism. • Estimate of the geothermal gradient. • Estimate...

[Application of bone flap pedicled on retrograde branch of radial artery for treatment of old scaphoid bone fractures of type AO-B].

PubMed

Sun, Qing-peng

2015-05-01

To investigate application of the bone flap pedicled on the retrograde branch of radial artery for treatment of old scaphoid bone fractures of type AO-B. From October 2007 to October 2011,41 patients with old scaphoid bone fractures of type AO-B were treated by transplantation of the bone flap pedicled on the retrograde branch of radial artery including 26 males and 15 females with an average of (27.3±4.5) years old ranging from 16 to 43 years old. The courses before operation ranged from 6 to 22 months with an average of 11 months. All fractures belonged to the type B of AO classification, that is old wrist fracture of scaphoid bone. All patients' wrist function (pain, function, motion, grip strength) were evaluated by Cooney's modifiedwrist scoring system before and 6 months after operation,and the conditions of bone healing were observed during the follow-up time. Among them, 36 patients were followed up from 4 to 15 months with an average of 8.3 months. The wounds were healed well without other complications as infection appearing. X-rays or CT confirmed that all fractures were healed completely. The Cooney wrist score was improved from preoperative 53.61±13.97 to postoperative 81.81±8.71 (P<0.01). The operation of transplantation of the bone flap pedicled on the retrograde branch of radial artery is an effective method to treat old scaphoid bone fractures,which is scientific and has curative effects, and valuable for clinical application.

A Comparison of More and Less Aggressive Bone Debridement Protocols for the Treatment of Open Supracondylar Femur Fractures

PubMed Central

Ricci, William M.; Collinge, Cory; Streubel, Philipp N.; McAndrew, Christopher M.; Gardner, Michael J.

2014-01-01

Objectives This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high energy open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Design Retrospective review Setting Level I and Level II Trauma Centers Patients/Participants Twenty-nine consecutive patients with high grade open (Gustilo Types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Intervention Surgeons at two different Level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a More Aggressive (MA)protocol in their patients (n=17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a Less Aggressive (LA) protocol in their patients (n=12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the two centers were similar: definitive fixation with locked plates in all cases; IV antibiotics were used until definitive wound closure; and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Main Outcome Measurements Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Results Demographics were similar between included patients at each center with regard to: age; gender; rate of open fractures; open fracture classification; mechanism; and smoking (p>.05). Patients at the MA center were more often diabetic (p<.05).Cement spacers to fill segmental defects were used more often after MA debridement (35% vs 0%, p<0.006) and more patients had a plan for staged bone grafting after MA debridement (71% vs 8%, p<0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs 35%, p<0.003). There was no difference in infection rate between the two protocols: 25% with the LA protocol; and 18% with the MA protocol, (p=0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. Conclusion The degree to which bone should be debrided after a high energy, high grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic tradeoff between infection risk and osseous healing potential, seems to favor a less aggressive approach towards bone debridement in the initial treatment. PMID:23760177

A comparison of more and less aggressive bone debridement protocols for the treatment of open supracondylar femur fractures.

PubMed

Ricci, William M; Collinge, Cory; Streubel, Philipp N; McAndrew, Christopher M; Gardner, Michael J

2013-12-01

This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high-energy, open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Retrospective review. Level I and level II trauma centers. Twenty-nine consecutive patients with high-grade, open (Gustilo types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Surgeons at 2 different level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a more aggressive (MA) protocol in their patients (n = 17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a less aggressive (LA) protocol in their patients (n = 12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the 2 centers were similar: definitive fixation with locked plates in all cases, IV antibiotics were used until definitive wound closure, and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Demographics were similar between included patients at each center with regard to age, gender, rate of open fractures, open fracture classification, mechanism, and smoking (P > 0.05). Patients at the MA center were more often diabetic (P < 0.05). Cement spacers to fill segmental defects were used more often after MA debridement (35% vs. 0%, P < 0.006), and more patients had a plan for staged bone grafting after MA debridement (71% vs. 8%, P < 0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs. 35%, P < 0.003). There was no difference in infection rate between the 2 protocols: 25% with the LA protocol and 18% with the MA protocol (P = 0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. The degree to which bone should be debrided after a high-energy, high-grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic trade-off between infection risk and osseous healing potential seems to favor an LA approach toward bone debridement in the initial treatment. Therapeutic level III.

Quantitative evaluation of palatal bone thickness for the placement of orthodontic miniscrews in adults with different facial types

PubMed Central

Wang, Yunji; Qiu, Ye; Liu, Henglang; He, Jinlong; Fan, Xiaoping

2017-01-01

Objectives: To quantitatively evaluate palatal bone thickness in adults with different facial types using cone beam computed tomography (CBCT). Methods: The CBCT volumetric data of 123 adults (mean age, 26.8 years) collected between August 2014 and August 2016 was retrospectively studied. The subjects were divided into a low-angle group (39 subjects), a normal-angle group (48 subjects) and a high-angle group (36 subjects) based on facial types assigned by cephalometric radiography. The thickness of the palatal bone was assessed at designated points. A repeated-measure analysis of variance (rm-ANOVA) test was used to test the relationship between facial types and palatal bone thickness. Results: Compared to the low-angle group, the high-angle group had significantly thinner palatal bones (p<0.05), except for the anterior-midline, anterior-medial and middle-midline areas. Conclusion: The safest zone for the placement of microimplants is the anterior part of the paramedian palate. Clinicians should pay special attention to the probability of thinner bone plates and the risk of perforation in high-angle patients. PMID:28917071

Bony defect of palate and vomer in submucous cleft palate patients.

PubMed

Ren, S; Ma, L; Zhou, X; Sun, Z

2015-01-01

The aim of this study was to visualize bony defects of the palate and vomer in submucous cleft palate patients (SMCP) by three-dimensional (3D) computed tomography (CT) reconstruction and to classify the range of bony defects. Forty-eight consecutive non-operated SMCP patients were included. Diagnosis was based on the presence of at least one of three classical signs of SMCP: bifid uvula, a translucent zone in the midline of the soft palate, and a palpable 'V' notch on the posterior border of the bony palate. Patients were imaged using spiral CT. 3D reconstruction models were created of the palate and vomer. The sagittal extent of the bony cleft in SMCP was classified into four types: type I, no V-shaped hard palate cleft (8.3%); type II, cleft involving the partial palate (43.8%); type III, cleft involving the complete palate and extending to the incisive foramen (43.8%); type IV, cleft involving the complete palate and the alveolar bone (4.2%). The extent of the vomer defect was classified into three types: type A, vomer completely fused with the palate (8.3%); type B, vomer partially fused with the palate (43.8%); type C, vomer not fused with the palate up to the incisive foramen (47.9%). Significant variability in hard palate defects in SMCP is the rule rather than the exception. The association of velopharyngeal insufficiency with anatomical malformations may be complex. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Phenotypic characterization of Grm1crv4 mice reveals a functional role for the type 1 metabotropic glutamate receptor in bone mineralization.

PubMed

Musante, Ilaria; Mattinzoli, Deborah; Otescu, Lavinia Alexandra; Bossi, Simone; Ikehata, Masami; Gentili, Chiara; Cangemi, Giuliana; Gatti, Cinzia; Emionite, Laura; Messa, Piergiorgio; Ravazzolo, Roberto; Rastaldi, Maria Pia; Riccardi, Daniela; Puliti, Aldamaria

2017-01-01

Recent increasing evidence supports a role for neuronal type signaling in bone. Specifically glutamate receptors have been found in cells responsible for bone remodeling, namely the osteoblasts and the osteoclasts. While most studies have focused on ionotropic glutamate receptors, the relevance of the metabotropic glutamate signaling in bone is poorly understood. Specifically type 1 metabotropic glutamate (mGlu1) receptors are expressed in bone, but the effect of its ablation on skeletal development has never been investigated. Here we report that Grm1 crv4/crv4 mice, homozygous for an inactivating mutation of the mGlu1 receptor, and mainly characterized by ataxia and renal dysfunction, exhibit decreased body weight, bone length and bone mineral density compared to wild type (WT) animals. Blood analyses of the affected mice demonstrate the absence of changes in circulating factors, such as vitamin D and PTH, suggesting renal damage is not the main culprit of the skeletal phenotype. Cultures of osteoblasts lacking functional mGlu1 receptors exhibit less homogeneous collagen deposition than WT cells, and present increased expression of osteocalcin, a marker of osteoblast maturation. These data suggest that the skeletal damage is directly linked to the absence of the receptor, which in turn leads to osteoblasts dysfunction and earlier maturation. Accordingly, skeletal histomorphology suggests that Grm1 crv4/crv4 mice exhibit enhanced bone maturation, resulting in premature fusion of the growth plate and shortened long bones, and further slowdown of bone apposition rate compared to the WT animals. In summary, this work reveals novel functions of mGlu1 receptors in the bone and indicates that in osteoblasts mGlu1 receptors are necessary for production of normal bone matrix, longitudinal bone growth, and normal skeletal development. Copyright © 2016 Elsevier Inc. All rights reserved.

Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report.

PubMed

Rosenberg, Emily; Buchtel, Lindsey

2016-01-01

A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung.

Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep.

PubMed

Liu, Tie; Wu, Gang; Wismeijer, Daniel; Gu, Zhiyuan; Liu, Yuelian

2013-09-01

As an alternative to an autologous bone graft, deproteinized bovine bone (DBB) is widely used in the clinical dentistry. Although DBB provides an osteoconductive scaffold, it is not capable of enhancing bone regeneration because it is not osteoinductive. In order to render DBB osteoinductive, bone morphogenetic protein 2 (BMP-2) has previously been incorporated into a three dimensional reservoir (a biomimetic calcium phosphate coating) on DBB, which effectively promoted the osteogenic response by the slow delivery of BMP-2. The aim of this study was to investigate the therapeutic effectiveness of such coating on the DBB granules in repairing a large cylindrical bone defect (8 mm diameter, 13 mm depth) in sheep. Eight groups were randomly assigned to the bone defects: (i) no graft material; (ii) autologous bone; (iii) DBB only; (iv) DBB mixed with autologous bone; (v) DBB bearing adsorbed BMP-2; (vi) DBB bearing a coating but no BMP-2; (vii) DBB bearing a coating with adsorbed BMP-2; and (viii) DBB bearing a coating-incorporated depot of BMP-2. 4 and 8 weeks after implantation, samples were withdrawn for a histological and a histomorphometric analysis. Histological results confirmed the excellent biocompatibility and osteoconductivity of all the grafts tested. At 4 weeks, DBB mixed with autologous bone or functionalized with coating-incorporated BMP-2 showed more newly-formed bone than the other groups with DBB. At 8 weeks, the volume of newly-formed bone around DBB that bore a coating-incorporated depot of BMP-2 was greatest among the groups with DBB, and was comparable to the autologous bone group. The use of autologous bone and BMP-2 resulted in more bone marrow formation. Multinucleated giant cells were observed in the resorption process around DBB, whereas histomorphometric analysis revealed no significant degradation of DBB. In conclusion, it was shown that incorporating BMP-2 into the calcium phosphate coating of DBB induced strong bone formation around DBB for repairing a critical-sized bone defect. Copyright © 2013 Elsevier Inc. All rights reserved.

Bone Cancer—Patient Version

Cancer.gov

Bone cancer is rare and includes several types. Some bone cancers, including osteosarcoma and Ewing sarcoma, are seen most often in children and young adults. Start here to find information on bone cancer treatment, research, and statistics.

Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

PubMed Central

Li, Feng; Wang, Xujun; Niyibizi, Christopher

2010-01-01

Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets.

PubMed

Quarfordt, S H; Frank, A; Shames, D M; Berman, M; Steinberg, D

1970-12-01

Transport of plasma-free fatty acids (FFA) and of fatty acids in triglycerides of plasma very low density lipoproteins (VLDL-TGFA) was studied in two normal subjects, five patients with type IV hyperlipoproteinemia, and two patients with type I hyperlipoproteinemia. After intravenous pulse-labeling with albumin-bound 1-palmitate-(14)C, specific radioactivity of plasma FFA and VLDL-TGFA were determined at intervals up to 24 hr. The results were analyzed using several different multicompartmental models each compatible with the experimental data. Fractional transport of VLDL-TGFA was distinctly lower (no overlap) in the type IV patients than in the control subjects, both on a usual balanced diet (40% of calories from carbohydrate) and on a high-carbohydrate diet (80% of calories). However, net or total transport of VLDL-TGFA in the type IV patients was not clearly distinguishable from that in the control subjects, there being considerable overlap on either diet. The results suggest that in this group of type IV patients the underlying defect leading to the increased pool size of VLDL-TGFA is not overproduction but a relative defect in mechanisms for removal of VLDL-TGFA. Since some of these type IV patients had only a moderate degree of hypertriglyceridemia at the time they were studied, and since it is not established that patients with the type IV phenotype constitute a biochemically homogeneous population, the present results should not be generalized. Four studies were done (in two control subjects and two type IV patients) in which the kinetic parameters in the same individual were determined on the balanced diet and on the high-carbohydrate diet. All subjects showed an increase in VLDL-TGFA pool size. Using two of the models for analysis, all showed an increase in net transport of VLDL-TGFA; using the third model, three of the four studies showed an increase in VLDL-TGFA transport. The results are compatible with the interpretation that the carbohydrate-induced increase in VLDL-TGFA, both in controls and type IV patients, is at least in part due to an increased rate of production of VLDL-TGFA. The magnitude of the increase was approximately the same in controls and patients. Thus, metabolic adjustment to a high-carbohydrate regimen in these type IV patients may not be basically different from that in normal controls; the higher levels of VLDL-TGFA reached may simply be another reflection of a defective removal mechanism. An alternative interpretation, compatible with the data, would involve both a carbohydrate-induced increase in fractional rate of release of VLDL-TGFA from liver to plasma and a decrease in fractional removal of VLDL-TGFA from plasma without increase in net production rate. The simpler hypothesis of a single primary effect on net VLDL-TGFA production from FFA seems more likely.

Alport Syndrome Diagnosis

MedlinePlus

... the presence or absence of the type IV collagen alpha-3, alpha-4 and alpha-5 chains ( ... linked Alport syndrome) is suspected. The type IV collagen alpha-5 chain (COL4A5) is normally present in ...

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis

PubMed Central

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L.; Wang, Yanlin

2014-01-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. Since chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly fewer bone marrow-derived fibroblasts accumulated in the kidney of CXCR6 knockout mice in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type mice. CXCR6 deficiency inhibited total collagen deposition and suppressed expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, wild type mice engrafted with CXCR6−/− bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with wild-type mice engrafted with CXCR6+/+ bone marrow cells. Transplant of wild type bone marrow into CXCR6−/− recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may play important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis. PMID:24646857

Bone scan as a screening test for missed fractures in severely injured patients.

PubMed

Lee, K-J; Jung, K; Kim, J; Kwon, J

2014-12-01

In many cases, patients with severe blunt trauma have multiple fractures throughout the body. These fractures are not often detectable by history or physical examination, and their diagnosis can be delayed or even missed. Thus, screening test fractures of the whole body is required after initial management. We performed this study to evaluate the reliability of bone scans for detecting missed fractures in patients with multiple severe traumas and we analyzed the causes of missed fractures by using bone scan. A bone scan is useful as a screening test for fractures of the entire body of severe trauma patients who are passed the acute phase. We reviewed the electronic medical records of severe trauma patients who underwent a bone scan from September 2009 to December 2010. Demographic and medical data were compared and statistically analyzed to determine whether missed fractures were detected after bone scan in the two groups. A total of 382 patients who had an injury severity score [ISS] greater than 16 points with multiple traumas visited the emergency room. One hundred and thirty-one patients underwent bone scan and 81 patients were identified with missed fractures by bone scan. The most frequent location for missed fractures was the rib area (55 cases, 41.98%), followed by the extremities (42 cases, 32.06%). The missed fractures that required surgery or splint were most common in extremities (11 cases). In univariate analysis, higher ISS scores and mechanism of injury were related with the probability that missed fractures would be found with a bone scan. The ISS score was statistically significant in multivariate analysis. Bone scan is an effective method of detecting missed fractures among patients with multiple severe traumas. Level IV, retrospective study. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Evaluation of Bone Atrophy After Treatment of Forearm Fracture Using Nonlinear Finite Element Analysis: A Comparative Study of Locking Plates and Conventional Plates.

PubMed

Matsuura, Yusuke; Rokkaku, Tomoyuki; Suzuki, Takane; Thoreson, Andrew Ryan; An, Kai-Nan; Kuniyoshi, Kazuki

2017-08-01

Forearm diaphysis fractures are usually managed by open reduction internal fixation. Recently, locking plates have been used for treatment. In the long-term period after surgery, some patients present with bone atrophy adjacent to the plate. However, a comparison of locking and conventional plates as a cause of atrophy has not been reported. The aim of this study was to investigate long-term bone atrophy associated with use of locking and conventional plates for forearm fracture treatment. In this study we included 15 patients with forearm fracture managed by either locking or conventional plates and with more than 5 years of follow-up. Computed tomographic imaging of both forearms was performed to assess bone thickness and local bone mineral density and to predict bone strength without plate reinforcement based on finite element analysis. Mean patient age at surgery was 48.0 years. Eight patients underwent reduction with fixed locking plates and were followed up for a mean of 79.5 months; the remaining 7 patients were treated with conventional plates and were followed up for a mean of 105.0 months. Compared with the conventional plate group, the locking plate group had the same fractured limb-contralateral limb ratio of cortex bone thickness, but had significantly lower ratios of mineral density adjacent to the plate and adjusted bone strength. This study demonstrated bone atrophy after locking plate fixation for forearm fractures. Treatment plans for forearm fracture should take into consideration the impact of bone atrophy long after plate fixation. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

A novel classification of frontal bone fractures: The prognostic significance of vertical fracture trajectory and skull base extension.

PubMed

Garg, Ravi K; Afifi, Ahmed M; Gassner, Jennifer; Hartman, Michael J; Leverson, Glen; King, Timothy W; Bentz, Michael L; Gentry, Lindell R

2015-05-01

The broad spectrum of frontal bone fractures, including those with orbital and skull base extension, is poorly understood. We propose a novel classification scheme for frontal bone fractures. Maxillofacial CT scans of trauma patients were reviewed over a five year period, and frontal bone fractures were classified: Type 1: Frontal sinus fracture without vertical extension. Type 2: Vertical fracture through the orbit without frontal sinus involvement. Type 3: Vertical fracture through the frontal sinus without orbit involvement. Type 4: Vertical fracture through the frontal sinus and ipsilateral orbit. Type 5: Vertical fracture through the frontal sinus and contralateral or bilateral orbits. We also identified the depth of skull base extension, and performed a chart review to identify associated complications. 149 frontal bone fractures, including 51 non-vertical frontal sinus (Type 1, 34.2%) and 98 vertical (Types 2-5, 65.8%) fractures were identified. Vertical fractures penetrated the middle or posterior cranial fossa significantly more often than non-vertical fractures (62.2 v. 15.7%, p = 0.0001) and had a significantly higher mortality rate (18.4 v. 0%, p < 0.05). Vertical fractures with frontal sinus and orbital extension, and fractures that penetrated the middle or posterior cranial fossa had the strongest association with intracranial injuries, optic neuropathy, disability, and death (p < 0.05). Vertical frontal bone fractures carry a worse prognosis than frontal bone fractures without a vertical pattern. In addition, vertical fractures with extension into the frontal sinus and orbit, or with extension into the middle or posterior cranial fossa have the highest complication rate and mortality. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Urinary type IV collagen excretion predicts subsequent declining renal function in type 2 diabetic patients with proteinuria.

PubMed

Katavetin, Pisut; Katavetin, Paravee; Susantitaphong, Paweena; Townamchai, Natavudh; Tiranathanagul, Khajohn; Tungsanga, Kriang; Eiam-Ong, Somchai

2010-08-01

Baseline urinary type IV collagen excretion was negatively correlated with the subsequent GFR change (r(s)=-0.39, p=0.04) in our cohort of 30 type 2 diabetic patients with proteinuria. Therefore, it could be used to predict subsequent declining renal function in type 2 diabetic patients with proteinuria. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Pain and Paget's Disease of Bone

MedlinePlus

... Disease of Bone Pain and Paget’s Disease of Bone Types of Pain Paget’s disease can cause several ... Last Reviewed 2015-05 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, ...

Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation.

PubMed

Marini, Joan C; Reich, Adi; Smith, Simone M

2014-08-01

Osteogenesis imperfecta or 'brittle bone disease' has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for osteogenesis imperfecta as a collagen-related disorder, where most cases are due to autosomal dominant type I collagen defects, while rare, mostly recessive, forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development, and future of this paradigm shift in the understanding of osteogenesis imperfecta. Bone-restricted interferon-induced transmembrane (IFITM)-like protein (BRIL) and pigment epithelium-derived factor (PEDF) defects cause types V and VI osteogenesis imperfecta via defective bone mineralization, while defects in cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1), and cyclophilin B (CYPB) cause types VII-IX osteogenesis imperfecta via defective collagen post-translational modification. Heat shock protein 47 (HSP47) and FK506-binding protein-65 (FKBP65) defects cause types X and XI osteogenesis imperfecta via aberrant collagen crosslinking, folding, and chaperoning, while defects in SP7 transcription factor, wingless-type MMTV integration site family member 1 (WNT1), trimeric intracellular cation channel type b (TRIC-B), and old astrocyte specifically induced substance (OASIS) disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase bone morphogenetic protein 1 (BMP1) causes type XII osteogenesis imperfecta due to altered collagen maturation/processing. Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of osteogenesis imperfecta types by shared mechanism to simplify current nosology, and has prodded investigations into common pathways in osteogenesis imperfecta. Such investigations could yield critical information on cellular and bone tissue mechanisms and translate to new mechanistic insight into clinical therapies for patients.

Leptin regulates bone formation via the sympathetic nervous system

NASA Technical Reports Server (NTRS)

Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

2002-01-01

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

Two type IV pili of Vibrio parahaemolyticus play different roles in biofilm formation.

PubMed

Shime-Hattori, Akiko; Iida, Tetsuya; Arita, Michiko; Park, Kwon-Sam; Kodama, Toshio; Honda, Takeshi

2006-11-01

Vibrio parahaemolyticus RIMD2210633 has two sets of type IV-A pilus genes. One set is similar to that found in other Gram-negative bacteria, such as Pseudomonas aeruginosa, Vibrio cholerae (chitin-regulated pilus; ChiRP), and Vibrio vulnificus. The other is homologous to the genes for the mannose-sensitive hemagglutinin (MSHA) pilus. In this study, we analyzed the effects of the deletions in the pilin genes for each type IV pilus (the ChiRP and the MSHA pilus) on biofilm formation. Although the MSHA pilin mutant formed aggregates, the number of bacteria that attached directly to the coverslip was reduced, suggesting that this pilus contributes to the bacterial attachment to the surface of the coverslip. In contrast, the ChiRP mutant attached to the surface of the coverslip, but did not form aggregates, suggesting that ChiRP plays a role in bacterial agglutination during biofilm formation. These results suggest that the two type IV pili of V. parahaemolyticus contribute to biofilm formation in different ways. Both mutants showed a lower fitness for adsorption onto chitin particles than that of the wild type. Collectively, these data suggest that the use of two type IV pili is a refined strategy of V. parahaemolyticus for survival in natural environments.

Direct comparison of progenitor cells derived from adipose, muscle, and bone marrow from wild-type or craniosynostotic rabbits

PubMed Central

GM, Cooper; EL, Lensie; JJ, Cray; MR, Bykowski; GE, DeCesare; MA, Smalley; MP, Mooney; PG, Campbell; JE, Losee

2010-01-01

Background Reports have identified cells capable of osteogenic differentiation in bone marrow, muscle, and adipose tissues, but there are few direct comparisons of these different cell-types. Also, few have investigated the potential connection between a tissue-specific pathology and cells derived from seemingly unrelated tissues. Here, we compare cells isolated from wild-type rabbits or rabbits with nonsyndromic craniosynostosis, defined as the premature fusion of one or more of the cranial sutures. Methods Cells were derived from bone marrow, adipose, and muscle of 10 day-old wild-type rabbits (WT; n=17) or from age-matched rabbits with familial nonsyndromic craniosynostosis (CS; n=18). Cells were stimulated with bone morphogenetic protein 4 (BMP4) and alkaline phosphatase expression and cell proliferation were assessed. Results In WT rabbits, cells derived from muscle had more alkaline phosphatase activity than cells derived from either adipose or bone marrow. The cells derived from CS rabbit bone marrow and muscle were significantly more osteogenic than WT. Adipose-derived cells demonstrated no significant differences. While muscle-derived cells were most osteogenic in WT rabbits, bone marrow-derived cells were most osteogenic in CS rabbits. Conclusions Results suggest that cells from different tissues have different potentials for differentiation. Furthermore, cells derived from rabbits with craniosynostosis were different from wild-type derived cells. Interestingly, cells derived from the craniosynostotic rabbits were not uniformly more responsive compared with wild-type cells, suggesting that specific tissue-derived cells may react differently in individuals with craniosynostosis. PMID:20871482

A Split-Luciferase-Based Trimer Formation Assay as a High-throughput Screening Platform for Therapeutics in Alport Syndrome.

PubMed

Omachi, Kohei; Kamura, Misato; Teramoto, Keisuke; Kojima, Haruka; Yokota, Tsubasa; Kaseda, Shota; Kuwazuru, Jun; Fukuda, Ryosuke; Koyama, Kosuke; Matsuyama, Shingo; Motomura, Keishi; Shuto, Tsuyoshi; Suico, Mary Ann; Kai, Hirofumi

2018-05-17

Alport syndrome is a hereditary glomerular disease caused by mutation in type IV collagen α3-α5 chains (α3-α5(IV)), which disrupts trimerization, leading to glomerular basement membrane degeneration. Correcting the trimerization of α3/α4/α5 chain is a feasible therapeutic approach, but is hindered by lack of information on the regulation of intracellular α(IV) chain and the absence of high-throughput screening (HTS) platforms to assess α345(IV) trimer formation. Here, we developed sets of split NanoLuc-fusion α345(IV) proteins to monitor α345(IV) trimerization of wild-type and clinically associated mutant α5(IV). The α345(IV) trimer assay, which satisfied the acceptance criteria for HTS, enabled the characterization of intracellular- and secretion-dependent defects of mutant α5(IV). Small interfering RNA-based and chemical screening targeting the ER identified several chemical chaperones that have potential to promote α345(IV) trimer formation. This split luciferase-based trimer formation assay is a functional HTS platform that realizes the feasibility of targeting α345(IV) trimers to treat Alport syndrome. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nanoscale Morphology of Type I Collagen is Altered in the Brtl Mouse Model of Osteogenesis Imperfecta

PubMed Central

Wallace, Joseph M.; Orr, Bradford G.; Marini, Joan C.; Banaszak Holl, Mark M.

2010-01-01

Bone has a complex hierarchical structure that has evolved to serve structural and metabolic roles in the body. Due to the complexity of bone structure and the number of diseases which affect the ultrastructural constituents of bone, it is important to develop quantitative methods to assess bone nanoscale properties. Autosomal dominant Osteogenesis Imperfecta results predominantly from glycine substitutions (80%) and splice site mutations (20%) in the genes encoding the α1 or α2 chains of Type I collagen. Genotype-phenotype correlations using over 830 collagen mutations have revealed that lethal mutations are located in regions crucial for collagen-ligand binding in the matrix. However, few of these correlations have been extended to collagen structure in bone. Here, an atomic force microscopy-based approach was used to image and quantitatively analyze the D-periodic spacing of Type I collagen fibrils in femora from heterozygous (Brtl/+) mice (α1(I)G349C), compared to wild type (WT) littermates. This disease system has a well-defined change in the col1α1 allele, leading to a well characterized alteration in collagen protein structure, which are directly related to altered Type I collagen nanoscale morphology, as measured by the D-periodic spacing. In Brtl/+ bone, the D-periodic spacing shows significantly greater variability on average and along the length of the bone compared to WT, although the average spacing was unchanged. Brtl/+ bone also had a significant difference in the population distribution of collagen D-period spacings. These changes may be due to the mutant collagen structure, or to the heterogeneity of collagen monomers in the Brtl/+ matrix. These observations at the nanoscale level provide insight into the structural basis for changes present in bone composition, geometry and mechanical integrity in Brtl/+ bones. Further studies are necessary to link these morphological observations to nanoscale mechanical integrity. PMID:20696252

Diversity, assembly and regulation of archaeal type IV pili-like and non-type-IV pili-like surface structures.

PubMed

Lassak, Kerstin; Ghosh, Abhrajyoti; Albers, Sonja-Verena

2012-01-01

Archaea have evolved fascinating surface structures allowing rapid adaptation to changing environments. The archaeal surface appendages display such diverse biological roles as motility, adhesion, biofilm formation, exchange of genetic material and species-specific interactions and, in turn, increase fitness of the cells. Intriguingly, despite sharing the same functions with their bacterial counterparts, the assembly mechanism of many archaeal surface structures is rather related to assembly of bacterial type IV pili. This review summarizes our state-of-the-art knowledge about unique structural and biochemical properties of archaeal surface appendages with a particular focus on archaeal type IV pili-like structures. The latter comprise not only widely distributed archaella (formerly known as archaeal flagella), but also different highly specialized archaeal pili, which are often restricted to certain species. Recent findings regarding assembly mechanisms, structural aspects and physiological roles of these type IV pili-like structures will be discussed in detail. Recently, first regulatory proteins involved in transition from both planktonic to sessile lifestyle and in assembly of archaella were identified. To conclude, we provide novel insights into regulatory mechanisms underlying the assembly of archaeal surface structures. Copyright © 2012. Published by Elsevier Masson SAS.

Effect of foot shape on the three-dimensional position of foot bones.

PubMed

Ledoux, William R; Rohr, Eric S; Ching, Randal P; Sangeorzan, Bruce J

2006-12-01

To eliminate some of the ambiguity in describing foot shape, we developed three-dimensional (3D), objective measures of foot type based on computerized tomography (CT) scans. Feet were classified via clinical examination as pes cavus (high arch), neutrally aligned (normal arch), asymptomatic pes planus (flat arch with no pain), or symptomatic pes planus (flat arch with pain). We enrolled 10 subjects of each foot type; if both feet were of the same foot type, then each foot was scanned (n=65 total). Partial weightbearing (20% body weight) CT scans were performed. We generated embedded coordinate systems for each foot bone by assuming uniform density and calculating the inertial matrix. Cardan angles were used to describe five bone-to-bone relationships, resulting in 15 angular measurements. Significant differences were found among foot types for 12 of the angles. The angles were also used to develop a classification tree analysis, which determined the correct foot type for 64 of the 65 feet. Our measure provides insight into how foot bone architecture differs between foot types. The classification tree analysis demonstrated that objective measures can be used to discriminate between feet with high, normal, and low arches. Copyright (c) 2006 Orthopaedic Research Society.

[Influencing factors for trauma-induced tibial infection in underground coal mine].

PubMed

Meng, W Z; Guo, Y J; Liu, Z K; Li, Y F; Wang, G Z

2016-07-20

Objective: To investigate the influencing factors for trauma-induced tibial infection in underground coal mine. Methods: A retrospective analysis was performed for the clinical data of 1 090 patients with tibial fracture complicated by bone infection who were injured in underground coal mine and admitted to our hospital from January 1995 to August 2015, including the type of trauma, injured parts, severity, and treatment outcome. The association between risk factors and infection was analyzed. Results: Among the 1 090 patients, 357 had the clinical manifestations of acute and chronic bone infection, 219 had red and swollen legs with heat pain, and 138 experienced skin necrosis, rupture, and discharge of pus. The incidence rates of tibial infection from 1995 to 2001, from 2002 to 2008, and from 2009 to 2015 were 31%, 26.9%, and 20.2%, respectively. The incidence rate of bone infection in the proximal segment of the tibia was significantly higher than that in the middle and distal segments (42.1% vs 18.9%/27.1%, P <0.01) . As for patients with different types of trauma (Gustilo typing) , the patients with type III fracture had a significantly higher incidence rate of bone infection than those with type I/II infection (52.8% vs 21.8%/24.6%, P <0.01) . The incidence rates of bone infection after bone traction, internal fixation with steel plates, fixation with external fixator, and fixation with intramedullary nail were 20.7%, 43.5%, 21.4%, and 26.1%, respectively, suggesting that internal fixation with steel plates had a significantly higher incidence rate of bone infection than other fixation methods ( P <0.01) . The multivariate logistic regression analysis showed that the position of tibial fracture and type of fracture were independent risk factors for bone infection. Conclusion: There is a high incidence rate of trauma-induced tibial infection in workers in underground coal mine. The position of tibial fracture and type of fracture are independent risk factors for bone infection. Vacuum sealing drainage and Ilizarov technique can achieve a satisfactory therapeutic effect.

Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1

PubMed Central

Xiao, Qian; Jiang, Yan; Liu, Qingbo; Yue, Jiao; Liu, Chunying; Zhao, Xiaotong; Qiao, Yuemei; Ji, Hongbin; Chen, Jianfeng; Ge, Gaoxiang

2015-01-01

Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV. PMID:25992553

Regulatory elements driving the expression of skeletal lineage reporters differ during bone development and adulthood.

PubMed

Stiers, Pieter-Jan; van Gastel, Nick; Moermans, Karen; Stockmans, Ingrid; Carmeliet, Geert

2017-12-01

To improve bone healing or regeneration more insight in the fate and role of the different skeletal cell types is required. Mouse models for fate mapping and lineage tracing of skeletal cells, using stage-specific promoters, have advanced our understanding of bone development, a process that is largely recapitulated during bone repair. However, validation of these models is often only performed during development, whereas proof of the activity and specificity of the used promoters during the bone regenerative process is limited. Here, we show that the regulatory elements of the 6kb collagen type II promoter are not adequate to drive gene expression during bone repair. Similarly, the 2.3kb promoter of collagen type I lacks activity in adult mice, but the 3.2kb promoter is suitable. Furthermore, Cre-mediated fate mapping allows the visualization of progeny, but this label retention may hinder to distinguish these cells from ones with active expression of the marker at later time points. Together, our results show that the lineage-specific regulatory elements driving gene expression during bone development differ from those required later in life and during bone repair, and justify validation of lineage-specific cell tracing and gene silencing strategies during fracture healing and bone regenerative applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism.

PubMed

Cao, Yixuan; Wang, Yongqiang; Sprangers, Sara; Picavet, Daisy I; Glogauer, Michael; McCulloch, Christopher A; Everts, Vincent

2017-08-01

Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP + osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm 2 ; p < 0.05), as were nuclear size and the surface area of cytoplasm. The nuclei of adseverin null osteoclasts exhibited more heterochromatin (31 ± 3%) than wild-type cells (8 ± 1%), suggesting that adseverin affects cell differentiation. The data indicate that in healthy, developing tissues, adseverin contributes to the regulation of osteoclast structure but not to bone metabolism in vivo.

Root canal morphology of South Asian Indian maxillary molar teeth

PubMed Central

Singh, Shishir; Pawar, Mansing

2015-01-01

Objective: The objective was to study the root canal morphology of South Asian Indian Maxillary molars using a tooth clearing technique. Materials and Methods: Hundred teeth each comprising of first, second, and third molars collected from different dental schools and clinics in India were subjected to standard dye penetration, decalcification and clearing procedure before being studied. Results: The first molar mesiobuccal roots exhibited 69% Type I, 24% Type II, 4% Type IV, 2% Type V, and 1% exhibited a Vertuccis Type VIII canal anatomy. In the group with three separate roots the second molar mesiobuccal roots in exhibited 80.6% Type I, 15.3% Type II, 2.7% Type IV, and 1.4% Type V canal anatomy while the third molars mesiobuccal roots exhibited 57.4% Type I, 32% Type II, 2.1% Type III, 8.5% Type IV, 1% had a Type V canal anatomy in the similar group. Conclusion: A varied root canal anatomy was seen in the mesiobuccal root canal of the maxillary molars. PMID:25713497

Human Studies of Vertical and Horizontal Alveolar Ridge Augmentation Comparing Different Types of Bone Graft Materials: A Systematic Review.

PubMed

Chavda, Suraj; Levin, Liran

2018-02-01

Alveolar ridge augmentation can be completed with various types of bone augmentation materials (autogenous, allograft, xenograft, and alloplast). Currently, autogenous bone is labeled as the "gold standard" because of faster healing times and integration between native and foreign bone. No systematic review has currently determined whether there is a difference in implant success between various bone augmentation materials. The purpose of this article was to systematically review comparative human studies of vertical and horizontal alveolar ridge augmentation comparing different types of bone graft materials (autogenous, allograft, xenograft, and alloplast). A MEDLINE search was conducted under the 3 search concepts of bone augmentation, dental implants, and alveolar ridge augmentation. Studies pertaining to socket grafts or sinus lifts were excluded. Case reports, small case series, and review papers were excluded. A bias assessment tool was applied to the final articles. Overall, 219 articles resulted from the initial search, and 9 articles were included for final analysis. There were no discernible differences in implant success between bone augmentation materials. Generally, patients preferred nonautogenous bone sources as there were fewer hospital days, less pain, and better recovery time. Two articles had industrial support; however, conclusions of whether that support influenced the outcomes could not be determined. Future comparative studies should compare nonautogenous bone sources and have longer follow-up times.

Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta.

PubMed

Palomo, Telma; Andrade, Maria C; Peters, Barbara S E; Reis, Fernanda A; Carvalhaes, João Tomás A; Glorieux, Francis H; Rauch, Frank; Lazaretti-Castro, Marise

2016-01-01

Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.

Stem cells and niemann pick disease.

PubMed

Andolina, Marino

2014-05-01

Niemann Pick A disease causes a progressive accumulation of sphyngomyelin in several organs and the survival of the patients is usually limited to three years. We describe the outcome of a patient suffering from Niemann Pick A disease, who first underwent an haploidentical bone marrow transplantation, and then intrathecal and I.V injections of mesenchymal cells. While the outcome of bone marrow transplantation was a complete failure, one month after the treatment with the mesenchymal cells the patient improved from the psychomotor and the parenchymal storage perspective. When hypersplenism was solved platelets rose quickly from 20,000 to 120,000/microliter. Therefore cellular therapy should be considered as a possible choice of treatment of NPA disease.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

PubMed

Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

2011-12-01

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

Calorie restriction and bone health in young, overweight individuals.

PubMed

Redman, Leanne M; Rood, Jennifer; Anton, Stephen D; Champagne, Catherine; Smith, Steven R; Ravussin, Eric

2008-09-22

Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life. Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR + EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months. Mean +/- SE body weight was reduced by -1.0% +/- 1.1% (control), -10.4% +/- 0.9% (CR), -10.0% +/- 0.8% (CR + EX), and -13.9% +/- 0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23% +/- 10%; CR + EX, 22% +/- 9%; and LCD, 74% +/- 16% vs control, 4% +/- 10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23% +/- 10%) but were unchanged in the CR + EX, LCD, and control groups. Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health. clinicaltrials.gov Identifier: NCT00099151.

Embalmed and fresh frozen human bones in orthopedic cadaveric studies: which bone is authentic and feasible?

PubMed Central

2012-01-01

Background and purpose The most frequently used bones for mechanical testing of orthopedic and trauma devices are fresh frozen cadaveric bones, embalmed cadaveric bones, and artificial composite bones. Even today, the comparability of these different bone types has not been established. Methods We tested fresh frozen and embalmed cadaveric femora that were similar concerning age, sex, bone mineral density, and stiffness. Artificial composite femora were used as a reference group. Testing parameters were pullout forces of cortex and cancellous screws, maximum load until failure, and type of fracture generated. Results Stiffness and type of fracture generated (Pauwels III) were similar for all 3 bone types (fresh frozen: 969 N/mm, 95% confidence interval (CI): 897–1,039; embalmed: 999 N/mm, CI: 875–1,121; composite: 946 N/mm, CI: 852–1,040). Furthermore, no significant differences were found between fresh frozen and embalmed femora concerning pullout forces of cancellous screws (fresh frozen: 654 N, CI: 471–836; embalmed: 595 N, CI: 365–823) and cortex screws (fresh frozen: 1,152 N, CI: 894–1,408; embalmed: 1,461 N, CI: 880–2,042), and axial load until failure (fresh frozen: 3,427 N, CI: 2,564–4290; embalmed: 3,603 N, CI: 2,898–4,306). The reference group showed statistically significantly different results for pullout forces of cancellous screws (2,344 N, CI: 2,068–2,620) and cortex screws (5,536 N, CI: 5,203–5,867) and for the axial load until failure (> 7,952 N). Interpretation Embalmed femur bones and fresh frozen bones had similar characteristics by mechanical testing. Thus, we suggest that embalmed human cadaveric bone is a good and safe option for mechanical testing of orthopedic and trauma devices. PMID:22978564

The pedicle screw-rod system is an acceptable method of reconstructive surgery after resection of sacroiliac joint tumours

PubMed Central

Zhou, Yi-Jun; Yunus, Akbar; Tian, Zheng; Chen, Jiang-Tao; Wang, Chong; Xu, Lei-Lei

2016-01-01

Hemipelvic resections for primary bone tumours require reconstruction to restore weight bearing along anatomic axes. However, reconstruction of the pelvic arch remains a major surgical challenge because of the high rate of associated complications. We used the pedicle screw-rod system to reconstruct the pelvis, and the purpose of this investigation was to assess the oncology, functional outcome and complication rate following this procedure. The purpose of this study was to investigate the operative indications and technique of the pedicle screw-rod system in reconstruction of the stability of the sacroiliac joint after resection of sacroiliac joint tumours. The average MSTS (Musculoskeletal Tumour Society) score was 26.5 at either three months after surgery or at the latest follow-up. Seven patients had surgery-related complications, including wound dehiscence in one, infection in two, local necrosis in four (including infection in two), sciatic nerve palsy in one and pubic symphysis subluxation in one. There was no screw loosening or deep vein thrombosis occurring in this series. Using a pedicle screw-rod after resection of a sacroiliac joint tumour is an acceptable method of pelvic reconstruction because of its reduced risk of complications and satisfactory functional outcome, as well as its feasibility of reconstruction for type IV pelvis tumour resection without elaborate preoperative customisation. Level of evidence: Level IV, therapeutic study. PMID:27095944

Corrective Septorhinoplasty in Acute Nasal Bone Fractures.

PubMed

Kim, Jisung; Jung, Hahn Jin; Shim, Woo Sub

2018-03-01

Closed reduction is generally recommended for acute nasal bone fractures, and rhinoplasty is considered in cases with an unsatisfactory outcome. However, concomitant rhinoplasty with fracture reduction might achieve better surgical outcomes. This study investigated the surgical techniques and outcomes in patients who underwent rhinoplasty and fracture reduction concomitantly, during the acute stage of nasal bone fracture. Forty-five patients who underwent concomitant rhinoplasty and fracture reduction were enrolled. Nasal bone fractures were classified into three major types (type I, simple fracture; type II, fracture line that mimics nasal osteotomy; and type III, comminuted fracture) based on computed tomography images and preoperative facial images. Two independent otolaryngology-head and neck surgeons evaluated the surgical outcomes and telephone based survey were made to evaluate patients satisfaction. Among 45 patients, there were 39 males and 6 females. Type I was the commonest type of fracture with 18 patients (40%), while the most frequently used surgical technique for corrective surgery was dorsal augmentation with 44 patients (97.8%). The mean visual analogue scale satisfaction score of the surgeons and patients were 7.62 and 8, respectively, with no significant differences between fracture types. Concomitant rhinoplasty with fracture reduction can be performed for acute nasal bone fracture patients, and it might lead to better aesthetic outcomes.

HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness

DOE PAGES

Ross, Ryan D.; Mashiatulla, Maleeha; Acerbo, Alvin S.; ...

2016-05-26

Here, the G171V mutation in the low density lipoprotein receptor-related protein 5 (LRP5) leads to a high bone mass (HBM) phenotype. Studies using an HBM transgenic mouse model have consistently found increased bone mass and whole-bone strength, but little attention has been paid to bone matrix quality. The current study sought to determine if the cortical bone matrix composition differs in HBM and wild-type mice and to determine how much of the variance in bone material properties is explained by variance in matrix composition. Consistent with previous studies, HBM mice had greater cortical area, moment of inertia, ultimate force, bendingmore » stiffness, and energy to failure than wild-type animals. Interestingly, the increased energy to failure was primarily caused by a large increase in post-yield behavior, with no difference in pre-yield behavior. The HBM mice had increased mineral-to-matrix and collagen cross-link ratios, and decreased crystallinity and carbonate substitution, but no differences in crystal length, intra-fibular strains, and mineral spacing compared to wild-type controls. The largest difference in material properties was a 2-fold increase in the modulus of toughness in HBM mice. Step-wise regression analyses found weak correlations between matrix composition and material properties, and interestingly, the matrix compositional parameters associated with the material properties varied between the wild-type and HBM genotypes. Although the mechanisms controlling the paradoxical combination of more mineralized yet tougher bone in HBM mice remain to be fully explained, the findings suggest that LRP5 represents a target to not only build greater bone quantity, but also to improve bone quality.« less

HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ross, Ryan D.; Mashiatulla, Maleeha; Acerbo, Alvin S.

Here, the G171V mutation in the low density lipoprotein receptor-related protein 5 (LRP5) leads to a high bone mass (HBM) phenotype. Studies using an HBM transgenic mouse model have consistently found increased bone mass and whole-bone strength, but little attention has been paid to bone matrix quality. The current study sought to determine if the cortical bone matrix composition differs in HBM and wild-type mice and to determine how much of the variance in bone material properties is explained by variance in matrix composition. Consistent with previous studies, HBM mice had greater cortical area, moment of inertia, ultimate force, bendingmore » stiffness, and energy to failure than wild-type animals. Interestingly, the increased energy to failure was primarily caused by a large increase in post-yield behavior, with no difference in pre-yield behavior. The HBM mice had increased mineral-to-matrix and collagen cross-link ratios, and decreased crystallinity and carbonate substitution, but no differences in crystal length, intra-fibular strains, and mineral spacing compared to wild-type controls. The largest difference in material properties was a 2-fold increase in the modulus of toughness in HBM mice. Step-wise regression analyses found weak correlations between matrix composition and material properties, and interestingly, the matrix compositional parameters associated with the material properties varied between the wild-type and HBM genotypes. Although the mechanisms controlling the paradoxical combination of more mineralized yet tougher bone in HBM mice remain to be fully explained, the findings suggest that LRP5 represents a target to not only build greater bone quantity, but also to improve bone quality.« less

Ablation of the Sam68 RNA Binding Protein Protects Mice from Age-Related Bone Loss

PubMed Central

Richard, Stéphane; Torabi, Nazi; Franco, Gladys Valverde; Tremblay, Guy A; Chen, Taiping; Vogel, Gillian; Morel, Mélanie; Cléroux, Patrick; Forget-Richard, Alexandre; Komarova, Svetlana; Tremblay, Michel L; Li, Wei; Li, Ailian; Gao, Yun Jing; Henderson, Janet E

2005-01-01

The Src substrate associated in mitosis of 68 kDa (Sam68) is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism; however, its physiologic role has remained elusive. Herein we report the generation of Sam68-null mice by homologous recombination. Aged Sam68−/− mice preserved their bone mass, in sharp contrast with 12-month-old wild-type littermates in which bone mass was decreased up to approximately 75%. In fact, the bone volume of the 12-month-old Sam68−/− mice was virtually indistinguishable from that of 4-month-old wild-type or Sam68−/− mice. Sam68−/− bone marrow stromal cells had a differentiation advantage for the osteogenic pathway. Moreover, the knockdown of Sam68 using short hairpin RNA in the embryonic mesenchymal multipotential progenitor C3H10T1/2 cells resulted in more pronounced expression of the mature osteoblast marker osteocalcin when differentiation was induced with bone morphogenetic protein-2. Cultures of mouse embryo fibroblasts generated from Sam68+/+ and Sam68−/− littermates were induced to differentiate into adipocytes with culture medium containing pioglitazone and the Sam68−/− mouse embryo fibroblasts shown to have impaired adipocyte differentiation. Furthermore, in vivo it was shown that sections of bone from 12-month-old Sam68−/− mice had few marrow adipocytes compared with their age-matched wild-type littermate controls, which exhibited fatty bone marrow. Our findings identify endogenous Sam68 as a positive regulator of adipocyte differentiation and a negative regulator of osteoblast differentiation, which is consistent with Sam68 being a modulator of bone marrow mesenchymal cell differentiation, and hence bone metabolism, in aged mice. PMID:16362077

MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis.

PubMed

Hygum, Katrine; Starup-Linde, Jakob; Harsløf, Torben; Vestergaard, Peter; Langdahl, Bente L

2017-03-01

To investigate the differences in bone turnover between diabetic patients and controls. A systematic review and meta-analysis. A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (-0.10 ng/mL (-0.12, -0.08)) and the bone formation markers osteocalcin (-2.51 ng/mL (-3.01, -2.01)) and procollagen type 1 amino terminal propeptide (-10.80 ng/mL (-12.83, -8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (-0.31 U/L (-0.56, -0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this. © 2017 European Society of Endocrinology.

ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.

PubMed

Gopalaswamy, Vinaya; Dhibar, Deba Prasad; Gupta, Vipin; Arya, Ashutosh Kumar; Khandelwal, Niranjan; Bhansali, Anil; Garg, Sudhir Kumar; Agarwal, Neelam; Rao, Sudhaker D; Bhadada, Sanjay Kumar

2017-06-01

Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 μg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 μg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. Weekly teriparatide therapy (60 μg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.

MR-Based Assessment of Bone Marrow Fat in Osteoporosis, Diabetes, and Obesity

PubMed Central

Cordes, Christian; Baum, Thomas; Dieckmeyer, Michael; Ruschke, Stefan; Diefenbach, Maximilian N.; Hauner, Hans; Kirschke, Jan S.; Karampinos, Dimitrios C.

2016-01-01

Bone consists of the mineralized component (i.e., cortex and trabeculae) and the non-mineralized component (i.e., bone marrow). Most of the routine clinical bone imaging uses X-ray-based techniques and focuses on the mineralized component. However, bone marrow adiposity has been also shown to have a strong linkage with bone health. Specifically, multiple previous studies have demonstrated a negative association between bone marrow fat fraction (BMFF) and bone mineral density. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are ideal imaging techniques for non-invasively investigating the properties of bone marrow fat. In the present work, we first review the most important MRI and MRS methods for assessing properties of bone marrow fat, including methodologies for measuring BMFF and bone marrow fatty acid composition parameters. Previous MRI and MRS studies measuring BMFF and fat unsaturation in the context of osteoporosis are then reviewed. Finally, previous studies investigating the relationship between bone marrow fat, other fat depots, and bone health in patients with obesity and type 2 diabetes are presented. In summary, MRI and MRS are powerful non-invasive techniques for measuring properties of bone marrow fat in osteoporosis, obesity, and type 2 diabetes and can assist in future studies investigating the pathophysiology of bone changes in the above clinical scenarios. PMID:27445977

[Progress of Masquelet technique to repair bone defect].

PubMed

Yin, Qudong; Sun, Zhenzhong; Gu, Sanjun

2013-10-01

To summarize the progress of Masquelet technique to repair bone defect. The recent literature concerning the application of Masquelet technique to repair bone defect was extensively reviewed and summarized. Masquelet technique involves a two-step procedure. First, bone cement is used to fill the bone defect after a thorough debridement, and an induced membrane structure surrounding the spacer formed; then the bone cement is removed after 6-8 weeks, and rich cancellous bone is implanted into the induced membrane. Massive cortical bone defect is repaired by new bone forming and consolidation. Experiments show that the induced membrane has vascular system and is also rich in vascular endothelial growth factor, transforming growth factor beta1, bone morphogenetic protein 2, and bone progenitor cells, so it has osteoinductive property; satisfactory results have been achieved in clinical application of almost all parts of defects, various types of bone defect and massive defect up to 25 cm long. Compared with other repair methods, Masquelet technique has the advantages of reliable effect, easy to operate, few complications, low requirements for recipient site, and wide application. Masquelet technique is an effective method to repair bone defect and is suitable for various types of bone defect, especially for bone defects caused by infection and tumor resection.

Shelf Acetabuloplasty in the Treatment of Severe Legg-Calvé-Perthes Disease: Good Outcomes at Midterm Follow-Up

PubMed Central

Grzegorzewski, Andrzej; Synder, Marek; Kmieć, Krysztof; Krajewski, Karol; Polguj, Michał; Sibiński, Marcin

2013-01-01

The aim of the study was to retrospectively review results of operative treatment for coverage deficit of femoral head in children with severe epiphysis displacement in Legg-Calvé-Perthes (LCP) disease. The material included 23 shelf acetabuloplasty procedures for LCP disease. The average age at diagnosis was 8.1 years (range 4–12). Mean follow-up was 5.8 years (range from 2.2 to 11.2 years). Mean Reimer's index decreased statistically significantly from a mean of 32% before surgery to 10.0% at the last follow-up (P < 0.00001). The mean Wiberg center-edge angle increased also statistically significantly from a mean of 17.3° before procedure to 32.3° at the last follow-up (P < 0.00001). According to the Stulberg classification, type I was observed in 2, type II in 13, type III in 6, and type IV in 2 hips. There were no differences in the range of motion or leg length discrepancy in preoperative and postoperative standing. Partial, not significant, bone graft resorption was noted in 6 cases in the first 6–9 months after surgery. To conclude, shelf acetabuloplasty allows achieving good midterm results in the treatment of severe stages of LCP disease. The procedure improves coverage of femoral head and allows its remodelling. PMID:24377097

Stage progression of congenital cholesteatoma in children.

PubMed

Kim, Young Ho; Yoo, Jae Chul; Lee, Jun Ho; Oh, Seung-Ha; Chang, Sun O; Koo, Ja-Won; Kim, Chong Sun

2012-03-01

This study aimed to investigate the most prevalent stage in each age-group of children with congenital cholesteatoma (CC) and verify the correlation between the stage and the age of the patients for the type of CC ("closed" keratotic cyst and "open" infiltrative types). Patients diagnosed with CC between 2004 and 2009 (n = 156; 116 boys and 40 girls; mean age, 5 years and 5 months; range, 12 months-16 years and 7 months) were enrolled retrospectively. Assessment of stage and type of CC was performed with preoperative high-resolution temporal bone computed tomography and intraoperative findings. The stage of CC was determined using Potsic's staging system classified into four stages according to ossicular involvement and mastoid extension. The patients consisted of groups divided on the basis of a 2-year interval. The prevalence of stage I began to decline from the age-group of 1-2 years. In contrast, the prevalence of stages III increased from the age-group of 3-4 years and that of stage IV from the age-group 5-6 years. The prevalence of "open" infiltrative type CC increased from approximately the age of 7 years, thus showing some correlation with age but not with stage. The prevalence of CC with the advanced stage increased since the age of 2 years. Therefore, the importance of early diagnosis and treatment of CC should be more emphasized.

Differential effects of PPAR-{gamma} activation versus chemical or genetic reduction of DPP-4 activity on bone quality in mice.

PubMed

Kyle, Kimberly A; Willett, Thomas L; Baggio, Laurie L; Drucker, Daniel J; Grynpas, Marc D

2011-02-01

Patients with type 2 diabetes mellitus have an increased risk of fracture that can be further exacerbated by thiazolidinediones. A new class of antidiabetic agents control glucose through reduction of dipeptidyl peptidase-4 (DPP-4) activity; however the importance of DPP-4 for the control of bone quality has not been extensively characterized. We compared the effects of the thiazolidinedione pioglitazone and the DPP-4 inhibitor sitagliptin on bone quality in high-fat diet (HFD)-fed wild-type mice. In complementary studies, we examined bone quality in Dpp4(+/+) vs. Dpp4(-/-) mice. Pioglitazone produced yellow bones with greater bone marrow adiposity and significantly reduced vertebral bone mechanics in male, female, and ovariectomized (OVX) HFD fed female mice. Pioglitazone negatively affected vertebral volumetric bone mineral density, trabecular architecture, and mineral apposition rate in male mice. Sitagliptin treatment of HFD-fed wild-type mice significantly improved vertebral volumetric bone mineral density and trabecular architecture in female mice, but these improvements were lost in females after OVX. Genetic inactivation of Dpp4 did not produce a major bone phenotype in male and female Dpp4(-/-) mice; however, OVX Dpp4(-/-) mice exhibited significantly reduced femoral size and mechanics. These findings delineate the skeletal consequences of pharmacological and genetic reduction of DPP-4 activity and reveal significant differences in the effects of pioglitazone vs. sitagliptin vs. genetic Dpp4 inactivation on bone mechanics in mice.

Changes in biochemical markers after lower limb fractures.

PubMed

Stoffel, Karl; Engler, Hanna; Kuster, Markus; Riesen, Walter

2007-01-01

The bone remodeling sequence after bone fracture changes the concentrations of biochemical bone markers, but the relationships of fracture size and of healing time to changes in biomarkers are unclear. The present pilot study was undertaken to determine the changes found in serum bone markers after plate osteosynthesis of closed distal tibial and malleolar fractures during a study period of 24 weeks. We measured tatrate-resistant acid phosphatase (TRACP 5b), collagen type I C-terminal telopeptide (ICTP), bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), and human cartilage glycoprotein 39 (YKL-40) in 20 patients with lower limb fractures (10 malleolar, 10 tibia). A physical examination and radiographs were completed to assess evidence of union. All malleolar fractures healed within 6 weeks, whereas 2 tibial fractures did not show complete bone healing after 24 weeks. Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 microg/L; ICTP: 5.6 vs 3.3 microg/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 microg/L, and 3.5 vs 3.2 microg/L, respectively, in the malleolar fracture group). In normal bone healing, changes in bone turnover markers were primarily dependent on the fracture size. Delayed tibia fracture healing may involve a disturbance in bone remodeling.

[Alport syndrome: Hereditary nephropathy associated with mutations in genes coding for type IV collagen chains].

PubMed

Heidet, Laurence; Gubler, Marie-Claire

2016-12-01

Alport syndrome is an inherited disorder characterized by the association of a progressive haematuric nephropathy with ultrastructural abnormalities of the glomerular basement membranes, a progressive sensorineural hearing loss and sometimes ocular involvement. Its incidence is less than 1 per 5000 individuals and the disease is the cause of about 2% of end stage renal disease in Europe and the United States. Alport syndrome is clinically and genetically heterogeneous. It is related to mutations in the genes encoding one of three chains, α3, α4 α5 of type IV collagen, the main component of basement membranes, expressed in the glomerular basement membrane. COL4A5 mutations are associated with X-linked Alport syndrome, which represents 80 to 85% of cases and is more severe in boys than in girls. Mutations in COL4A3 or COL4A4 are associated with autosomal Alport syndrome. The expression of collagen chains in skin and kidney basement membranes allows for the diagnosis and characterization of the mode of transmission in most patients. It is necessary to diagnose this syndrome because its family involvement, its severity, and the importance of genetic counseling. Angiotensin blockers are increasingly prescribed in proteinuric patients. Prospective studies are needed to assess the effectiveness of these treatments on proteinuria and progression of kidney failure, and to specify indications. Animal studies have shown the potential value of different molecules (protease inhibitors, chemokine receptor blockers, transforming growth factor-β1 inhibitors, hydroxy-methyl-coenzyme A reductase inhibitors, bone morphogenetic protein-7 inhibitors), hematopoietic stem cells, and of a anti-micro-RNA. Copyright © 2016. Published by Elsevier SAS.

Loss-of-function thrombospondin-1 mutations in familial pulmonary hypertension

PubMed Central

Stearman, Robert S.; Bull, Todd M.; Calabrese, David W.; Tripp-Addison, Megan L.; Wick, Marilee J.; Broeckel, Ulrich; Robbins, Ivan M.; Wheeler, Lisa A.; Cogan, Joy D.; Loyd, James E.

2012-01-01

Most patients with familial pulmonary arterial hypertension (FPAH) carry mutations in the bone morphogenic protein receptor 2 gene (BMPR2). Yet carriers have only a 20% risk of disease, suggesting that other factors influence penetrance. Thrombospondin-1 (TSP1) regulates activation of TGF-β and inhibits endothelial and smooth muscle cell proliferation, pathways coincidentally altered in pulmonary arterial hypertension (PAH). To determine whether a subset of FPAH patients also have mutations in the TSP1 gene (THBS1) we resequenced the type I repeats of THBS1 encoding the TGF-β regulation and cell growth inhibition domains in 60 FPAH probands, 70 nonfamilial PAH subjects, and in large control groups. We identified THBS1 mutations in three families: a novel missense mutation in two (Asp362Asn), and an intronic mutation in a third (IVS8+255 G/A). Neither mutation was detected in population controls. Mutant 362Asn TSP1 had less than half of the ability of wild-type TSP1 to activate TGF-β. Mutant 362Asn TSP1 also lost the ability to inhibit growth of pulmonary arterial smooth muscle cells and was over threefold less effective at inhibiting endothelial cell growth. The IVS8+255 G/A mutation decreased and/or eliminated local binding of the transcription factors SP1 and MAZ but did not affect RNA splicing. These novel mutations implicate THBS1 as a modifier gene in FPAH. These THBS1 mutations have implications in the genetic evaluation of FPAH patients. However, since FPAH is rare, these data are most relevant as evidence for the importance of TSP1 in pulmonary vascular homeostasis. Further examination of THBS1 in the pathogenesis of PAH is warranted. PMID:22198906

Mesenchymal stem cells and differentiated insulin producing cells are new horizons for pancreatic regeneration in type I diabetes mellitus.

PubMed

Domouky, Ayat M; Hegab, Ashraf S; Al-Shahat, Amal; Raafat, Nermin

2017-06-01

Diabetes mellitus has become the third human killer following cancer and cardiovascular disease. Millions of patients, often children, suffer from type 1 diabetes (T1D). Stem cells created hopes to regenerate damaged body tissues and restore their function. This work aimed at clarifying and comparing the therapeutic potential of differentiated and non-differentiated mesenchymal stem cells (MSCs) as a new line of therapy for T1D. 40 Female albino rats divided into group I (control): 10 rats and group II (diabetic), III and IV, 10 rats in each, were injected with streptozotocin (50mg/kg body weight). Group III (MSCs) were transplanted with bone marrow derived MSCs from male rats and group IV (IPCs) with differentiated insulin producing cells. Blood and pancreatic tissue samples were taken from all rats for biochemical and histological studies. MSCs reduced hyperglycemia in diabetic rats on day 15 while IPCs normalizes blood glucose level on day 7. Histological and morphometric analysis of pancreas of experimental diabetic rats showed improvement in MSCs-treated group but in IPCs-treated group, β-cells insulin immunoreactions were obviously returned to normal, with normal distribution of β-cells in the center and other cells at the periphery. Meanwhile, most of the pathological lesions were still detected in diabetic rats. MSCs transplantation can reduce blood glucose level in recipient diabetic rats. IPCs initiate endogenous pancreatic regeneration by neogenesis of islets. IPCs are better than MSCs in regeneration of β-cells. So, IPCs therapy can be considered clinically to offer a hope for patients suffering from T1D. Copyright © 2017 Elsevier Ltd. All rights reserved.

Altered thermogenesis and impaired bone remodeling in Misty mice.

PubMed

Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E; Bornstein, Sheila A; Le, Phuong; Kawai, Masanobu; Lotinun, Sutada; Horowitz, Mark C; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2013-09-01

Fat mass may be modulated by the number of brown-like adipocytes in white adipose tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic energy metabolism and, with age, bone remodeling becomes uncoupled and brown adipose tissue (BAT) function declines. To test the interaction between BAT and bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We found that Misty mice have accelerated age-related trabecular bone loss and impaired brown fat function (including reduced temperature, lower expression of Pgc1a, and less sympathetic innervation compared to wild-type (+/ +)). Despite reduced BAT function, Misty mice had normal core body temperature, suggesting heat is produced from other sources. Indeed, upon acute cold exposure (4°C for 6 hours), inguinal WAT from Misty mice compensated for BAT dysfunction by increasing expression of Acadl, Pgc1a, Dio2, and other thermogenic genes. Interestingly, acute cold exposure also decreased Runx2 and increased Rankl expression in Misty bone, but only Runx2 was decreased in wild-type. Browning of WAT is under the control of the sympathetic nervous system (SNS) and, if present at room temperature, could impact bone metabolism. To test whether SNS activity could be responsible for accelerated trabecular bone loss, we treated wild-type and Misty mice with the β-blocker, propranolol. As predicted, propranolol slowed trabecular bone volume/total volume (BV/TV) loss in the distal femur of Misty mice without affecting wild-type. Finally, the Misty mutation (a truncation of DOCK7) also has a significant cell-autonomous role. We found DOCK7 expression in whole bone and osteoblasts. Primary osteoblast differentiation from Misty calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling. Despite the multifaceted effects of the Misty mutation, we have shown that impaired brown fat function leads to altered SNS activity and bone loss, and for the first time that cold exposure negatively affects bone remodeling. Copyright © 2013 American Society for Bone and Mineral Research.

Massage Therapy Given by Caregiver in Treating Quality of Life of Young Patients Undergoing Treatment for Cancer

ClinicalTrials.gov

2018-05-24

Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Noncontiguous Stage II Mantle Cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Accelerated Return to Sport After Anterior Cruciate Ligament Reconstruction and Early Knee Osteoarthritis Features at 1 Year: An Exploratory Study.

PubMed

Culvenor, Adam G; Patterson, Brooke E; Guermazi, Ali; Morris, Hayden G; Whitehead, Timothy S; Crossley, Kay M

2018-04-01

A timely return to competitive sport is a primary goal of anterior cruciate ligament reconstruction (ACLR). It is not known whether an accelerated return to sport increases the risk of early-onset knee osteoarthritis (KOA). To determine whether an accelerated return to sport post-ACLR (ie, <10 months) is associated with increased odds of early KOA features on magnetic resonance imaging (MRI) 1 year after surgery and to evaluate the relationship between an accelerated return to sport and early KOA features stratified by type of ACL injury (isolated or concurrent chondral/meniscal injury) and lower limb function (good or poor). Cross-sectional study. Private radiology clinic and university laboratory. A total of 111 participants (71 male; mean age 30 ± 8 years) 1-year post-ACLR. Participants completed a self-report questionnaire regarding postoperative return-to-sport data (specific sport, postoperative month first returned), and isotropic 3-T MRI scans were obtained. Early KOA features (bone marrow, cartilage and meniscal lesions, and osteophytes) assessed with the MRI OA Knee Score. Logistic regression analyses evaluated the odds of early KOA features with an accelerated return to sport (<10 months post-ACLR versus ≥10 months or no return to sport) in the total cohort and stratified by type of ACL injury and lower limb function. Forty-six (41%) participants returned to competitive sport <10 months post-ACLR. An early return to sport was associated with significantly increased odds of bone marrow lesions (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3-6.0) but not cartilage (OR 1.2, 95% CI 0.5-2.6) or meniscal lesions (OR 0.8, 95% CI 0.4-1.8) or osteophytes (OR 0.6, 95% CI 0.3-1.4). In those with poor lower limb function, early return to sport exacerbated the odds of bone marrow lesions (OR 4.6, 95% CI 1.6-13.5), whereas stratified analyses for type of ACL injury did not reach statistical significance. An accelerated return to sport, particularly in the presence of poor lower limb function, may be implicated in posttraumatic KOA development. IV. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Discovery of Novel Drugs to Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis

DTIC Science & Technology

2015-08-01

AWARD NUMBER: W81XWH-13-1-0113 TITLE: Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin...Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis 5a...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Patients with Neurofibromatosis (NF1

Native structure of a type IV secretion system core complex essential for Legionella pathogenesis.

PubMed

Kubori, Tomoko; Koike, Masafumi; Bui, Xuan Thanh; Higaki, Saori; Aizawa, Shin-Ichi; Nagai, Hiroki

2014-08-12

Bacterial type IV secretion systems are evolutionarily related to conjugation systems and play a pivotal role in infection by delivering numerous virulence factors into host cells. Using transmission electron microscopy, we report the native molecular structure of the core complex of the Dot/Icm type IV secretion system encoded by Legionella pneumophila, an intracellular human pathogen. The biochemically isolated core complex, composed of at least five proteins--DotC, DotD, DotF, DotG, and DotH--has a ring-shaped structure. Intriguingly, morphologically distinct premature complexes are formed in the absence of DotG or DotF. Our data suggest that DotG forms a central channel spanning inner and outer membranes. DotF, a component dispensable for type IV secretion, plays a role in efficient embedment of DotG into the functional core complex. These results highlight a common scheme for the biogenesis of transport machinery.

Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker.

PubMed

Tanko, Zita; Shab, Arna; Diepgen, Thomas Ludwig; Weisshaar, Elke

2009-06-01

Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.

Melorheostosis may originate as a type 2 segmental manifestation of osteopoikilosis.

PubMed

Happle, Rudolf

2004-03-15

Melorheostosis is a non-hereditary disorder involving the bones in a segmental pattern, whereas osteopoikilosis is a rather mild disseminated bone disorder inherited as an autosomal dominant trait. Interestingly, melorheostosis and osteopoikilosis may sometimes occur together. In analogy to various autosomal dominant skin disorders for which a type 2 segmental manifestation has been postulated, melorheostosis may be best explained in such cases as a type 2 segmental osteopoikilosis, resulting from early loss of the corresponding wild type allele at the gene locus of this autosomal dominant bone disorder. Copyright 2003 Wiley-Liss, Inc.

Velocities of Bone Mineral Accrual in Black and White American Children

PubMed Central

Hui, Siu L; Perkins, Anthony J; Harezlak, Jaroslaw; Peacock, Munro; McClintock, Cindy L; Johnston, C Conrad

2010-01-01

Black adults have higher bone mass than whites in the United States, but it is not clear when black children gain bone mineral faster than white children. We performed a cohort study to compare the growth velocity of total-body bone mineral content (TBMC) between black and white children of the same sex at different ages and stages of sexual maturity. TBMC and total-body area were measured in a cohort of 188 black and white boys and girls aged 5 to 15 years annually for up to 4 years. Rates of change in TBMC and area were found to vary with age and with Tanner stage. For both TBMC and area, growth velocities between black and white children differed significantly across Tanner stages. Age-specific velocities were higher in black children during prepuberty and initial entry into puberty but reversed in subsequent Tanner stages. Despite earlier entry into each Tanner stage, black children spent only an average of only 0.2 year longer in Tanner stages II through IV, and total gain in TBMC from age 5 to 15 was not higher in whites. In conclusion, the higher bone mass in black adults compared with whites cannot be attributed to faster accrual during puberty. It is due to black children's higher rate of bone mineral accrual in prepuberty and plausibly in postpuberty. Most of the racial difference in TBMC velocity can be explained by growth in size. © 2010 American Society for Bone and Mineral Research. PMID:20200959

Bone augmentation at peri-implant dehiscence defects comparing a synthetic polyethylene glycol hydrogel matrix vs. standard guided bone regeneration techniques.

PubMed

Thoma, Daniel S; Jung, Ui-Won; Park, Jin-Young; Bienz, Stefan P; Hüsler, Jürg; Jung, Ronald E

2017-07-01

The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/TCP mixed with a synthetic PEG hydrogel, ii)HA/TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/TCP covered with a native collagen membrane (CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro-CT and histological analyses were performed. Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Co-culture of osteocytes and neurons on a unique patterned surface.

PubMed

Boggs, Mary E; Thompson, William R; Farach-Carson, Mary C; Duncan, Randall L; Beebe, Thomas P

2011-12-01

Neural and skeletal communication is essential for the maintenance of bone mass and transmission of pain, yet the mechanism(s) of signal transduction between these tissues is unknown. The authors established a novel system to co-culture murine long bone osteocyte-like cells (MLO-Y4) and primary murine dorsal root ganglia (DRG) neurons. Assessment of morphology and maturation marker expression on perlecan domain IV peptide (PlnDIV) and collagen type-1 (Col1) demonstrated that PlnDIV was an optimal matrix for MLO-Y4 culture. A novel matrix-specificity competition assay was developed to expose these cells to several extracellular matrix proteins such as PlnDIV, Col1, and laminin (Ln). The competition assay showed that approximately 70% of MLO-Y4 cells preferred either PlnDIV or Col1 to Ln. To co-culture MLO-Y4 and DRG, we developed patterned surfaces using micro-contact printing to create 40 μm × 1 cm alternating stripes of PlnDIV and Ln or PlnDIV and Col1. Co-culture on PlnDIV/Ln surfaces demonstrated that these matrix molecules provided unique cues for each cell type, with MLO-Y4 preferentially attaching to the PlnDIV lanes and DRG neurons to the Ln lanes. Approximately 80% of DRG were localized to Ln. Cellular processes from MLO-Y4 were closely associated with axonal extensions of DRG neurons. Approximately 57% of neuronal processes were in close proximity to nearby MLO-Y4 cells at the PlnDIV-Ln interface. The surfaces in this new assay provided a unique model system with which to study the communication between osteocyte-like cells and neurons in an in vitro environment.

Bone mineralization and vascularization in bisphosphonate-related osteonecrosis of the jaw: an experimental study in the rat.

PubMed

Kün-Darbois, Jean-Daniel; Libouban, Hélène; Mabilleau, Guillaume; Pascaretti-Grizon, Florence; Chappard, Daniel

2018-02-16

Pathogenesis of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is not fully explained. An antiangiogenic effect of bisphosphonates (BPs) or an altered bone quality have been advocated. The aims of the present study were to analyze alveolar mandibular vascularization and bone quality in rats with BRONJ. Thirty-eight Sprague-Dawley rats were randomized into two groups: zoledronic acid (ZA), n = 27, and control (CTRL) n = 11. The ZA group received a weekly IV injection of ZA (100 μg/kg) during 10 weeks. The CTRL group received saline. After 6 weeks, extraction of the right mandibular molars was performed. Rats were sacrificed after 14 weeks. Microtomography characterized bone lesions and vascularization after injection of a radio-opaque material. Raman microspectroscopy evaluated bone mineralization. Fifty-five percent of ZA rats presented bone exposure and signs of BRONJ. None sign was found at the left hemimandible in the ZA group and in the CTRL group. Vascular density appeared significantly increased in the right hemimandibles of the CTRL group compared to the left hemimandibles. Vascularization was reduced in the ZA group. A significantly increased of the mineral-to-amide ratio was found in the alveolar bone of ZA rats by Raman microspectroscopy. In a rat model of BRONJ, microtomography evidenced osteonecrosis in BRONJ. Raman spectroscopy showed an increased mineralization. Vascularization after tooth extraction was impaired by ZA. Prolonged BP administration caused an increase in the mineralization and a quantitative reduction of the vascularization in the alveolar bone; both factors might be involved concomitantly in the BRONJ pathophysiology.

Crystal Structure of the Minor Pilin CofB, the Initiator of CFA/III Pilus Assembly in Enterotoxigenic Escherichia coli*

PubMed Central

Kolappan, Subramania; Ng, Dixon; Yang, Guixiang; Harn, Tony; Craig, Lisa

2015-01-01

Type IV pili are extracellular polymers of the major pilin subunit. These subunits are held together in the pilus filament by hydrophobic interactions among their N-terminal α-helices, which also anchor the pilin subunits in the inner membrane prior to pilus assembly. Type IV pilus assembly involves a conserved group of proteins that span the envelope of Gram-negative bacteria. Among these is a set of minor pilins, so named because they share their hydrophobic N-terminal polymerization/membrane anchor segment with the major pilins but are much less abundant. Minor pilins influence pilus assembly and retraction, but their precise functions are not well defined. The Type IV pilus systems of enterotoxigenic Escherichia coli and Vibrio cholerae are among the simplest of Type IV pilus systems and possess only a single minor pilin. Here we show that the enterotoxigenic E. coli minor pilins CofB and LngB are required for assembly of their respective Type IV pili, CFA/III and Longus. Low levels of the minor pilins are optimal for pilus assembly, and CofB can be detected in the pilus fraction. We solved the 2.0 Å crystal structure of N-terminally truncated CofB, revealing a pilin-like protein with an extended C-terminal region composed of two discrete domains connected by flexible linkers. The C-terminal region is required for CofB to initiate pilus assembly. We propose a model for CofB-initiated pilus assembly with implications for understanding filament growth in more complex Type IV pilus systems as well as the related Type II secretion system. PMID:26324721

Crystal Structure of the Minor Pilin CofB, the Initiator of CFA/III Pilus Assembly in Enterotoxigenic Escherichia coli.

PubMed

Kolappan, Subramania; Ng, Dixon; Yang, Guixiang; Harn, Tony; Craig, Lisa

2015-10-23

Type IV pili are extracellular polymers of the major pilin subunit. These subunits are held together in the pilus filament by hydrophobic interactions among their N-terminal α-helices, which also anchor the pilin subunits in the inner membrane prior to pilus assembly. Type IV pilus assembly involves a conserved group of proteins that span the envelope of Gram-negative bacteria. Among these is a set of minor pilins, so named because they share their hydrophobic N-terminal polymerization/membrane anchor segment with the major pilins but are much less abundant. Minor pilins influence pilus assembly and retraction, but their precise functions are not well defined. The Type IV pilus systems of enterotoxigenic Escherichia coli and Vibrio cholerae are among the simplest of Type IV pilus systems and possess only a single minor pilin. Here we show that the enterotoxigenic E. coli minor pilins CofB and LngB are required for assembly of their respective Type IV pili, CFA/III and Longus. Low levels of the minor pilins are optimal for pilus assembly, and CofB can be detected in the pilus fraction. We solved the 2.0 Å crystal structure of N-terminally truncated CofB, revealing a pilin-like protein with an extended C-terminal region composed of two discrete domains connected by flexible linkers. The C-terminal region is required for CofB to initiate pilus assembly. We propose a model for CofB-initiated pilus assembly with implications for understanding filament growth in more complex Type IV pilus systems as well as the related Type II secretion system. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Aluminum, iron, lead, cadmium, copper, zinc, chromium, magnesium, strontium, and calcium content in bone of end-stage renal failure patients.

PubMed

D'Haese, P C; Couttenye, M M; Lamberts, L V; Elseviers, M M; Goodman, W G; Schrooten, I; Cabrera, W E; De Broe, M E

1999-09-01

Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease. We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry. The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients' gender. The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.

Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fractures: Analysis of Risk Factors.

PubMed

Xie, Weixing; Jin, Daxiang; Ma, Hui; Ding, Jinyong; Xu, Jixi; Zhang, Shuncong; Liang, De

2016-05-01

The risk factors for cement leakage were retrospectively reviewed in 192 patients who underwent percutaneous vertebral augmentation (PVA). To discuss the factors related to the cement leakage in PVA procedure for the treatment of osteoporotic vertebral compression fractures. PVA is widely applied for the treatment of osteoporotic vertebral fractures. Cement leakage is a major complication of this procedure. The risk factors for cement leakage were controversial. A retrospective review of 192 patients who underwent PVA was conducted. The following data were recorded: age, sex, bone density, number of fractured vertebrae before surgery, number of treated vertebrae, severity of the treated vertebrae, operative approach, volume of injected bone cement, preoperative vertebral compression ratio, preoperative local kyphosis angle, intraosseous clefts, preoperative vertebral cortical bone defect, and ratio and type of cement leakage. To study the correlation between each factor and cement leakage ratio, bivariate regression analysis was employed to perform univariate analysis, whereas multivariate linear regression analysis was employed to perform multivariate analysis. The study included 192 patients (282 treated vertebrae), and cement leakage occurred in 100 vertebrae (35.46%). The vertebrae with preoperative cortical bone defects generally exhibited higher cement leakage ratio, and the leakage is typically type C. Vertebrae with intact cortical bones before the procedure tend to experience type S leakage. Univariate analysis showed that patient age, bone density, number of fractured vertebrae before surgery, and vertebral cortical bone were associated with cement leakage ratio (P<0.05). Multivariate analysis showed that the main factors influencing bone cement leakage are bone density and vertebral cortical bone defect, with standardized partial regression coefficients of -0.085 and 0.144, respectively. High bone density and vertebral cortical bone defect are independent risk factors associated with bone cement leakage.

Expression profiling of microRNAs in human bone tissue from postmenopausal women.

PubMed

De-Ugarte, Laura; Serra-Vinardell, Jenny; Nonell, Lara; Balcells, Susana; Arnal, Magdalena; Nogues, Xavier; Mellibovsky, Leonardo; Grinberg, Daniel; Diez-Perez, Adolfo; Garcia-Giralt, Natalia

2018-01-01

Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5). MicroRNA expression profiling was obtained for each sample by microarray and a global miRNA analysis was performed combining the data acquired in all the microarray experiments. From the 641 miRNAs detected in bone tissue samples, 346 (54%) were present in osteoblasts and/or osteoclasts. The other 46% were not identified in any of the bone cells analyzed. Intersection of osteoblast and osteoclast arrays identified 101 miRNAs shared by both cell types, which accounts for 30-40% of miRNAs detected in these cells. In osteoblasts, 266 miRNAs were detected, of which 243 (91%) were also present in the total bone array, representing 38% of all bone miRNAs. In osteoclasts, 340 miRNAs were detected, of which 196 (58%) were also present in the bone tissue array, representing 31% of all miRNAs detected in total bone. These analyses provide an overview of miRNAs expressed in bone tissue, broadening our knowledge in the microRNA field.

The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

PubMed Central

Boucharaba, Ahmed; Serre, Claire-Marie; Guglielmi, Julien; Bordet, Jean-Claude; Clézardin, Philippe; Peyruchaud, Olivier

2006-01-01

Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA1) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA1 using a pharmacological antagonist mimics the effects of silencing LPA1 in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA1 expressed by tumor cells may be a promising therapeutic target for patients with bone metastases. PMID:16769891

Biomechanical competence of six different bone screws for reconstructive surgery in three different transplants: Fibular, iliac crest, scapular and artificial bone.

PubMed

Pietsch, Arnold P; Raith, Stefan; Ode, Jan-Eric; Teichmann, Jan; Lethaus, Bernd; Möhlhenrich, Stephan C; Hölzle, Frank; Duda, Georg N; Steiner, Timm

2016-06-01

The goal of this study was to determine a combination of screw and transplantation type that offers optimal primary stability for reconstructive surgery. Fibular, iliac crest, and scapular transplants were tested along with artificial bone substrate. Six different kinds of bone screws (Medartis(©)) were compared, each type utilized with one of six specimens from human transplants (n = 6). Controlled screw-in-tests were performed and the required torque was protocolled. Subsequently, pull-out-tests were executed to determine the retention forces. The artificial bone substitute material showed significantly higher retention forces than real bone samples. The self-drilling screws achieved the significantly highest retention values in the synthetic bone substitute material. Cancellous screws achieved the highest retention in the fibular transplants, while self-drilling and cancellous screws demonstrated better retention than cortical screws in the iliac crest. In the scapular graft, no significant differences were found between the screw types. In comparison to the human transplant types, the cortical screws showed the significantly highest values in the fibula and the lowest values in the iliac crest. The best retention was found in the combination of cancellous screws with fibular graft (514.8 N + -252.3 N). For the flat bones (i.e., scapular and illiac crest) we recommend the cancellous screws. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Transient chondrogenic phase in the intramembranous pathway during normal skeletal development.

PubMed

Nah, H D; Pacifici, M; Gerstenfeld, L C; Adams, S L; Kirsch, T

2000-03-01

Calvarial and facial bones form by intramembranous ossification, in which bone cells arise directly from mesenchyme without an intermediate cartilage anlage. However, a number of studies have reported the emergence of chondrocytes from in vitro calvarial cell or organ cultures and the expression of type II collagen, a cartilage-characteristic marker, in developing calvarial bones. Based on these findings we hypothesized that a covert chondrogenic phase may be an integral part of the normal intramembranous pathway. To test this hypothesis, we analyzed the temporal and spatial expression patterns of cartilage characteristic genes in normal membranous bones from chick embryos at various developmental stages (days 12, 15 and 19). Northern and RNAse protection analyses revealed that embryonic frontal bones expressed not only the type I collagen gene but also a subset of cartilage characteristic genes, types IIA and XI collagen and aggrecan, thus resembling a phenotype of prechondrogenic-condensing mesenchyme. The expression of cartilage-characteristic genes decreased with the progression of bone maturation. Immunohistochemical analyses of developing embryonic chick heads indicated that type II collagen and aggrecan were produced by alkaline phosphatase activity positive cells engaged in early stages of osteogenic differentiation, such as cells in preosteogenic-condensing mesenchyme, the cambium layer of periosteum, the advancing osteogenic front, and osteoid bone. Type IIB and X collagen messenger RNAs (mRNA), markers for mature chondrocytes, were also detected at low levels in calvarial bone but not until late embryonic stages (day 19), indicating that some calvarial cells may undergo overt chondrogenesis. On the basis of our findings, we propose that the normal intramembranous pathway in chicks includes a previously unrecognized transient chondrogenic phase similar to prechondrogenic mesenchyme, and that the cells in this phase retain chondrogenic potential that can be expressed in specific in vitro and in vivo microenvironments.

Pharmacokinetics, Distribution, Metabolism, and Excretion of Omadacycline following a Single Intravenous or Oral Dose of 14C-Omadacycline in Rats

PubMed Central

Lin, Wen; Flarakos, Jimmy; Du, Yancy; Hu, Wenyu; He, Handan; Mangold, James; Tanaka, S. Ken

2016-01-01

ABSTRACT The absorption, distribution, metabolism, and excretion (ADME) of omadacycline, a first-in-class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, were evaluated in rats. Tissue distribution was investigated by quantitative whole-body autoradiography in male Long-Evans Hooded (LEH) rats. Following an intravenous (i.v.) dose of 5 mg/kg of body weight, radioactivity widely and rapidly distributed into most tissues. The highest tissue-to-blood concentration ratios (t/b) were observed in bone mineral, thyroid gland, and Harderian gland at 24 h post-i.v. dose. There was no evidence of stable accumulation in uveal tract tissue, suggesting the absence of a stable binding interaction with melanin. Following a 90 mg/kg oral dose in LEH rats, the highest t/b were observed in bone mineral, Harderian gland, liver, spleen, and salivary gland. The plasma protein binding levels were 26% in the rat and 15% to 21% in other species. Omadacycline plasma clearance was 1.2 liters/h/kg, and its half-life was 4.6 h; the steady-state volume of distribution (Vss) was 6.89 liters/kg. Major circulating components in plasma were intact omadacycline and its epimer. Consistent with observations in human, approximately 80% of the dose was excreted into the feces as unchanged omadacycline after i.v. administration. Fecal excretion was primarily the result of biliary excretion (∼40%) and direct gastrointestinal secretion (∼30%). However, urinary excretion (∼30%) was equally prominent after i.v. dosing. PMID:27821446

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flandin, Isabelle; Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon; Hartmann, Olivier

2006-04-01

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver,more » kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.« less

An open cohort study of bone metastasis incidence following surgery in breast cancer patients.

PubMed

Koizumi, Mitsuru; Yoshimoto, Masataka; Kasumi, Fujio; Iwase, Takuji

2010-07-21

To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate. Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients) were followed up regarding bone metastasis until December 2006. Patients' characteristics at the time of surgery were analyzed by Cox's method, with bone metastasis as events. Patient groups were assigned according to Cox's analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year), medium risk (1-3%), and low risk (<1%). Bone metastasis incidence was constant between 1.0 and 2.8% per person-year more than 10 years. Non-invasive cancer was associated with a very low incidence of bone metastasis (1/436). Multivariate Cox's analysis indicated important factors for bone metastasis were tumor grade (T), nodal grade (pN), and histology. Because T and pN were important factors for bone metastasis prediction, subgroups were made by pTNM stage. Patients at stages IIIA, IIIB and IV had an incidence of >3% per person-year, patients with stage I <1% per person-year, and those with stages II were between 1 and 3%. Further analysis with histology in stage II patients showed that stage IIB with high risk histology also had a high incidence (3% person year), whereas stage IIA with medium risk histology were <1%. Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups.

The effect of different concentrations of topical ozone administration on bone formation in orthopedically expanded suture in rats

PubMed Central

Ramoglu, Sabri Ilhan; Sonmez, Mehmet Fatih

2016-01-01

Summary Background/objective: The aim of this study was to investigate the effects of different concentrations of ozone (O3) therapy on bone regeneration in response to an expansion of the inter-premaxillary suture in rats. Materials and methods: Forty-eight Wistar rats were randomly divided into four groups (n = 12). In groups I, II, and III, 1ml of O3 at 10, 25, and 40 µg/ml was injected at the premaxillary suture, respectively. In group IV (control group), 1ml of saline solution was injected at the same point during the expansion procedure for 5 days. Bone regeneration in the suture was evaluated histomorphometrically. The area of new bone and fibrotic area, the number of osteoblasts and osteoclasts, and the amount of vascularity were measured and compared. The density of the newly formed bone in the expansion area was measured by using cone beam computed tomography. Data were analyzed using the Kruskal–Wallis one-way analysis of variance and post hoc Student-Newman–Keuls tests. Results: New bone area, fibrotic area, osteoblast and osteoclast numbers, and the amount of vascularity were significantly higher in experimental groups compared with the control group (P < 0.001). The density of newly formed bone (P < 0.001), new bone formation (P = 0.009), number of capillaries (P < 0.001), number of osteoclasts (P = 0.016), and number of osteoblasts (P < 0.001) in the maxillary sutures were highest in the 25 μg/ml O3 group compared with the other experimental groups and control group. Conclusions/implications: The application of O3 therapy can stimulate bone regeneration in an orthopedically expanded inter-premaxillary suture during both the expansion and retention periods. PMID:26136437

Prediction of autosomal STR typing success in ancient and Second World War bone samples.

PubMed

Zupanič Pajnič, Irena; Zupanc, Tomaž; Balažic, Jože; Geršak, Živa Miriam; Stojković, Oliver; Skadrić, Ivan; Črešnar, Matija

2017-03-01

Human-specific quantitative PCR (qPCR) has been developed for forensic use in the last 10 years and is the preferred DNA quantification technique since it is very accurate, sensitive, objective, time-effective and automatable. The amount of information that can be gleaned from a single quantification reaction using commercially available quantification kits has increased from the quantity of nuclear DNA to the amount of male DNA, presence of inhibitors and, most recently, to the degree of DNA degradation. In skeletal remains samples from disaster victims, missing persons and war conflict victims, the DNA is usually degraded. Therefore the new commercial qPCR kits able to assess the degree of degradation are potentially able to predict the success of downstream short tandem repeat (STR) typing. The goal of this study was to verify the quantification step using the PowerQuant kit with regard to its suitability as a screening method for autosomal STR typing success on ancient and Second World War (WWII) skeletal remains. We analysed 60 skeletons excavated from five archaeological sites and four WWII mass graves from Slovenia. The bones were cleaned, surface contamination was removed and the bones ground to a powder. Genomic DNA was obtained from 0.5g of bone powder after total demineralization. The DNA was purified using a Biorobot EZ1 device. Following PowerQuant quantification, DNA samples were subjected to autosomal STR amplification using the NGM kit. Up to 2.51ng DNA/g of powder were extracted. No inhibition was detected in any of bones analysed. 82% of the WWII bones gave full profiles while 73% of the ancient bones gave profiles not suitable for interpretation. Four bone extracts yielded no detectable amplification or zero quantification results and no profiles were obtained from any of them. Full or useful partial profiles were produced only from bone extracts where short autosomal (Auto) and long degradation (Deg) PowerQuant targets were detected. It is concluded that STR typing of old bones after quantification with the PowerQuant should be performed only when both Auto and Deg targets are detected simultaneously with no respect to [Auto]/[Deg] ratio. Prediction of STR typing success could be made according to successful amplification of Deg fragment. The PowerQuant kit is capable of identifying bone DNA samples that will not yield useful STR profiles using the NGM kit, and it can be used as a predictor of autosomal STR typing success of bone extracts obtained from ancient and WWII skeletal remains. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The efficacy of the use of IR laser phototherapy associated to biphasic ceramic graft and guided bone regeneration on surgical fractures treated with miniplates: a histological and histomorphometric study on rabbits.

PubMed

Pinheiro, Antonio L B; Aciole, Gilberth Tadeu Santos; Ramos, Thais Andrade; Gonzalez, Tayná Assunção; da Silva, Laís Nogueira; Soares, Luiz G Pinheiro; Aciole, Jouber Mateus Santos; dos Santos, Jean Nunes

2014-01-01

The aim of the present study was to assess, by light microscopy and histomorphometry, the repair of surgical fractures fixed with internal rigid fixation (IRF) treated or not with IR laser (λ780 nm, 50 mW, 4 × 4 J/cm(2) = 16 J/cm(2), ϕ = 0.5 cm(2), CW) associated or not to the use of hydroxyapatite and guided bone regeneration. Surgical tibial fractures were created under general anesthesia on 15 rabbits that were divided into 5 groups, maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet, and had water ad libidum. The fractures in groups II, III, IV, and V were fixed with miniplates. Animals in groups III and V were grafted with hydroxyapatite and GBR technique used. Animals in groups IV and V were irradiated at every other day during two weeks (4 × 4 J/cm(2), 16 J/cm(2) = 112 J/cm(2)). Observation time was that of 30 days. After animal death, specimens were taken, routinely processed to wax, cut and stained with HA and Sirius red, and used for histological assessment. The results of both analyses showed a better bone repair on all irradiated subjects especially when the biomaterial and GBR were used. In conclusion, the results of the present investigation are important clinically as they are suggestive that the association of hydroxyapatite, and laser light resulted in a positive and significant repair of complete tibial fractures treated with miniplates.

Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis

PubMed Central

Yang, Y.; Lin, S.; Wang, B.; Gu, W.

2017-01-01

Objectives Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023. PMID:28634158

Spatial and Functional Relationships Among Pol V-Associated loci, Pol IV-Dependent siRNAs, and Cytosine Methylation in the Arabidopsis Epigenome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wierzbicki, A. T.; Cocklin, Ross; Mayampurath, Anoop

2012-08-15

Multisubunit RNA polymerases IV and V (Pols IV and V) mediate RNA-directed DNA methylation and transcriptional silencing of retrotransposons and heterochromatic repeats in plants. We identified genomic sites of Pol V occupancy in parallel with siRNA deep sequencing and methylcytosine mapping, comparing wild-type plants with mutants defective for Pol IV, Pol V, or both Pols IV and V. Approximately 60% of Pol V-associated regions encompass regions of 24-nucleotide (nt) siRNA complementarity and cytosine methylation, consistent with cytosine methylation being guided by base-pairing of Pol IV-dependent siRNAs with Pol V transcripts. However, 27% of Pol V peaks do not overlap sitesmore » of 24-nt siRNA biogenesis or cytosine methylation, indicating that Pol V alone does not specify sites of cytosine methylation. Surprisingly, the number of methylated CHH motifs, a hallmark of RNA-directed de novo methylation, is similar in wild-type plants and Pol IV or Pol V mutants. In the mutants, methylation is lost at 50%-60% of the CHH sites that are methylated in the wild type but is gained at new CHH positions, primarily in pericentromeric regions. These results indicate that Pol IV and Pol V are not required for cytosine methyltransferase activity but shape the epigenome by guiding CHH methylation to specific genomic sites.« less

Correlation of mandibular impacted tooth and bone morphology determined by cone beam computed topography on a premise of third molar operation.

PubMed

Momin, M A; Matsumoto, K; Ejima, K; Asaumi, R; Kawai, T; Arai, Y; Honda, K; Yosue, T

2013-05-01

To determine the width and morphology of the mandible in the impacted third molar region, and to identify the location of the mandibular canal prior to planning impacted third molar operations. Cone beam computed tomography (CBCT) data of 87 mandibular third molars from 62 Japanese patients were analyzed in this study. The width of the lingual cortical bone and apex-canal distance were measured from cross-sectional images in which the cortical bone was thinnest at the lingual side in the third molar region. Images were used for measuring the space (distance between the inner border of the lingual cortical bone and outer surface of the third molar root), apex-canal distance (distance from the root of the third molar tooth to the superior border of the inferior alveolar canal) and the cortical bone (width between the inner and outer borders of the lingual cortical bone). The means of the space, apex-canal distance and lingual cortical width were 0.31, 1.99, and 0.68 mm, respectively. Impacted third molar teeth (types A-C) were observed at the following frequencies: type A (angular) 37 %; type B (horizontal), 42 %; type C (vertical), 21 %. The morphology of the mandible at the third molar region (types D-F) was observed as: type D (round), 49 %; type E (lingual extended), 18 %; and type F (lingual concave), 32 %. The width and morphology of the mandible with impacted teeth and the location of the mandibular canal at the third molar region could be clearly determined using cross-sectional CBCT images.

The Effects of Androgens on Murine Cortical Bone Do Not Require AR or ERα Signaling in Osteoblasts and Osteoclasts

PubMed Central

Ucer, Serra; Iyer, Srividhya; Bartell, Shoshana M; Martin-Millan, Marta; Han, Li; Kim, Ha-Neui; Weinstein, Robert S; Jilka, Robert L; O’Brien, Charles A; Almeida, Maria; Manolagas, Stavros C

2016-01-01

In men, androgens are critical for the acquisition and maintenance of bone mass in both the cortical and cancellous bone compartment. Male mice with targeted deletion of the androgen receptor (AR) in mature osteoblasts or osteocytes have lower cancellous bone mass, but no cortical bone phenotype. We have investigated the possibility that the effects of androgens on the cortical compartment result from AR signaling in osteoprogenitors or cells of the osteoclast lineage; or via estrogen receptor alpha (ERα) signaling in either or both of these two cell types upon conversion of testosterone to estradiol. To this end, we generated mice with targeted deletion of an AR or an ERα allele in the mesenchymal (ARf/y;Prx1-Cre or ERαf/f;Osx1-Cre) or myeloid cell lineage (ARf/y; LysM-Cre or ERαf/f;LysM-Cre) and their descendants. Male ARf/y;Prx1-Cre mice exhibited decreased bone volume and trabecular number, and increased osteoclast number in the cancellous compartment. Moreover, they did not undergo the loss of cancellous bone volume and trabecular number caused by orchidectomy (ORX) in their littermate controls. In contrast, ARf/y;LysM-Cre, ERαf/f; Osx1-Cre, or ERαf/f;LysM-Cre mice had no cancellous bone phenotype at baseline and lost the same amount of cancellous bone as their controls following ORX. Most unexpectedly, adult males of all four models had no discernible cortical bone phenotype at baseline, and lost the same amount of cortical bone as their littermate controls after ORX. Recapitulation of the effects of ORX by AR deletion only in the ARf/y;Prx1-Cre mice indicates that the effects of androgens on cancellous bone result from AR signaling in osteoblasts—not on osteoclasts or via aromatization. The effects of androgens on cortical bone mass, on the other hand, do not require AR or ERα signaling in any cell type across the osteoblast or osteoclast differentiation lineage. Therefore, androgens must exert their effects indirectly by actions on some other cell type(s) or tissue(s). PMID:25704845

Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study

PubMed Central

Zhou, Hua; Recker, Robert R.; Brown, Jacques P.; Recknor, Christopher P.; Lewiecki, E. Michael; Miller, Paul D.; Rao, Sudhaker D.; Kendler, David L.; Lindsay, Robert; Krege, John H.; Alam, Jahangir; Taylor, Kathleen A.; Janos, Boris; Ruff, Valerie A.

2016-01-01

Context: Denosumab-induced PTH elevation may stimulate early bone formation. Objective: Our objective was to evaluate whether denosumab-induced changes of intact PTH (iPTH) result in early anabolic effects according to histomorphometry and bone turnover markers (BTMs) compared with teriparatide, an established anabolic agent. Design: This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. Setting: This study took both in both US and Canadian sites. Participants: Sixty-nine postmenopausal women with osteoporosis were included. Interventions: Teriparatide (20 μg/day) for 6 months and denosumab (60 mg once) were used in this study. Main Outcome Measure: Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface, histomorphometric indices in four bone envelopes, and BTM and iPTH at baseline, 1, 3, and 6 months was undertaken. Results: After denosumab, iPTH peaked at month 1 (P < .001), then declined, remaining above baseline through month 6 (P ≤ .01); after teriparatide, iPTH declined at all time points (P < .001). From baseline to month 3, cancellous mineralizing surface/bone surface increased with teriparatide and decreased with denosumab and at month 3, was higher with teriparatide. Similar results were observed in other bone envelopes. BTMs increased from baseline in teriparatide-treated subjects (procollagen type 1 N-terminal propeptide at month 1 and carboxyterminal cross-linking telopeptide of type 1 collagen at month 3); procollagen type 1 N-terminal propeptide and carboxyterminal cross-linking telopeptide of type 1 collagen decreased from baseline at all time points in denosumab-treated subjects. Conclusions: Denosumab treatment increased iPTH but inhibited bone formation indices. In contrast, teriparatide treatment decreased iPTH but stimulated bone formation indices. These findings are not consistent with the hypothesis of early indirect anabolic effect with denosumab. PMID:26859106

Effects of the two types of anorexia nervosa (binge eating/purging and restrictive) on bone metabolism in female patients.

PubMed

Maïmoun, Laurent; Guillaume, Sébastien; Lefebvre, Patrick; Bertet, Helena; Seneque, Maude; Philibert, Pascal; Picot, Marie-Christine; Dupuy, Anne-Marie; Paris, Françoise; Gaspari, Laura; Ben Bouallègue, Fayçal; Courtet, Philippe; Mariano-Goulart, Denis; Renard, Eric; Sultan, Charles

2018-06-01

This study compared the profiles of the two types of anorexia nervosa (AN; restrictive: AN-R, and binge eating/purging: AN-BP) in terms of body composition, gynaecological status, disease history and the potential effects on bone metabolism. Two hundred and eighty-six women with AN (21.8 ± 6.5 years; 204 AN-R and 82 AN-BP) and 130 age-matched controls (CON; 22.6 ± 6.8 years) were enrolled. Areal bone mineral density (aBMD) was determined using DXA and resting energy expenditure (REE) was indirectly assessed using calorimetry. Markers of bone formation (osteocalcin [OC], procollagen type I N-terminal propeptide [PINP] and resorption (type I-C telopeptide breakdown products [CTX]) and leptin were concomitantly evaluated. Anorexia nervosa patients presented an alteration in aBMD and bone turnover. When compared according to type, AN-BP were older than AN-R and showed less severe undernutrition, lower CTx levels, longer duration of AN, and higher REE levels and aBMD at radius and lumbar spine. After adjustment for age, weight and hormonal contraceptive use, the aBMD and CTx differences disappeared. In both AN groups, aBMD was positively correlated with anthropometric parameters and negatively correlated with durations of AN and amenorrhoea, the bone formation markers (OC and PINP) and the leptin/fat mass ratio. REE was positively correlated with aBMD in AN-R patients only. This study shows the profiles of AN patients according to AN type. However, the impact of the profile characteristics on bone status, although significant, was minor and disappeared after multiple adjustments. The positive correlation between REE and aBMD reinforces the concept that energy disposal and bone metabolism are strongly interdependent. © 2018 John Wiley & Sons Ltd.

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

PubMed

Kitajima, Kazuhiro; Fukushima, Kazuhito; Yamamoto, Shingo; Kato, Takashi; Odawara, Soichi; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Nakanishi, Yukako; Kanematsu, Akihiro; Nojima, Michio; Hirota, Shozo

2017-08-01

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

Using titanium LPW-TI64-GD23-TYPE5 in the individual contour grafting of bone defects with 3D implants

NASA Astrophysics Data System (ADS)

Bazlov, V. A.; Mamuladze, T. Z.; Pavlov, V. V.; Prohorenko, V. M.; Sadovoy, M. A.; Fomichev, N. G.; Efimenko, M. V.; Mamonova, E. V.; Aronov, A. M.

2017-09-01

The paper proposed a method of replacement of bone defects of a basin with individual 3D-printed implants of medical titanium LPW-TI64-GD23-TYPE5 ASTM F136. The design of the implant was carried out in view of determining the density of the surrounding bone tissue by Hounsfield's scale. We used the method of volume printing by type multiselecting laser sintering. A clinical example of using the method of individual contouring of the defect of bones of a basin with the assessment of bone density by Hounsfield's scale was given. The method of individual contouring of the defect of the basin bones with the assessment of bone density by Hounsfield's scale enables the surgeon to more accurately determine the tactics of surgical intervention: opting for bone grafting or the use of augmented. In the case of manufacturing an individual 3D augment, this method gives the possibility to adjust its geometry taking into account the density of the bone tissue, thereby giving it additional stability. If there is a need for screws—we can preadjust the length and direction of stroke so that the main part of the screw might pass in the support ability area of the bone tissue. We believe that the software and the approach to preoperative planning we have used can make surgery more convenient for the surgeon and personnel of the medical institution.

Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature.

PubMed

Morad, Golnaz; Kheiri, Lida; Khojasteh, Arash

2013-12-01

This review of literature was aimed to assess in vivo experiments which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone regeneration. An electronic search of English-language papers was conducted on PubMed database. Studies that assessed the use of DPSCs in bone regeneration in vivo were included and experiments evaluating regeneration of hard tissues other than bone were excluded. The retrieved articles were thoroughly reviewed according to the source of stem cell, cell carrier, the in vivo experimental model, defect type, method of evaluating bone regeneration, and the obtained results. Further assessment of the results was conducted by classifying the studies based on the defect type. Seventeen papers formed the basis of this systematic review. Sixteen out of 17 experiments were performed on animal models with mouse and rat being the most frequently used animal models. Seven out of 17 animal studies, contained subcutaneous pockets on back of the animal for stem cell implantation. In only one study hard tissue formation was not observed. Other types of defects used in the retrieved studies, included cranial defects and mandibular bone defects, in all of which bone formation was reported. When applied in actual bone defects, DPSCs were capable of regenerating bone. Nevertheless, a precise conclusion regarding the efficiency of DPSCs for bone regeneration is yet to be made, considering the limited number of the in vivo experiments and the heterogeneity within their methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

The skeletal structure of insulin-like growth factor I-deficient mice

NASA Technical Reports Server (NTRS)

Bikle, D.; Majumdar, S.; Laib, A.; Powell-Braxton, L.; Rosen, C.; Beamer, W.; Nauman, E.; Leary, C.; Halloran, B.

2001-01-01

The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.