Does Excision of Heterotopic Ossification of the Elbow Result in Satisfactory Patient-Rated Outcomes?

PubMed

Sandeep, K N; Suresh, G; Gopisankar, B; Abhishek, N; Sujiv, A

2017-03-01

Treatment of heterotopic ossification (HO) of the elbow is challenging and fraught with complications. Patients who sustain direct trauma to the elbow joint, the central nervous system, and thermal burns are at increased risk for development of HO. There is a paucity of studies and reports on patient's self-evaluation after the excision of the heterotopic ossification. This retrospective study assessed outcomes after excision of heterotopic ossification around the elbow in a cohort of ten patients operated from 2012 to 2015. The outcome assessment was done by the Mayo Elbow Performance index (MEPI) and the American Shoulder and Elbow Surgeons-Elbow score (ASES-E scores). The mean follow-up was 18.11 months after the operation. The Mayo Elbow Performance Score was excellent in two elbows, good in six and fair in two. The mean gain in flexion-extension arc after excision of HO was 80 degrees. All of the patients had residual flexion deformity postoperatively. Eight of the nine patients were able to do activities requiring flexion at final follow-up. Excision of HO around the elbow is associated with satisfactory patient-rated outcomes in spite of failure to regain full range of motion.

Circulating osteogentic precursor cells in non-hereditary heterotopic ossification.

PubMed

Egan, Kevin P; Duque, Gustavo; Keenan, Mary Ann; Pignolo, Robert J

2018-04-01

Non-hereditary heterotopic ossification (NHHO) may occur after musculoskeletal trauma, central nervous system (CNS) injury, or surgery. We previously described circulating osteogenic precursor (COP) cells as a bone marrow-derived type 1 collagen + CD45 + subpopulation of mononuclear adherent cells that are able of producing extraskeletal ossification in a murine in vivo implantation assay. In the current study, we performed a tissue analysis of COP cells in NHHO secondary to defined conditions, including traumatic brain injury, spinal cord injury, cerebrovascular accident, trauma without neurologic injury, and joint arthroplasty. All bone specimens revealed the presence of COP cells at 2-14 cells per high power field. COP cells were localized to early fibroproliferative and neovascular lesions of NHHO with evidence for their circulatory status supported by their presence near blood vessels in examined lesions. This study provides the first systematic evaluation of COP cells as a contributory histopathological finding associated with multiple forms of NHHO. These data support that circulating, hematopoietic-derived cells with osteogenic potential can seed inflammatory sites, such as those subject to soft tissue injury, and due to their migratory nature, may likely be involved in seeding sites distant to CNS injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk of symptomatic heterotopic ossification following plate osteosynthesis in multiple trauma patients: an analysis in a level-1 trauma centre

PubMed Central

Zeckey, Christian; Hildebrand, Frank; Mommsen, Philipp; Schumann, Julia; Frink, Michael; Pape, Hans-Christoph; Krettek, Christian; Probst, Christian

2009-01-01

Background Symptomatic heterotopic ossification (HO) in multiple trauma patients may lead to follow up surgery, furthermore the long-term outcome can be restricted. Knowledge of the effect of surgical treatment on formation of symptomatic heterotopic ossification in polytrauma is sparse. Therefore, we test the effects of surgical treatment (plate osteosynthesis or intramedullary nailing) on the formation of heterotopic ossification in the multiple trauma patient. Methods We retrospectively analysed prospectively documented data of blunt multiple trauma patients with long bone fractures which were treated at our level-1 trauma centre between 1997 and 2005. Patients were distributed to 2 groups: Patients treated by intramedullary nails (group IMN) or plate osteosynthesis (group PLATE) were compared. The expression and extension of symptomatic heterotopic ossifications on 3-6 months follow-up x-rays in antero-posterior (ap) and lateral views were classified radiologically and the maximum expansion was measured in millimeter (mm). Additionally, ventilation time, prophylactic medication like indomethacine and incidence and correlation of head injuries were analysed. Results 101 patients were included in our study, 79 men and 22 women. The fractures were treated by intramedullary nails (group IMN n = 50) or plate osteosynthesis (group PLATE n = 51). Significantly higher radiologic ossification classes were detected in group PLATE (2.9 ± 1.3) as compared to IMN (2.2 ± 1.1; p = 0.013). HO size in mm ap and lateral showed a tendency towards larger HOs in the PLATE group. Additionally PLATE group showed a higher rate of articular fractures (63% vs. 28% in IMN) while IMN demonstrated a higher rate of diaphyseal fractures (72% vs. 37% in PLATE; p = 0.003). Ventilation time, indomethacine and incidence of head injuries showed no significant difference between groups. Conclusion Fracture care with plate osteosynthesis in polytrauma patients is associated with larger formations

Vessel formation is induced prior to the appearance of cartilage in BMP-2-mediated heterotopic ossification

USDA-ARS?s Scientific Manuscript database

Heterotopic ossification (HO), or endochondral bone formation at nonskeletal sites, often results from traumatic injury and can lead to devastating consequences. Alternatively, the ability to harness this phenomenon would greatly enhance current orthopedic tools for treating segmental bone defects. ...

Treatment of heterotopic ossification through remote ATP hydrolysis.

PubMed

Peterson, Jonathan R; De La Rosa, Sara; Eboda, Oluwatobi; Cilwa, Katherine E; Agarwal, Shailesh; Buchman, Steven R; Cederna, Paul S; Xi, Chuanwu; Morris, Michael D; Herndon, David N; Xiao, Wenzhong; Tompkins, Ronald G; Krebsbach, Paul H; Wang, Stewart C; Levi, Benjamin

2014-09-24

Heterotopic ossification (HO) is the pathologic development of ectopic bone in soft tissues because of a local or systemic inflammatory insult, such as burn injury or trauma. In HO, mesenchymal stem cells (MSCs) are inappropriately activated to undergo osteogenic differentiation. Through the correlation of in vitro assays and in vivo studies (dorsal scald burn with Achilles tenotomy), we have shown that burn injury enhances the osteogenic potential of MSCs and causes ectopic endochondral heterotopic bone formation and functional contractures through bone morphogenetic protein-mediated canonical SMAD signaling. We further demonstrated a prevention strategy for HO through adenosine triphosphate (ATP) hydrolysis at the burn site using apyrase. Burn site apyrase treatment decreased ATP, increased adenosine 3',5'-monophosphate, and decreased phosphorylation of SMAD1/5/8 in MSCs in vitro. This ATP hydrolysis also decreased HO formation and mitigated functional impairment in vivo. Similarly, selective inhibition of SMAD1/5/8 phosphorylation with LDN-193189 decreased HO formation and increased range of motion at the injury site in our burn model in vivo. Our results suggest that burn injury-exacerbated HO formation can be treated through therapeutics that target burn site ATP hydrolysis and modulation of SMAD1/5/8 phosphorylation. Copyright © 2014, American Association for the Advancement of Science.

High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model.

PubMed

Ranganathan, Kavitha; Hong, Xiaowei; Cholok, David; Habbouche, Joe; Priest, Caitlin; Breuler, Christopher; Chung, Michael; Li, John; Kaura, Arminder; Hsieh, Hsiao Hsin Sung; Butts, Jonathan; Ucer, Serra; Schwartz, Ean; Buchman, Steven R; Stegemann, Jan P; Deng, Cheri X; Levi, Benjamin

2018-04-01

Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy. Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n=3-5 limbs per time point). To compare the use of SUSI in different types of injury models, mice (n=5 per group) underwent either burn/tenotomy or skin incision injury and were imaged using a 55MHz probe on VisualSonics VEVO 770 system at one week post injury to evaluate the ability of SUSI to distinguish between edema and HO. Average acoustic concentration (AAC) and average scatterer diameter (ASD) were calculated for each ultrasound image frame. Micro CT was used to calculate the total volume of HO. Histology was used to confirm bone formation. Using SUSI, HO was visualized as early as 1week after injury. HO was visualized earliest by 4weeks after injury by micro CT. The average acoustic concentration of HO was 33% more than that of the control limb (n=5). Spectroscopic foci of HO present at 1week that persisted throughout all time points correlated with the HO present at 9weeks on micro CT imaging. SUSI visualizes HO as early as one week after injury in an animal model. SUSI represents a new imaging modality with promise for early diagnosis of HO. Copyright © 2018 Elsevier Inc. All rights reserved.

Bioburden Increases Heterotopic Ossification Formation in an Established Rat Model.

PubMed

Pavey, Gabriel J; Qureshi, Ammar T; Hope, Donald N; Pavlicek, Rebecca L; Potter, Benjamin K; Forsberg, Jonathan A; Davis, Thomas A

2015-09-01

Heterotopic ossification (HO) develops in a majority of combat-related amputations wherein early bacterial colonization has been considered a potential early risk factor. Our group has recently developed a small animal model of trauma-induced HO that incorporates many of the multifaceted injury patterns of combat trauma in the absence of bacterial contamination and subsequent wound colonization. We sought to determine if (1) the presence of bioburden (Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus [MRSA]) increases the magnitude of ectopic bone formation in traumatized muscle after amputation; and (2) what persistent effects bacterial contamination has on late microbial flora within the amputation site. Using a blast-related HO model, we exposed 48 rats to blast overpressure, femur fracture, crush injury, and subsequent immediate transfemoral amputation through the zone of injury. Control injured rats (n = 8) were inoculated beneath the myodesis with phosphate-buffered saline not containing bacteria (vehicle) and treatment rats were inoculated with 1 × 10(6) colony-forming units of A baumannii (n = 20) or MRSA (n = 20). All animals formed HO. Heterotopic ossification was determined by quantitative volumetric measurements of ectopic bone at 12-weeks postinjury using micro-CT and qualitative histomorphometry for assessment of new bone formation in the residual limb. Bone marrow and muscle tissue biopsies were collected from the residual limb at 12 weeks to quantitatively measure the bioburden load and to qualitatively determine the species-level identification of the bacterial flora. At 12 weeks, we observed a greater volume of HO in rats infected with MRSA (68.9 ± 8.6 mm(3); 95% confidence interval [CI], 50.52-85.55) when compared with A baumannii (20.9 ± 3.7 mm(3); 95% CI, 13.61-28.14; p < 0.001) or vehicle (16.3 ± 3.2 mm(3); 95% CI, 10.06-22.47; p < 0.001). Soft tissue and marrow from the residual limb of rats inoculated with A

Heterotopic ossification in civilians with lower limb amputations.

PubMed

Matsumoto, Mary E; Khan, Mohammed; Jayabalan, Prakash; Ziebarth, Jessica; Munin, Michael C

2014-09-01

To report the incidence of symptomatic heterotopic ossification (HO) in a defined civilian amputee population, describe its characteristics, and compare these findings to published data in military amputees. Retrospective chart analysis from July 1998 to July 2009. Ambulatory amputee clinic within a large university medical center. Adults with lower limb amputation (N=158). Not applicable. Patients with symptomatic HO confirmed by radiographs. A total of 261 patients were evaluated; 158 met inclusion criteria, with 59% having traumatic etiology, 18% vascular etiology, 22% infection, and 1% tumor. Symptomatic HO was diagnosed in 36 (22.8%) patients, and 94% patients had mild HO on radiographic scoring. Rate of HO in amputations related to trauma was not increased compared with those of other etiologies. Surgical resection of the ectopic bone was required in 4 (11%) patients. HO is seen commonly after civilian lower limb amputation regardless of etiology. The prevalence was less than that observed in previous reports from military populations. This is the first report estimating the prevalence of HO in adult civilian amputees. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Early Diagnosis of Fibrodysplasia Ossificans Progressiva

PubMed Central

Kaplan, Frederick S.; Xu, Meiqi; Glaser, David L.; Collins, Felicity; Connor, Michael; Kitterman, Joseph; Sillence, David; Zackai, Elaine; Ravitsky, Vardit; Zasloff, Michael; Ganguly, Arupa; Shore, Eileen M.

2012-01-01

BACKGROUND Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes and by progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodys-plasia ossificans progressiva are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures that can cause lifelong disability. Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification. METHODS We recently evaluated 7 children for diagnosis of fibrodysplasia ossificans progressiva before the onset of heterotopic ossification. A medical history, physical examination, and skeletal survey were obtained on all of the patients, as well as clinical genetic testing for the canonical fibrodysplasia ossificans progressiva mutation. RESULTS All 7 of the children (4 girls and 3 boys; ages 3 months to 6 years) had congenital malformations of the great toes, but none had radiographic evidence of heterotopic ossification at the time of evaluation. Five of the 7 children had soft tissue lesions of the neck and back, suggestive of early fibrodysplasia ossificans progressiva flare-ups, 3 of whom had undergone invasive diagnostic procedures that exacerbated their condition. Two children had no history or signs of soft tissue swelling or flare-ups. DNA sequence analysis found that all 7 of the children had the recurrent fibrodysplasia ossificans progressiva missense mutation, a single nucleotide substitution (c.617G>A) at codon 206 in the glycine-serine activation domain of activin receptor IA, a bone morphogenetic protein type 1 receptor. CONCLUSION Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory

Heterotopic ossification resection after open periarticular combat-related elbow fractures.

PubMed

Wilson, Kevin W; Dickens, Jonathan F; Heckert, Reed; Tintle, Scott M; Keeling, John J; Andersen, Romney C; Potter, Benjamin K

2013-01-01

A retrospective review was performed to evaluate the outcomes and complications following heterotopic ossification (HO) resection and lysis of adhesion procedures for posttraumatic contracture, after combat-related open elbow fractures. From 2004 to 2011, HO resection was performed on 30 blast-injured elbows at a mean 10 months after injury. Injuries included 8 (27%) Gustilo-Anderson type II fractures, 8 (27%) type III-A, 10 (33%) III-B, and 4 (13%) III-C. Mean preoperative flexion-extension range of motion (ROM) was 36.4°, compared with mean postoperative ROM of 83.6°. Mean gain of motion was 47.2°. Traumatic brain injury, need for flap, and nerve injury did not appear to have a significant effect on preoperative or postoperative ROM. Complications included one fracture, six recurrent contractures, and one nerve injury. The results and complications of HO resection for elbow contracture following high-energy, open injuries from blast trauma are generally comparable to those reported for HO resection following lower energy, closed injuries.

Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification

PubMed Central

Regard, Jean B.; Malhotra, Deepti; Gvozdenovic-Jeremic, Jelena; Josey, Michelle; Chen, Min; Weinstein, Lee S.; Lu, Jianming; Shore, Eileen M.; Kaplan, Frederick S.; Yang, Yingzi

2014-01-01

Bone formation is exquisitely controlled in space and time. Heterotopic ossification (HO), the pathologic formation of extra-skeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and lethal. However, the underlying molecular mechanisms are largely unknown. Here we demonstrate that Gαs restricts bone formation to the skeleton by inhibiting Hedgehog (Hh) signaling in mesenchymal progenitor cells. In progressive osseous heteroplasia (POH), a human disease caused by null mutations in GNAS that encodes Gαs, HH signaling is upregulated in ectopic osteoblasts and progenitor cells. Ectopic Hh signaling is sufficient to induce HO, while Hh signaling inhibition blocks HO in animal models. As our previous work has shown that GNAS gain of function mutations upregulate WNT/β-Catenin signaling in fibrous dysplasia (FD), our findings identify Gαs as a critical regulator of osteoblast differentiation by maintaining a balance between two key signaling pathways: Wnt/β-catenin and Hh. HH signaling inhibitors developed for cancer therapy may be repurposed to treat HO and other diseases caused by GNAS inactivation. PMID:24076664

Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients

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

MacLennan, I.; Keys, H.M.; Evarts, C.M.

1984-01-01

Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible onmore » postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized.« less

Heterotopic Ossification in Wartime Wounds

DTIC Science & Technology

2010-01-01

musculoskeletal system. J. Bone Joint Surg. 84-A: 1221- 1234, 2002 . 32. Champion, H . R., Bellamy, R. F., Robens, C. P., et al. A profile of combat injury...rat model. Am. J. Orthop. 37:EI33-137, 2008. 79. Mullis, B . H ., et al. Effect of COX-2 inhibitors and non- steroidal anti-inflammatory drugs on a...T. J., et al. The effect of biphosphonate on induced heterotopic bone. Clin. Orthop. Relat. Res. 272:259-267, 1991. 92. Thomas, B . J., Amstutz, H

Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling.

PubMed

Jiang, Huaji; Chen, Yuhui; Chen, Guorong; Tian, Xinggui; Tang, Jiajun; Luo, Lei; Huang, Minjun; Yan, Bin; Ao, Xiang; Zhou, Wen; Wang, Liping; Bai, Xiaochun; Zhang, Zhongmin; Wang, Liang; Xian, Cory J

2018-02-01

Leptin, an adipocyte-derived cytokine associated with bone metabolism, is believed to play a critical role in the pathogenesis of heterotopic ossification (HO). The effect and underlying action mechanism of leptin were investigated on osteogenic differentiation of tendon-derived stem cells (TDSCs) in vitro and the HO formation in rat tendons. Isolated rat TDSCs were treated with various concentrations of leptin in the presence or absence of mTORC1 signaling specific inhibitor rapamycin in vitro. A rat model with Achilles tenotomy was employed to evaluate the effect of leptin on HO formation together with or without rapamycin treatment. In vitro studies with TDSCs showed that leptin increased the expression of osteogenic biomarkers (alkaline phosphatase, runt-related transcription factor 2, osterix, osteocalcin) and enhanced mineralization of TDSCs via activating the mTORC1 signal pathway (as indicated by phosphorylation of p70 ribosomal S6 kinase 1 and p70 ribosomal S6). However, mTORC1 signaling blockade with rapamycin treatment suppressed leptin-induced osteogenic differentiation and mineralization. In vivo studies showed that leptin promoted HO formation in the Achilles tendon after tenotomy, and rapamycin treatment blocked leptin-induced HO formation. In conclusion, leptin can promote TDSC osteogenic differentiation and heterotopic bone formation via mTORC1 signaling in both vitro and vivo model, which provides a new potential therapeutic target for HO prevention. © 2017 Wiley Periodicals, Inc.

Sensory Nerve Induced Inflammation Contributes to Heterotopic Ossification

PubMed Central

Salisbury, Elizabeth; Rodenberg, Eric; Sonnet, Corinne; Hipp, John; Gannon, Francis H.; Vadakkan, Tegy J.; Dickinson, Mary E.; Olmsted-Davis, Elizabeth A.; Davis, Alan R.

2012-01-01

Heterotopic ossification (HO), or bone formation in soft tissues, is often the result of traumatic injury. Much evidence has linked the release of BMPs (bone morphogenetic proteins) upon injury to this process. HO was once thought to be a rare occurrence, but recent statistics from the military suggest that as many as 60% of traumatic injuries, resulting from bomb blasts, have associated HO. In this study, we attempt to define the role of peripheral nerves in this process. Since BMP2 has been shown previously to induce release of the neuroinflammatory molecules, substance P (SP) and calcitonin gene related peptide (CGRP), from peripheral, sensory neurons, we examined this process in vivo. SP and CGRP are rapidly expressed upon delivery of BMP2 and remain elevated throughout bone formation. In animals lacking functional sensory neurons (TRPV1−/−), BMP2-mediated increases in SP and CGRP were suppressed as compared to the normal animals, and HO was dramatically inhibited in these deficient mice, suggesting that neuroinflammation plays a functional role. Mast cells, known to be recruited by SP and CGRP, were elevated after BMP2 induction. These mast cells were localized to the nerve structures and underwent degranulation. When degranulation was inhibited using cromolyn, HO was again reduced significantly. Immunohistochemical analysis revealed nerves expressing the stem cell markers nanog and Klf4, as well as the osteoblast marker osterix, after BMP2 induction, in mice treated with cromolyn. The data collectively suggest that BMP2 can act directly on sensory neurons to induce neurogenic inflammation, resulting in nerve remodeling and the migration/release of osteogenic and other stem cells from the nerve. Further, blocking this process significantly reduces HO, suggesting that the stem cell population contributes to bone formation. PMID:21678472

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

PubMed Central

Torossian, Frédéric; Guerton, Bernadette; Anginot, Adrienne; Alexander, Kylie A.; Desterke, Christophe; Soave, Sabrina; Tseng, Hsu-Wen; Arouche, Nassim; Boutin, Laetitia; Kulina, Irina; Salga, Marjorie; Jose, Beulah; Pettit, Allison R.; Clay, Denis; Vlachos, Erica; Genet, Guillaume; Debaud, Charlotte; Denormandie, Philippe; Genet, François; Sims, Natalie A.; Banzet, Sébastien; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2017-01-01

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury–induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. PMID:29093266

The predisposing factors for the heterotopic ossification after cervical artificial disc replacement.

PubMed

Yi, Seong; Shin, Dong Ah; Kim, Keung Nyun; Choi, Gwihyun; Shin, Hyun Chul; Kim, Keun Su; Yoon, Do Heum

2013-09-01

Heterotopic ossification (HO) is defined as a formation of bone outside the skeletal system. The reported HO occurrence rate in cervical artificial disc replacement (ADR) is unexpectedly high and is known to vary. However, the predisposing factors for HO in cervical ADR have not yet been elucidated. Investigation of the predisposing factors of HO in cervical arthroplasty and the relationship between degeneration of the cervical spine and HO occurrence. Retrospective study to discover predisposing factors of HO in cervical arthroplasty. A total of 170 patients who underwent cervical ADR were enrolled including full follow-up clinical and radiologic data. Radiologic outcomes were assessed by identification of HOs according to McAfee's classifications. This study enrolled a total of 170 patients who underwent cervical ADR. Pre-existing degenerative change included anterior or posterior osteophytes, ossification of the anterior longitudinal ligament, posterior longitudinal ligament, or ligamentum nuchae. The relationships between basic patient data, pre-existing degenerative change, and HO were investigated using linear logistic regression analysis. Among all 170 patients, HO was found in 69 patients (40.6%). Among the postulated predisposing factors, only male gender and artificial disc device type were shown to be statistically significant. Unexpectedly, preoperative degenerative changes in the cervical spine exerted no significant influence on the occurrence of HOs. The odds ratio of male gender compared with female gender was 2.117. With regard to device type, the odds ratios of Mobi-C (LDR medical, Troyes, France) and ProDisc-C (Synthes, Inc., West Chester, PA, USA) were 5.262 and 7.449, respectively, compared with the Bryan disc. Definite differences in occurrence rate according to the gender of patients and the prosthesis type were identified in this study. Moreover, factors indefinably expected to influence HO in the past were not shown to be risk factors

Prevention and Treatment of Heterotopic Ossification

DTIC Science & Technology

2012-02-01

suggest that low oxygen tension critically influences chondrocyte differentiation by accelerating the growth of mesenchymal stem cells and promoting...ossification, we focused on the microenvironmental conditions needed to induce mesenchymal stem cells to differentiate to chondrocytes, which form the...this is due in part to the use of different family members in for extravasating lymphocytes versus mesenchymal stem cells . Since entry of

The Impact of Body Mass Index on Heterotopic Ossification

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

Mourad, Waleed Fouad, E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

2012-04-01

Purpose: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). Methods and Materials: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT {+-} indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT {+-} indomethacinmore » in preventing HO in patients with different BMI. Results: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0 Multiplication-Sign (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). Conclusions: Despite similar surgical treatment and prophylactic measures (RT {+-} indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.« less

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2013-10-01

therapies for prevention or mitigation of HO can be optimally targeted. This study seeks to contribute to advancement in each of these key areas...NOTES 14. ABSTRACT This study will recruit wounded warriors with severe extremity trauma, which places them at high risk for heterotopic... therapies for prevention or mitigation of HO. 15. SUBJECT TERMS Wound healing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18

SU-G-JeP3-07: Real-Time Image Guided Radiation Therapy for Heterotopic Ossification in Patients After Hip Replacement

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

Le, A; Jiang, S; Timmerman, R

Purpose: To demonstrate the feasibility of using CBCT in a real-time image guided radiation therapy (IGRT) for single fraction heterotopic ossification (HO) in patients after hip replacement. In this real-time procedure, all steps, from simulation, imaging, planning to treatment delivery, are performed at the treatment unit in one appointment time slot. This work promotes real-time treatment to create a paradigm shift in the single fraction radiation therapy. Methods: An integrated real-time IGRT for HO was developed and tested for radiation treatment of heterotopic ossification for patient after hip replacement. After CBCT images are acquired at the linac, and sent tomore » the treatment planning system, the physician determines the field and/or draws a block. Subsequently, a simple 2D AP/PA plan with prescription of 700 cGy is created on-the-fly for physician to review. Once the physician approves the plan, the patient is treated on the same simulation position. This real-time treatment requires the team of attending physician, physicist, therapists, and dosimetrist to work in harmony to achieve all the steps in a timely manner. Results: Ten patients have been treated with this real-time treatment, having the same beams arrangement treatment plan and prescription as our clinically regular CT-based 2D plans. The average time for these procedures are 52.9 ±10.7 minutes from the time patient entered the treatment room until s/he exited, and 37.7 ±8.6 minutes from starting CBCT until last beam delivered. Conclusion: The real-time IGRT for HO treatment has been tested and implemented to be a clinically accepted procedure. This one-time appointment greatly enhances the waiting time, especially when patients in high level of pain, and provides a convenient approach for the whole clinical staff. Other disease sites will be also tested with this new technology.« less

Incidence of Heterotopic Ossification after Surface and Conventional Total Hip Arthroplasty: A Comparative Study Using Anterolateral Approach and Indomethacin Prophylaxis

PubMed Central

Sandri, Andrea; Sambugaro, Elena

2013-01-01

The incidence and severity of heterotopic ossification (HO) in two homogeneous groups of patients that received surface replacement arthroplasty (SRA) and conventional total hip arthroplasty (THA) were evaluated retrospectively. Thirty-nine patients undergoing 42 hip resurfacing procedures and 41 primary cementless THAs through an anterolateral approach received a 10-day course of 150 mg/die of indomethacin postoperatively. The median surgical time was 190 minutes and 156 minutes, respectively (P < 0.003). At a minimum 1-year followup, the development of HO was assessed on standard X-ray using Brooker grading. Ectopic bone formation was detected in five cases (11.9%, two Brooker grade I and three grade II) in the SRA group and in 14 hips (34.1%, 12 grade I and two grade II) treated with conventional THA, but the difference was not significant (P < 0.11). No clinically relevant periprosthetic ossification (Brooker III or IV) occurred in both groups. Although the difference was not statistically significant, the incidence of HO after SRA was lower than conventional THA. More extensive soft tissue trauma, bone debris, and longer operative time in hip resurfacing are not likely to be absolute risk factors for HO. Further investigations including larger patient populations are needed to confirm these findings. PMID:23865045

Influence of Bone and Muscle Injuries on the Osteogenic Potential of Muscle Progenitors: Contribution of Tissue Environment to Heterotopic Ossification

PubMed Central

Molligan, Jeremy; Mitchell, Reed; Schon, Lew; Achilefu, Samuel; Zahoor, Talal; Cho, Young; Loube, Jeffery

2016-01-01

By using surgical mouse models, this study investigated how the tissue environment influences the osteogenic potential of muscle progenitors (m-progenitors) and potentially contributes to heterotopic ossification (HO). Injury was induced by clamping the gluteus maximus and medius (group M) or osteotomy of greater trochanter (group O) on the right hip, as well as combined muscle injury and osteotomy of greater trochanter (group M+O). The gluteus maximus and medius of the operated hips were harvested at days 1, 3, 5, and 10 for isolation of m-progenitors. The cells were cultured in an osteogenic medium for 3 weeks, and osteogenesis was evaluated by matrix mineralization and the expression of osteogenesis-related genes. The expression of type I collagen, RUNX2 (runt-related transcription factor 2), and osteocalcin by the m-progenitors of group M+O was significantly increased, compared with groups M and O. Osteogenic m-progenitors in group O increased the expression of bone morphogenetic protein 2 and also bone morphogenetic protein antagonist differential screening-selected gene aberrative in neuroblastoma. On histology, there was calcium deposition mostly in the muscles of group M+O harvested at day 10. CD56, representing myogenic progenitors, was highly expressed in the m-progenitors isolated from group M (day 10), but m-progenitors of group M+O (day 10) exhibited the highest expression of platelet-derived growth factor receptor α (PDGFR-α), a marker of muscle-derived mesenchymal stem cells (M-MSCs). The expressions of PDGFR-α and RUNX2 were colocalized in osteogenic m-progenitors. The data indicate that the tissue environment simulated in the M+O model is a favorable condition for HO formation. Most likely, M-MSCs, rather than myogenic progenitors, in the m-progenitors participate in HO formation. Significance The prevalence of traumatic heterotopic ossification (HO) is high in war injury. The pathogenesis of HO is still unknown. This study clarified the

Influence of Bone and Muscle Injuries on the Osteogenic Potential of Muscle Progenitors: Contribution of Tissue Environment to Heterotopic Ossification.

PubMed

Molligan, Jeremy; Mitchell, Reed; Schon, Lew; Achilefu, Samuel; Zahoor, Talal; Cho, Young; Loube, Jeffery; Zhang, Zijun

2016-06-01

: By using surgical mouse models, this study investigated how the tissue environment influences the osteogenic potential of muscle progenitors (m-progenitors) and potentially contributes to heterotopic ossification (HO). Injury was induced by clamping the gluteus maximus and medius (group M) or osteotomy of greater trochanter (group O) on the right hip, as well as combined muscle injury and osteotomy of greater trochanter (group M+O). The gluteus maximus and medius of the operated hips were harvested at days 1, 3, 5, and 10 for isolation of m-progenitors. The cells were cultured in an osteogenic medium for 3 weeks, and osteogenesis was evaluated by matrix mineralization and the expression of osteogenesis-related genes. The expression of type I collagen, RUNX2 (runt-related transcription factor 2), and osteocalcin by the m-progenitors of group M+O was significantly increased, compared with groups M and O. Osteogenic m-progenitors in group O increased the expression of bone morphogenetic protein 2 and also bone morphogenetic protein antagonist differential screening-selected gene aberrative in neuroblastoma. On histology, there was calcium deposition mostly in the muscles of group M+O harvested at day 10. CD56, representing myogenic progenitors, was highly expressed in the m-progenitors isolated from group M (day 10), but m-progenitors of group M+O (day 10) exhibited the highest expression of platelet-derived growth factor receptor α (PDGFR-α), a marker of muscle-derived mesenchymal stem cells (M-MSCs). The expressions of PDGFR-α and RUNX2 were colocalized in osteogenic m-progenitors. The data indicate that the tissue environment simulated in the M+O model is a favorable condition for HO formation. Most likely, M-MSCs, rather than myogenic progenitors, in the m-progenitors participate in HO formation. The prevalence of traumatic heterotopic ossification (HO) is high in war injury. The pathogenesis of HO is still unknown. This study clarified the contribution of a

Genetic disorders with heterotopic ossificans

PubMed Central

Sankar, Ruthiramurthy; Gowrishankar, Kalpana; Viswanathan, Saraswati

2015-01-01

Fibrodysplasia ossificans progressiva (FOP) and progressive ossific heteroplasia (POH) are rare genetic disorders characterized by heterotopic bone formation leading to progressive loss of mobility and function. We report three cases of these rare disorders (two cases of FOP and one case of POH), which were clinically diagnosed and underwent genetic analysis. The aim of this report is to highlight the clinical features and the differences between these two conditions. We would also like to emphasize on the morbidity that can arise from unnecessary invasive investigations for diagnostic purposes. PMID:26015640

Analysis of bone-cartilage-stromal progenitor populations in trauma induced and genetic models of heterotopic ossification

PubMed Central

Agarwal, Shailesh; Loder, Shawn; Li, Shuli; Shrestha, Swati; Li, Jon; Zhao, Bin; Mishina, Yuji; James, Aaron; Levi, Benjamin

2016-01-01

Heterotopic ossification (HO), the formation of extra-skeletal bone in soft tissues, is a pathologic process occurring after substantial burns or trauma, or in patients with type I bone morphogenetic protein (BMP) receptor hyperactivating mutations. Identifying the cells responsible for de novo bone formation during adulthood is of critical importance for therapeutic and regenerative purposes. Using a model of trauma-induced HO with hindlimb Achilles’ tenotomy and dorsal burn injury and a genetic non-trauma HO model (Nfatc1-Cre/caAcvr1fl/wt), we demonstrate enrichment of previously defined bone-cartilage-stromal progenitor cells (BCSP: AlphaV+/CD105+/Tie2-/CD45-/Thy1-/6C3-) at the site of HO formation when compared with marrow isolated from the ipsilateral hindlimb, or from tissue of the contralateral, uninjured hindlimb. Upon transplantation into tenotomy sites soon after injury, BCSPs isolated from neonatal mice or developing HO incorporate into the developing lesion in cartilage and bone and express chondrogenic and osteogenic transcription factors. Additionally, BCSPs isolated from developing HO similarly incorporate into new HO lesions upon transplantation. Finally, adventitial cells, but not pericytes, appear to play a supportive role in HO formation. Our findings indicate that BCSPs contribute to de novo bone formation during adulthood and may hold substantial regenerative potential. PMID:27068890

A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

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

Mourad, Waleed F., E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Packianathan, Satyaseelan

2012-03-01

Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patientsmore » were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.« less

Influence of transcutaneous electrical stimulation on heterotopic ossification: an experimental study in Wistar rats

PubMed Central

Zotz, T.G.G.; de Paula, J.B.

2015-01-01

Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues, resulting in joint mobility deficit and pain. Different treatment modalities have been tried to prevent HO development, but there is no consensus on a therapeutic approach. Since electrical stimulation is a widely used resource in physiotherapy practice to stimulate joint mobility, with analgesic and anti-inflammatory effects, its usefulness for HO treatment was investigated. We aimed to identify the influence of electrical stimulation on induced HO in Wistar rats. Thirty-six male rats (350-390 g) were used, and all animals were anesthetized for blood sampling before HO induction, to quantify the serum alkaline phosphatase. HO induction was performed by bone marrow implantation in both quadriceps of the animals, which were then divided into 3 groups: control (CG), transcutaneous electrical nerve stimulation (TENS) group (TG), and functional electrical stimulation (FES) group (FG) with 12 rats each. All animals were anesthetized and electrically stimulated twice per week, for 35 days from induction day. After this period, another blood sample was collected and quadriceps muscles were bilaterally removed for histological and calcium analysis and the rats were killed. Calcium levels in muscles showed significantly lower results when comparing TG and FG (P<0.001) and between TG and CG (P<0.001). Qualitative histological analyses confirmed 100% HO in FG and CG, while in TG the HO was detected in 54.5% of the animals. The effects of the muscle contractions caused by FES increased HO, while anti-inflammatory effects of TENS reduced HO. PMID:26292223

Inhalant abuse of 1,1-difluoroethane (DFE) leading to heterotopic ossification: a case report

PubMed Central

Little, Jill; Hileman, Barbara; Ziran, Bruce H

2008-01-01

Background Heterotopic ossification (HO) is the formation of mature, lamellar bone within soft tissues other than the periosteum. There are three recognized etiologies of HO: traumatic, neurogenic, and genetic. Presently, there are no definitively documented causal factors of HO. The following factors are presumed to place a patient at higher risk: 60 years of age or older, male, previous HO, hypertrophic osteoarthritis, ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, prior hip surgery, and surgical risk factors. Case presentation A 33-year-old male, involved in a motor vehicle crash, sustained an irreducible acetabulum fracture/dislocation, displaced proximal humerus fracture, and an impacted pilon fracture. During the time of injury, he was intoxicated from inhaling the aerosol propellant used in "dust spray" cans (1,1-difluoroethane, C2H4F2). Radiographs identified rapid pathologic bone formation about the proximal humeral metaphysis, proximal femur, elbow, and soft tissue several months following the initial injury. Discussion The patient did not have any genetic disorders that could have attributed to the bone formation but had some risk factors (male, fracture with dislocation). Surgically, the recommended precautions were followed to decrease the chance of HO. Although the patient did not have neurogenic injuries, the difluoroethane in dusting spray can cause damage to the central nervous system. Signals may have been mixed causing the patient's body to produce bone instead of tissue to strengthen the injured area. Conclusion What is unusual in this case is the rate at which the pathological bone formation appeared, which was long outside the 4–6 week window in which HO starts to appear. The authors are not certain as to the cause of this rapid formation but suspect that the patient's continued abuse of inhaled aerosol propellants may be the culprit. PMID:18973696

Inhalant abuse of 1,1-difluoroethane (DFE) leading to heterotopic ossification: a case report.

PubMed

Little, Jill; Hileman, Barbara; Ziran, Bruce H

2008-10-30

Heterotopic ossification (HO) is the formation of mature, lamellar bone within soft tissues other than the periosteum. There are three recognized etiologies of HO: traumatic, neurogenic, and genetic. Presently, there are no definitively documented causal factors of HO. The following factors are presumed to place a patient at higher risk: 60 years of age or older, male, previous HO, hypertrophic osteoarthritis, ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, prior hip surgery, and surgical risk factors. A 33-year-old male, involved in a motor vehicle crash, sustained an irreducible acetabulum fracture/dislocation, displaced proximal humerus fracture, and an impacted pilon fracture. During the time of injury, he was intoxicated from inhaling the aerosol propellant used in "dust spray" cans (1,1-difluoroethane, C2H4F2). Radiographs identified rapid pathologic bone formation about the proximal humeral metaphysis, proximal femur, elbow, and soft tissue several months following the initial injury. The patient did not have any genetic disorders that could have attributed to the bone formation but had some risk factors (male, fracture with dislocation). Surgically, the recommended precautions were followed to decrease the chance of HO. Although the patient did not have neurogenic injuries, the difluoroethane in dusting spray can cause damage to the central nervous system. Signals may have been mixed causing the patient's body to produce bone instead of tissue to strengthen the injured area. What is unusual in this case is the rate at which the pathological bone formation appeared, which was long outside the 4-6 week window in which HO starts to appear. The authors are not certain as to the cause of this rapid formation but suspect that the patient's continued abuse of inhaled aerosol propellants may be the culprit.

Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: a case-control analysis.

PubMed

Sheybani, Arshin; TenNapel, Mindi J; Lack, William D; Clerkin, Patrick; Hyer, Daniel E; Sun, Wenqing; Jacobson, Geraldine M

2014-07-01

To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). A matched case-control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not develop a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk of Radiation-Induced Malignancy With Heterotopic Ossification Prophylaxis: A Case–Control Analysis

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

Sheybani, Arshin, E-mail: arshin-sheybani@uiowa.edu; TenNapel, Mindi J.; Lack, William D.

2014-07-01

Purpose: To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). Methods and Materials: A matched case–control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not developmore » a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. Results: A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. Conclusion: We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not.« less

Do Postoperative Biomechanical Changes Induce Heterotopic Ossification After Cervical Arthroplasty?: A 5-Year Follow-up Study.

PubMed

Kim, Keun Su; Heo, Dong Hwa

2016-07-01

Prospective clinical study. To evaluate the factors that would predispose a patient to heterotopic ossification (HO) formation after cervical arthroplasty. HO after arthroplasty is one of the complications of cervical total disk replacement (TDR). However, the predisposing factors and pathophysiology of HO have not been precisely described. We prospectively enrolled and followed up 23 patients, who received single-level arthroplasty with ProDisc-C, for 5 years after the operation. The patients who developed grade 3 or 4 HO were classified into the "high-grade HO group," whereas the patients with grade 0, 1, or 2 HO were classified into the "low-grade HO group." We compared the postoperative changes in the range of motion (ROM) and height of the functional segmental unit (FSU) of the implantation segments between the 2 groups. The mean differences in height and ROM of the FSU were 2.59±1.42 mm and 6.7±3.2 degrees in the high-grade HO group, and 0.87±0.72 mm and 3.1±2.8 degrees in the low-grade HO group. The mean differences in height and ROM of the FSU were significantly higher in the high-grade HO group than in the low-grade HO group (P<0.05). After cervical arthroplasty, the height of the FSU and ROM of the implantation segments were significantly increased in the high-grade HO group compared with the low-grade HO group. Overcorrection of the height of the FSU and increase in the ROM of the implantation segment may influence the formation of HOs after cervical arthroplasty.

Difference in occurrence of heterotopic ossification according to prosthesis type in the cervical artificial disc replacement.

PubMed

Yi, Seong; Kim, Keung Nyun; Yang, Moon Sul; Yang, Joong Won; Kim, Hoon; Ha, Yoon; Yoon, Do Heum; Shin, Hyun Chul

2010-07-15

Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 +/- 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 +/- 7.4 months) than the other groups. Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study.

Effect of Naproxen Prophylaxis on Heterotopic Ossification Following Hip Arthroscopy: A Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Beckmann, James T; Wylie, James D; Potter, Michael Q; Maak, Travis G; Greene, Thomas H; Aoki, Stephen K

2015-12-16

Heterotopic ossification (HO) is a known complication of hip arthroscopy. Our objective was to determine the effect of postoperative naproxen therapy on the development of HO following arthroscopic surgery for femoroacetabular impingement. Between August 2011 and April 2013, 108 eligible patients were enrolled and randomized to take naproxen or a placebo for three weeks postoperatively. Radiographs were made at routine follow-up visits for one year following surgery. The primary outcome measure was the development of HO, as classified with the Brooker criteria and two-dimensional measurements on radiographs made at least seventy-five days postoperatively (average, 322 days). The primary analysis, performed with a Fisher exact test, compared the proportion of subjects with HO between the treatment and control groups. A single a priori interim analysis was planned at the midpoint of the study. Our data safety and monitoring board stopped this study when the interim analysis showed that the stopping criterion had been met for demonstration of efficacy of the naproxen intervention. The prevalence of HO was 46% (twenty-two of the forty-eight in the final analysis) in the placebo group versus 4% (two of forty-eight) in the naproxen group (p < 0.001). Medication compliance was 69% overall, but it did not differ between the naproxen and placebo groups. Minor adverse reactions to the study medications were reported in 42% of the patients taking naproxen versus 35% of those taking the placebo (p = 0.45). In this trial, prophylaxis with naproxen was effective in reducing the prevalence of HO without medication-related morbidity. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Shielding of the Hip Prosthesis During Radiation Therapy for Heterotopic Ossification is Associated with Increased Failure of Prophylaxis

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

Balboni, Tracy A.; Gaccione, Peter; Gobezie, Reuben

2007-04-01

Purpose: Radiation therapy (RT) is frequently administered to prevent heterotopic ossification (HO) after total hip arthroplasty (THA). The purpose of this study was to determine if there is an increased risk of HO after RT prophylaxis with shielding of the THA components. Methods and Materials: This is a retrospective analysis of THA patients undergoing RT prophylaxis of HO at Brigham and Women's Hospital between June 1994 and February 2004. Univariate and multivariate logistic regressions were used to assess the relationships of all variables to failure of RT prophylaxis. Results: A total of 137 patients were identified and 84 were eligiblemore » for analysis (61%). The median RT dose was 750 cGy in one fraction, and the median follow-up was 24 months. Eight of 40 unshielded patients (20%) developed any progression of HO compared with 21 of 44 shielded patients (48%) (p = 0.009). Brooker Grade III-IV HO developed in 5% of unshielded and 18% of shielded patients (p 0.08). Multivariate analysis revealed shielding (p = 0.02) and THA for prosthesis infection (p = 0.03) to be significant predictors of RT failure, with a trend toward an increasing risk of HO progression with age (p = 0.07). There was no significant difference in the prosthesis failure rates between shielded and unshielded patients. Conclusions: A significantly increased risk of failure of RT prophylaxis for HO was noted in those receiving shielding of the hip prosthesis. Shielding did not appear to reduce the risk of prosthesis failure.« less

Cancer risk estimates from radiation therapy for heterotopic ossification prophylaxis after total hip arthroplasty

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

Mazonakis, Michalis; Berris, Theoharris; Damilakis, John

2013-10-15

Purpose: Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty. This study was conducted to calculate the radiation dose to organs-at-risk and estimate the probability of cancer induction from radiotherapy for HO prophylaxis.Methods: Hip irradiation for HO with a 6 MV photon beam was simulated with the aid of a Monte Carlo model. A realistic humanoid phantom representing an average adult patient was implemented in Monte Carlo environment for dosimetric calculations. The average out-of-field radiation dose to stomach, liver, lung, prostate, bladder, thyroid, breast, uterus, and ovary was calculated. The organ-equivalent-dose to colon, that was partly included withinmore » the treatment field, was also determined. Organ dose calculations were carried out using three different field sizes. The dependence of organ doses upon the block insertion into primary beam for shielding colon and prosthesis was investigated. The lifetime attributable risk for cancer development was estimated using organ, age, and gender-specific risk coefficients.Results: For a typical target dose of 7 Gy, organ doses varied from 1.0 to 741.1 mGy by the field dimensions and organ location relative to the field edge. Blocked field irradiations resulted in a dose range of 1.4–146.3 mGy. The most probable detriment from open field treatment of male patients was colon cancer with a high risk of 564.3 × 10{sup −5} to 837.4 × 10{sup −5} depending upon the organ dose magnitude and the patient's age. The corresponding colon cancer risk for female patients was (372.2–541.0) × 10{sup −5}. The probability of bladder cancer development was more than 113.7 × 10{sup −5} and 110.3 × 10{sup −5} for males and females, respectively. The cancer risk range to other individual organs was reduced to (0.003–68.5) × 10{sup −5}.Conclusions: The risk for cancer induction from radiation therapy for HO prophylaxis after total hip arthroplasty varies considerably

Cancer risk estimates from radiation therapy for heterotopic ossification prophylaxis after total hip arthroplasty.

PubMed

Mazonakis, Michalis; Berris, Theoharris; Lyraraki, Efrossyni; Damilakis, John

2013-10-01

Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty. This study was conducted to calculate the radiation dose to organs-at-risk and estimate the probability of cancer induction from radiotherapy for HO prophylaxis. Hip irradiation for HO with a 6 MV photon beam was simulated with the aid of a Monte Carlo model. A realistic humanoid phantom representing an average adult patient was implemented in Monte Carlo environment for dosimetric calculations. The average out-of-field radiation dose to stomach, liver, lung, prostate, bladder, thyroid, breast, uterus, and ovary was calculated. The organ-equivalent-dose to colon, that was partly included within the treatment field, was also determined. Organ dose calculations were carried out using three different field sizes. The dependence of organ doses upon the block insertion into primary beam for shielding colon and prosthesis was investigated. The lifetime attributable risk for cancer development was estimated using organ, age, and gender-specific risk coefficients. For a typical target dose of 7 Gy, organ doses varied from 1.0 to 741.1 mGy by the field dimensions and organ location relative to the field edge. Blocked field irradiations resulted in a dose range of 1.4-146.3 mGy. The most probable detriment from open field treatment of male patients was colon cancer with a high risk of 564.3 × 10(-5) to 837.4 × 10(-5) depending upon the organ dose magnitude and the patient's age. The corresponding colon cancer risk for female patients was (372.2-541.0) × 10(-5). The probability of bladder cancer development was more than 113.7 × 10(-5) and 110.3 × 10(-5) for males and females, respectively. The cancer risk range to other individual organs was reduced to (0.003-68.5) × 10(-5). The risk for cancer induction from radiation therapy for HO prophylaxis after total hip arthroplasty varies considerably by the treatment parameters, organ site in respect to treatment volume and patient

Risk Factors for the Development of Heterotopic Ossification in Seriously Burned Adults: A NIDRR Burn Model System Database Analysis

PubMed Central

Levi, Benjamin; Jayakumar, Prakash; Giladi, Avi; Jupiter, Jesse B.; Ring, David C.; Kowalske, Karen; Gibran, Nicole S.; Herndon, David; Schneider, Jeffrey C.; Ryan, Colleen M.

2015-01-01

Purpose Heterotopic ossification (HO) is a debilitating complication of burn injury; however, incidence and risk factors are poorly understood. In this study we utilize a multicenter database of adults with burn injuries to identify and analyze clinical factors that predict HO formation. Methods Data from 6 high-volume burn centers, in the Burn Injury Model System Database, were analyzed. Univariate logistic regression models were used for model selection. Cluster-adjusted multivariate logistic regression was then used to evaluate the relationship between clinical and demographic data and the development of HO. Results Of 2,979 patients in the database with information on HO that addressed risk factors for development of HO, 98 (3.5%) developed HO. Of these 98 patients, 97 had arm burns, and 96 had arm grafts. Controlling for age and sex in a multivariate model, patients with >30% total body surface area (TBSA) burn had 11.5x higher odds of developing HO (p<0.001), and those with arm burns that required skin grafting had 96.4x higher odds of developing HO (p=0.04). For each additional time a patient went to the operating room, odds of HO increased 30% (OR 1.32, p<0.001), and each additional ventilator day increase odds 3.5% (OR 1.035, p<0.001). Joint contracture, inhalation injury, and bone exposure did not significantly increase odds of HO. Conclusion Risk factors for HO development include >30% TBSA burn, arm burns, arm grafts, ventilator days, and number of trips to the operating room. Future studies can use these results to identify highest-risk patients to guide deployment of prophylactic and experimental treatments. PMID:26496115

Heterotopic pregnancy following induction of ovulation with clomiphene citrate

PubMed Central

Ghandi, Sedigheh; Ahmadi, Raheleh; Fazel, Mahmoud

2011-01-01

Background: Although heterotopic gestation is common in assisted reproductive techniques, it is very rare in natural conception and clomiphene induced pregnancy. Diagnosis and appropriate intervention of heterotopic pregnancy requires a high index of suspicious. Case: In this paper a case of heterotopic pregnancy in a 30-year old woman with hemoperitoneum from ruptured tubal pregnancy with live intrauterine gestation at 9 weeks of gestation is reported. Conclusion: This case suggests that a heterotopic pregnancy must always be considered particularly after the induction of ovulation by clomiphene citrate or assisted reproductive technology. Every clinician treating women of reproductive age should keep this diagnosis in mind. It also demonstrates that early diagnosis is essential in order to salvage the intrauterine pregnancy and avoid maternal morbidity and mortality. PMID:26396583

Heterotopic pregnancy following induction of ovulation with clomiphene citrate.

PubMed

Ghandi, Sedigheh; Ahmadi, Raheleh; Fazel, Mahmoud

2011-01-01

Although heterotopic gestation is common in assisted reproductive techniques, it is very rare in natural conception and clomiphene induced pregnancy. Diagnosis and appropriate intervention of heterotopic pregnancy requires a high index of suspicious. In this paper a case of heterotopic pregnancy in a 30-year old woman with hemoperitoneum from ruptured tubal pregnancy with live intrauterine gestation at 9 weeks of gestation is reported. This case suggests that a heterotopic pregnancy must always be considered particularly after the induction of ovulation by clomiphene citrate or assisted reproductive technology. Every clinician treating women of reproductive age should keep this diagnosis in mind. It also demonstrates that early diagnosis is essential in order to salvage the intrauterine pregnancy and avoid maternal morbidity and mortality.

Heterotopic Pancreas: Histopathologic Features, Imaging Findings, and Complications.

PubMed

Rezvani, Maryam; Menias, Christine; Sandrasegaran, Kumaresan; Olpin, Jeffrey D; Elsayes, Khaled M; Shaaban, Akram M

2017-01-01

Heterotopic pancreas is a congenital anomaly in which pancreatic tissue is anatomically separate from the main gland. The most common locations of this displacement include the upper gastrointestinal tract-specifically, the stomach, duodenum, and proximal jejunum. Less common sites are the esophagus, ileum, Meckel diverticulum, biliary tree, mesentery, and spleen. Uncomplicated heterotopic pancreas is typically asymptomatic, with the lesion being discovered incidentally during an unrelated surgery, during an imaging examination, or at autopsy. The most common computed tomographic appearance of heterotopic pancreas is that of a small oval intramural mass with microlobulated margins and an endoluminal growth pattern. The attenuation and enhancement characteristics of these lesions parallel their histologic composition. Acinus-dominant lesions demonstrate avid homogeneous enhancement after intravenous contrast material administration, whereas duct-dominant lesions are hypovascular and heterogeneous. At magnetic resonance imaging, the heterotopic pancreas is isointense to the orthotopic pancreas, with characteristic T1 hyperintensity and early avid enhancement after intravenous gadolinium-based contrast material administration. Heterotopic pancreatic tissue has a rudimentary ductal system in which an orifice is sometimes visible at imaging as a central umbilication of the lesion. Complications of heterotopic pancreas include pancreatitis, pseudocyst formation, malignant degeneration, gastrointestinal bleeding, bowel obstruction, and intussusception. Certain complications may be erroneously diagnosed as malignancy. Paraduodenal pancreatitis is thought to be due to cystic degeneration of heterotopic pancreatic tissue in the medial wall of the duodenum. Recognizing the characteristic imaging features of heterotopic pancreas aids in differentiating it from cancer and thus in avoiding unnecessary surgery. © RSNA, 2017.

Do inflammatory markers portend heterotopic ossification and wound failure in combat wounds?

PubMed

Forsberg, Jonathan A; Potter, Benjamin K; Polfer, Elizabeth M; Safford, Shawn D; Elster, Eric A

2014-09-01

After a decade of war in Iraq and Afghanistan, we have observed an increase in combat-related injury survival and a paradoxical increase in injury severity, mainly because of the effects of blasts. These severe injuries have a devastating effect on each patient's immune system resulting in massive upregulation of the systemic inflammatory response. By examining inflammatory mediators, preliminary data suggest that it may be possible to correlate complications such as wound failure and heterotopic ossification (HO) with distinct systemic and local inflammatory profiles, but this is a relatively new topic. We asked whether systemic or local markers of inflammation could be used as an objective means, independent of demographic and subjective factors, to estimate the likelihood of (1) HO and/or (2) wound failure (defined as wounds requiring surgical débridement after definitive closure, or wounds that were not closed or covered within 21 days of injury) in patients sustaining combat wounds. Two hundred combat wounded active-duty service members who sustained high-energy extremity injuries were prospectively enrolled between 2008 and 2012. Of these 200 patients, 189 had adequate followups to determine the presence or absence of HO, and 191 had adequate followups to determine the presence or absence of wound failure. In addition to injury-specific and demographic data, we quantified 24 cytokines and chemokines during each débridement. Patients were followed clinically for 6 weeks, and radiographs were obtained 3 months after definitive wound closure. Associations were investigated between these markers and wound failure or HO, while controlling for known confounders. The presence of an amputation (p < 0.001; odds ratio [OR], 6.1; 95% CI. 1.63-27.2), Injury Severity Score (p = 0.002; OR, 33.2; 95% CI, 4.2-413), wound surface area (p = 0.001; OR, 1.01; 95% CI, 1.002-1.009), serum interleukin (IL)-3 (p = 0.002; OR, 2.41; 95% CI, 1.5-4.5), serum IL-12p70 (p = 0.01; OR, 0

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2016-12-01

lamellar bone within soft tissue after severe traumatic in- jury [10]. It is known to develop in the majority of combat- related amputations, and early...in- jury pattern alone and in various combinations. Lastly, we evaluated the time course of gene expression for a small subset of genes at given...demonstrated in a murine Achilles tenotomy plus partial-thickness dorsum burn in- jury model that injured mice develop endochondral ectopic bone and

Skeletal development in the African elephant and ossification timing in placental mammals

PubMed Central

Hautier, Lionel; Stansfield, Fiona J.; Allen, W. R. Twink; Asher, Robert J.

2012-01-01

We provide here unique data on elephant skeletal ontogeny. We focus on the sequence of cranial and post-cranial ossification events during growth in the African elephant (Loxodonta africana). Previous analyses on ossification sequences in mammals have focused on monotremes, marsupials, boreoeutherian and xenarthran placentals. Here, we add data on ossification sequences in an afrotherian. We use two different methods to quantify sequence heterochrony: the sequence method and event-paring/Parsimov. Compared with other placentals, elephants show late ossifications of the basicranium, manual and pedal phalanges, and early ossifications of the ischium and metacarpals. Moreover, ossification in elephants starts very early and progresses rapidly. Specifically, the elephant exhibits the same percentage of bones showing an ossification centre at the end of the first third of its gestation period as the mouse and hamster have close to birth. Elephants show a number of features of their ossification patterns that differ from those of other placental mammals. The pattern of the initiation of the ossification evident in the African elephant underscores a possible correlation between the timing of ossification onset and gestation time throughout mammals. PMID:22298853

Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip joints: is there a risk for radiation-induced malignancies?

PubMed

Berris, Theocharis; Mazonakis, Michalis; Kachris, Stefanos; Damilakis, John

2014-05-01

Radiotherapy, used for heterotopic ossification (HO) management, may increase radiation risk to patients. This study aimed to determine the peripheral dose to radiosensitive organs and the associated cancer risks due to radiotherapy of HO in common non-hip joints. A Monte Carlo model of a medical linear accelerator combined with a mathematical phantom representing an average adult patient were employed to simulate radiotherapy for HO with standard AP and PA fields in the regions of shoulder, elbow and knee. Radiation dose to all out-of-field radiosensitive organs defined by the International Commission on Radiological Protection was calculated. Cancer induction risk was estimated using organ-specific risk coefficients. Organ dose change with increased field dimensions was also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of shoulder, elbow and knee, resulted in the following equivalent organ dose ranges of 0.85-62 mSv, 0.28-1.6 mSv and 0.04-1.6 mSv, respectively. Respective ranges for cancer risk were 0-5.1, 0-0.6 and 0-1.3 cases per 10(4) persons. Increasing the field size caused an average increase of peripheral doses by 15-20%. Individual organ dose increase depends upon the primary treatment site and the distance between organ of interest and treatment volume. Relatively increased risks of more than 1 case per 10,000 patients were found for skin, breast and thyroid malignancies after treatment in the region of shoulder and for skin cancer following elbow irradiation. The estimated risk for inducing any other malignant disease ranges from negligible to low. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A preliminary investigation on the effect of extracorporeal shock wave therapy as a treatment for neurogenic heterotopic ossification following traumatic brain injury. Part II: Effects on function.

PubMed

Reznik, J E; Biros, E; Sacher, Y; Kibrik, O; Milanese, S; Gordon, S; Galea, M P

2017-01-01

Neurogenic heterotopic ossification (NHO) occurs as a complication of traumatic brain injury (TBI). Management of clinically significant NHO remains variable. Complications of mature NHO include limitation of mobility. The effect of the extracorporeal shock wave therapy (ESWT) on range of motion at hip and knee, and function in patients with TBI with chronic NHO was investigated. A series of single-case studies applying ESWT to chronic NHO at the hip or knee of 11 patients with TBI were undertaken at a rehabilitation hospital. Participants received four applications of high-energy EWST delivered to the affected hip or knee over a period of 8 weeks. Two-weekly follow- up assessments were carried out; final assessments were made 3 and 6 months post-intervention. Range of motion (ROM) and Functional Reach (FR) or Modified Functional Reach (MFR) were measured. Application of high-energy ESWT was associated with significant improvement in ROM (flexion) of the NHO-affected knee (Tau = 0.833, 95% CI 0.391-1.276, p = 0.002) and significant improvement of FR (Overall Tau 0.486, 95% CI 0.141-0.832, p = 0.006); no significant improvement in hip ROM or MFR. ESWT may improve mobility and balance of patients with TBI who have chronic NHO.

Spontaneous Heterotopic Pregnancy: Dual Case Report and Review of Literature.

PubMed

Chadee, Annika; Rezai, Shadi; Kirby, Catherine; Chadwick, Ekaterina; Gottimukkala, Sri; Hamaoui, Abraham; Stankovich, Vasiliy; Hale, Theodore; Gilak, Hamid; Momtaz, Mohammad; Sasken, Harvey; Henderson, Cassandra E

2016-01-01

Introduction. Heterotopic pregnancy is a rare complication usually seen in populations at risk for ectopic pregnancy or those undergoing fertility treatments. It is a potentially dangerous condition occurring in only 1 in 30,000 spontaneous pregnancies. With the advent of Assisted Reproduction Techniques (ART) and ovulation induction, the overall incidence of heterotopic pregnancy has risen to approximately 1 in 3,900 pregnancies. Other risk factors include a history of pelvic inflammatory disease (PID), tubal damage, pelvic surgery, uterine Mullerian abnormalities, and prior tubal surgery. Heterotopic pregnancy is a potentially fatal condition, rarely occurring in natural conception cycles. Most commonly, heterotopic pregnancy is diagnosed at the time of rupture when surgical management is required. Case. This paper represents two cases of heterotopic pregnancies as well as a literature review. Conclusion. Heterotopic pregnancy should be suspected in patients with an adnexal mass, even in the absence of risk factors. Clinicians must be alert to the fact that confirming an intrauterine pregnancy clinically or by ultrasound does not exclude the coexistence of an ectopic pregnancy. A high index of suspicion in women is needed for early and timely diagnosis, and management with laparotomy or laparoscopy can result in a favorable and successful obstetrical outcome.

Delivery of siRNA Silencing Runx2 Using a Multifunctional Polymer-Lipid Nanoparticle Inhibits Osteogenesis in a Cell Culture Model of Heterotopic Ossification

PubMed Central

Mishra, Swati; Vaughn, Asa D.; Devore, David I.

2015-01-01

Heterotopic ossification (HO) associated with traumatic neurological or musculoskeletal injuries remains a major clinical challenge. One approach to understanding better and potentially treating this condition is to silence one or more genes believed to be responsible for osteogenesis by small interfering RNA (siRNA) post-injury. Improved methods of delivering siRNA to myoprogenitor cells as well as relevant cell culture models of HO are needed to advance this approach. We utilize a model of HO featuring C2C12 myoprogenitor cells stimulated to the osteogenic phenotype by addition of BMP-2. For siRNA delivery, we utilize a nanocomposite consisting of DOTAP- based cationic liposomes coated with a graft copolymer of poly(propylacrylic acid) grafted with polyetheramine (Jeffamine), as this system has been shown previously to deliver antisense oligonucleotides safely into cells and out of endosomes for gene silencing in vitro and in vivo. Delivery of siRNA targeting Runx2, a transcription factor downstream of BMP-2, to stimulated C2C12 cells produced greater than 60% down-regulation of the Runx2 gene. This level of gene silencing was sufficient to inhibit alkaline phosphatase activity over the course of several days and calcium phosphate deposition over the course of 2 weeks. These results show the utility of the BMP-2/C2C12 model for capturing the cellular cell-fate decision in HO. Further, they suggest DOTAP/PPAA-g-Jeffamine as a promising delivery system for siRNA– based therapy for HO. PMID:23146945

A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds.

PubMed

Knoll, Fabien; Chiappe, Luis M; Sanchez, Sophie; Garwood, Russell J; Edwards, Nicholas P; Wogelius, Roy A; Sellers, William I; Manning, Phillip L; Ortega, Francisco; Serrano, Francisco J; Marugán-Lobón, Jesús; Cuesta, Elena; Escaso, Fernando; Sanz, Jose Luis

2018-03-05

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.

A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds

DOE PAGES

Knoll, Fabien; Chiappe, Luis M.; Sanchez, Sophie; ...

2018-03-05

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages ofmore » development. Finally, comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.« less

A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds

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

Knoll, Fabien; Chiappe, Luis M.; Sanchez, Sophie

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages ofmore » development. Finally, comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.« less

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2016-12-01

the study for the presence or absence of ectopic bone formation at the indicated time points post injury (Table 1.). 8 Table 1. Incidence of HO at...7, 10, 14, and 21 days post injury 42 Palovarotene Suppresses Early Chondrogenic and Osteogenic Differentiation In this set of studies we...using MicroCT imaging to quantitate total new bone and ectopic bone (non-associated with cortical margins) volume. In a second study arm, serum was

Leptin increases growth of primary ossification centers in fetal mice

PubMed Central

Bertoni, Laura; Ferretti, Marzia; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Benelli, Augusta; Palumbo, Carla

2009-01-01

The effect of peripheral leptin on fetal primary ossification centers during the early phases of bone histogenesis was investigated by administration of leptin to pregnant mice. Fourteen pregnant mice were divided into two groups. The treated pregnant group was subcutaneously injected in the intrascapular region with supraphysiologic doses (2 mg kg−1) of leptin (Vinci Biochem, Firenze, Italy) in a volume of 0.1 mL per 10 g body weight, at the 7th, 9th and 11th day of gestation. The control group was treated with physiological solution in the same manner and same times as the treated group. The new-born mice were killed 1 day after birth and the primary ossification centers were stained with Alizarin Red S after diaphanizing the soft tissues in 1% potassium hydroxide. The development of both endochondral and intramembranous ossification centers was morphometrically analysed in long bones. The results showed that the ossification centers of mice born by mothers treated with leptin grow more rapidly in both length and cross-sectional area compared with mice born by the untreated mothers. As the development of long bones depends on endochondral ossification occurring at proximal and distal epiphyseal plates as well as on intramembranous ossification along the periosteal surface, it appears that leptin activates the differentiation and proliferation of both chondrocytes and osteoblasts. The role of leptin as a growth factor of cartilage and bone is discussed in the light of the data reported in the literature. PMID:19682137

Jagged1 is essential for osteoblast development during maxillary ossification

PubMed Central

Hill, Cynthia R.; Yuasa, Masato; Schoenecker, Jonathan; Goudy, Steven L.

2015-01-01

Maxillary hypoplasia occurs due to insufficient maxillary intramembranous ossification, leading to poor dental occlusion, respiratory obstruction and cosmetic deformities. Conditional deletion of Jagged1 (Jag1) in cranial neural crest (CNC) cells using Wnt1-cre; Jagged1f/f (Jag1CKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using μCT evaluation. Jag1CKO maxillas had altered collagen deposition, delayed ossification, and reduced expression of early and late determinants of osteoblast development during maxillary ossification. In vitro bone cultures on Jag1CKO mouse embryonic maxillary mesenchymal (MEMM) cells demonstrated decreased mineralization that was also associated with diminished induction of osteoblast determinants. BMP receptor expression was dysregulated in the Jag1CKO MEMM cells suggesting that these cells were unable to respond to BMP-induced differentiation. JAG1-Fc rescued in vitro mineralization and osteoblast gene expression changes. These data suggest that JAG1 signaling in CNC-derived MEMM cells is required for osteoblast development and differentiation during maxillary ossification. PMID:24491691

Risk factors for the development of heterotopic ossification in seriously burned adults: A National Institute on Disability, Independent Living and Rehabilitation Research burn model system database analysis.

PubMed

Levi, Benjamin; Jayakumar, Prakash; Giladi, Avi; Jupiter, Jesse B; Ring, David C; Kowalske, Karen; Gibran, Nicole S; Herndon, David; Schneider, Jeffrey C; Ryan, Colleen M

2015-11-01

Heterotopic ossification (HO) is a debilitating complication of burn injury; however, incidence and risk factors are poorly understood. In this study, we use a multicenter database of adults with burn injuries to identify and analyze clinical factors that predict HO formation. Data from six high-volume burn centers, in the Burn Injury Model System Database, were analyzed. Univariate logistic regression models were used for model selection. Cluster-adjusted multivariate logistic regression was then used to evaluate the relationship between clinical and demographic data and the development of HO. Of 2,979 patients in the database with information on HO that addressed risk factors for development of HO, 98 (3.5%) developed HO. Of these 98 patients, 97 had arm burns, and 96 had arm grafts. When controlling for age and sex in a multivariate model, patients with greater than 30% total body surface area burn had 11.5 times higher odds of developing HO (p < 0.001), and those with arm burns that required skin grafting had 96.4 times higher odds of developing HO (p = 0.04). For each additional time a patient went to the operating room, odds of HO increased by 30% (odds ratio, 1.32; p < 0.001), and each additional ventilator day increased odds by 3.5% (odds ratio, 1.035; p < 0.001). Joint contracture, inhalation injury, and bone exposure did not significantly increase odds of HO. Risk factors for HO development include greater than 30% total body surface area burn, arm burns, arm grafts, ventilator days, and number of trips to the operating room. Future studies can use these results to identify highest-risk patients to guide deployment of prophylactic and experimental treatments. Prognostic study, level III.

Uncovertebral hypertrophy is a significant risk factor for the occurrence of heterotopic ossification after cervical disc replacement: survivorship analysis of Bryan disc for single-level cervical arthroplasty.

PubMed

Chung, Sang-Bong; Muradov, Johongir M; Lee, Sun-Ho; Eoh, Whan; Kim, Eun-Sang

2012-06-01

The purpose of this study is to investigate the incidence of heterotopic ossification (HO) in the Bryan cervical arthroplasty group and to identify associations between preoperative factors and the development of HO. We performed a retrospective review of clinical and radiological data on patients who underwent single-level cervical arthroplasty with Bryan prosthesis between January 2005 and September 2007. Patients were postoperatively followed-up at 1, 3, 6, 12 months and every year thereafter. The clinical assessment was conducted using Odom's criteria. The presence of HO was evaluated on the basis of X-ray at each time-point according to the McAfee classification. In this study, we focused on survivorship of Bryan prosthesis for single-level arthroplasty. The occurrence of ROM-affecting HO was defined as a functional failure and was used as an endpoint for determining survivorship. Through the analysis of 19 cases of Bryan disc arthroplasty for cervical radiculopathy and/or myelopathy, we revealed that ROM-affecting HO occurs in as many as 36.8% of cases and found that 37% of patients had ROM-affecting HO within 24 months following surgery. The overall survival time to the occurrence of ROM-affecting HO was 36.4 ± 4.4 months. Survival time of the prosthesis in the patient group without preoperative uncovertebral hypertrophy was significantly longer than that in the patient group with preoperative uncovertebral hypertrophy (47.2 months vs 25.5 months, p = 0.02). Cox regression proportional hazard analysis illustrated that preoperative uncovertebral hypertrophy was determined as a significant risk factor for the occurrence of ROM-affecting HO (hazard ratio = 12.30; 95% confidential interval = 1.10-137.03; p = 0.04). These findings suggest that the condition of the uncovertebral joint must be evaluated in preoperative planning for Bryan cervical arthroplasty.

Early Detection of Heterotopic Ossification for Effective Prevention and Treatment

DTIC Science & Technology

2014-04-01

selectively induced in rat model of myocardial infarction . Inflammation. 2001;25(5):293-300. 20. Tögel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF...the development of HO, subtle muscle injuries could trigger SDF-1 build-up locally and MSC recruitment. This project is based on a hypothesis that

Asymmetric C7 pedicle subtraction osteotomy for correction of rigid cervical coronal imbalance secondary to post-traumatic heterotopic ossification: a case report, description of a novel surgical technique, and literature review.

PubMed

Theologis, Alexander A; Bellevue, Kate D; Qamirani, Erion; Ames, Christopher P; Deviren, Vedat

2017-05-01

Deformities of the cervical spine are uncommon in the coronal plane. In this report, a unique case of a 31-year-old male with a fixed, 30° left coronal deformity due to heterotopic ossification 3 years status post poly-trauma was treated with an asymmetric C7 pedicle subtraction osteotomy (PSO). Case report. Pre-operatively, the patient had a fixed 45-degree left tilt of his neck and radiographs demonstrated a rigid 30° scoliosis, 7 cm coronal imbalance, and 4 cm negative sagittal balance, diffuse bridging bone between the spinous processes and the facet joints of C5 to T1 bilaterally. An asymmetric C7 PSO with C2-T3 posterior spinal fusion was completed without complication. There was residual 9° coronal deformity, 2.9 cm left coronal imbalance, and 2.3 cm sagittal imbalance. He had a marked improvement in his function, as assessed by the SF-36 physical component score (pre-op 31.1; post-op 44.7) and mental component score (pre-op 46.0; post-op 66.8). Post-operatively, neck disability index scores also improved (pre-op 38; post-op 16). Although the patient passed away from a drug overdose 14 months post-operatively, he did not report neck pain, he had not sought evaluation from another physician for his neck, and he had not undergone a subsequent neck operation before his passing. In this one patient, an asymmetric C7 PSO was performed safely. While it was effective in addressing a fixed cervical coronal imbalance, its efficacy and safety profile should be confirmed in larger cohorts.

Heterotopic pancreas in excluded stomach diagnosed after gastric bypass surgery

PubMed Central

2013-01-01

Background Heterotopic pancreas is defined as finding of pancreatic tissue without anatomic and vascular continuity with the normal pancreas. Heterotopic pancreas is a rare condition difficult to diagnose and with controversial clinical management. Case presentation We describe a 43 year old female patient previously submitted to laparoscopic gastric bypass for primary treatment of morbid obesity; 5 years later, the patient was discovered to have a mass in the antrum of the excluded stomach that was found to be heterotopic pancreatic tissue. Before gastric bypass surgery, the presence of the pancreatic mass in the gastric wall was unnoticed in the imagiologic records. Conclusion This is the first reported case of pancreatic heterotopy diagnosed in the excluded stomach after gastric bypass. A putative role of incretin hormones in mediating pancreatic cell hyperplasia of heterotopic pancreatic remnants should be considered an additional hypothesis that requires further research. PMID:24267291

Ossification center of the infant hip: sonographic and radiographic correlation.

PubMed

Harcke, H T; Lee, M S; Sinning, L; Clarke, N M; Borns, P F; MacEwen, G D

1986-08-01

A new sonographic technique for evaluating the ossification center of the infant's hip allowed identification of the ossific nucleus before it could be visualized radiographically. With this technique, delay in ossification associated with hip pathology can also be recognized. Proper assessment of the size of the ossific nucleus requires scanning in orthogonal planes. Acoustic shadowing causes the growing ossification center to appear curved and may make the medial acetabulum and triradiate cartilage difficult to identify. Sonographic hip evaluation usually ceases to be reliable in children over 1 year old.

Blast Injuries And Heterotopic Ossification

DTIC Science & Technology

2012-08-01

transfemoral amputation. Note the skin graft over the terminal portion of the residual limb. Although we advocate avoiding terminal skin grafting of...of the overlying skin graft . Fig. 2a 177 K. A. ALFIERI, J. A. FORSBERG, B. K. POTTER BONE & JOINT RESEARCH mimimum of six months prior to performing

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2015-10-01

plastic cages and kept on a 12-hour light/dark cycle with unlimited access to food (standard rodent chow) and freshwater ad libitum. The study protocol (12...osteogenic mediators, we further propose that initiation of prophylactic local and/or systemicGram-positive antimicrobial therapy at the time of injury and...polymicrobial infections, impact of differential TLR signaling, and the evaluation of systemic and/or local antimicrobial in- terventions, is necessary

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2014-10-01

arthroplasty . There is also a congenital form of it that can affect children and young adults. Surgery is often used to remove the HO lesions, but this...in patients undergoing invasive surgeries such as total hip arthroplasty (6). However, HO is more common in our wounded service-members than it

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2015-10-01

in the general population undergoing invasive surgeries such as total hip arthroplasty . There is also a congenital form of it that can affect...insults and can also occur in patients undergoing invasive surgeries, including total hip arthroplasty (6). HO is very common in our wounded service

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2014-10-01

Resistant Staphylococcus Aureus ( MRSA ) being the most common isolate from combat wounds. To more precisely identify the cellular and molecular changes...Resistant Staphylococcus Aureus ( MRSA ) infection on the rate development and severity of HO formation. Results, Progress and Accomplishments with...10CFUs of a highly virulent strain of either Acinetobacter Baumannii or Methicillin Resistant Staphylococcus Aureus ( MRSA ) which were isolated from

Delayed endochondral ossification in early medial coronoid disease (MCD): a morphological and immunohistochemical evaluation in growing Labrador retrievers.

PubMed

Lau, S F; Hazewinkel, H A W; Grinwis, G C M; Wolschrijn, C F; Siebelt, M; Vernooij, J C M; Voorhout, G; Tryfonidou, M A

2013-09-01

Medial coronoid disease (MCD) is a common joint disease of dogs. It has a multifactorial aetiology, but the relationship between known causal factors and the disease has yet to be elucidated. As most of the published literature is clinical and it reports changes associated with advanced disease, it is not known whether the changes reflect the cause or consequences of the condition. The aim of this study was to investigate early micromorphological changes occurring in articular cartilage and to describe the postnatal development of the medial coronoid process (MCP) before MCD develops. Three litters of MCD-prone young Labrador retrievers were purpose-bred from a dam and two sires with MCD. Comparisons of the micromorphological appearance of the MCP in MCD-negative and MCD-positive joints demonstrated that MCD was initially associated with a disturbance of endochondral ossification, namely a delay in the calcification of the calcifying zone, without concurrent abnormalities in the superficial layers of the joint cartilage. Cartilage canals containing patent blood vessels were only detected in dogs <12 weeks old, but the role of these channels in impaired ossification requires further investigation. Retained hyaline cartilage might ossify as the disease progresses, but weak areas can develop into cracks between the retained cartilage and the subchondral bone, leading to cleft formation and fragmentation of the MCP. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intrahepatic peribiliary perivascular epithelioid cell tumor (PEComa) associated with heterotopic pancreas: A case report.

PubMed

Kiriyama, Yuka; Tsukamoto, Tetsuya; Mizoguchi, Yoshikazu; Ishihara, Shin; Horiguchi, Akihiko; Tokoro, Takamasa; Kato, Yutaro; Sugioka, Atsushi; Kuroda, Makoto

2016-08-20

Perivascular epithelioid-cell tumor (PEComa) is a group of rare mesenchymal neoplasms that express myomelanocytic-cell markers and exhibit a wide variety of histopathological features. Although heterotopic pancreas has been reported to occur in the gastrointestinal tract, intrahepatic heterotopic pancreas has been reported only rarely. We present a case of intrahepatic PEComa that showed a strong regional correlation with the presence of heterotopic pancreas. An intrahepatic tumor and biliary dilatation was incidentally discovered during a diagnostic evaluation to investigate low-back pain in a 47-year-old Japanese male. Cholangiocarcinoma was suspected and a left hemihepatectomy performed. Histological examination revealed a 3 × 3.8-mm tumor in the neighboring B2 bile duct. Histological and immunohistochemical investigations revealed the presence of a PEComa and pancreatic acini within the tumor mass. PEComa in the hepatobiliary and pancreatic regions are extremely rare. The presence of heterotopic pancreas is also relatively uncommon. The strong regional association of these 2 lesions raises the possibility of a PEComa originating from heterotopic pancreas or from an irritable response caused by heterotopic pancreas.

Indian hedgehog signaling promotes chondrocyte differentiation in enchondral ossification in human cervical ossification of the posterior longitudinal ligament.

PubMed

Sugita, Daisuke; Yayama, Takafumi; Uchida, Kenzo; Kokubo, Yasuo; Nakajima, Hideaki; Yamagishi, Atsushi; Takeura, Naoto; Baba, Hisatoshi

2013-10-15

Histological, immunohistochemical, and immunoblot analyses of the expression of Indian hedgehog (Ihh) signaling in human cervical ossification of the posterior longitudinal ligament (OPLL). To examine the hypothesis that Ihh signaling in correlation with Sox9 and parathyroid-related peptide hormone (PTHrP) facilitates chondrocyte differentiation in enchondral ossification process in human cervical OPLL. In enchondral ossification, certain transcriptional factors regulate cell differentiation. OPLL is characterized by overexpression of these factors and disturbance of the normal cell differentiation process. Ihh signaling is essential for enchondral ossification, especially in chondrocyte hypertrophy. Samples of ossified ligaments were harvested from 45 patients who underwent anterior cervical decompressive surgery for symptomatic OPLL, and 6 control samples from patients with cervical spondylotic myelopathy/radiculopathy without OPLL. The harvested sections were stained with hematoxylin-eosin and toluidine blue, examined by transmission electron microscopy, and immunohistochemically stained for Ihh, PTHrP, Sox9, type X, XI collagen, and alkaline phosphatase. Immunoblot analysis was performed in cultured cells derived from the posterior longitudinal ligaments in the vicinity of the ossified plaque and examined for the expression of these factors. The ossification front in OPLL contained chondrocytes at various differentiation stages, including proliferating chondrocytes in fibrocartilaginous area, hypertrophic chondrocytes around the calcification front, and apoptotic chondrocytes near the ossified area. Immunoreactivity for Ihh and Sox9 was evident in proliferating chondrocytes and was strongly positive for PTHrP in hypertrophic chondrocytes. Mesenchymal cells with blood vessel formation were positive for Ihh, PTHrP, and Sox9. Cultured cells from OPLL tissues expressed significantly higher levels of Ihh, PTHrP, and Sox9 than those in non-OPLL cells. Our results

Developing a toolbox for analysis of warrior wound biopsies: vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Crane, Nicole J.; O'Brien, Frederick P.; Forsberg, Jonathan A.; Potter, Benjamin K.; Elster, Eric A.

2011-03-01

The management of modern traumatic war wounds remains a significant challenge for clinicians. This is a reflection of the extensive osseous and soft-tissue damage caused by blasts and high-energy projectiles. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjectively based. Some wounds require an extended period of time to close or fail to remain closed, despite the use and application of novel wound-specific treatment modalities. Aside from impaired wound healing, additional wound complications include wound infection, biofilm formation, and heterotopic ossification (the pathological mineralization of soft tissues). An understanding of the molecular environment of acute wounds throughout the debridement process can provide valuable insight into the mechanisms associated with the eventual wound outcome. The analysis of Raman spectra of ex vivo wound biopsy tissue obtained from serial traumatic wound debridements reveals a decreased 1665 cm-1/1445 cm-1 band area ratio in impaired healing wounds, indicative of an impaired remodeling process, in addition to a decreased 1240 cm-1/1270cm-1. The examination of debrided tissue exhibits mineralization during the early development of heterotopic ossification. Finally, preliminary results suggest that Fourier transform infrared (FT-IR) images of wound effluent may be able to provide early microbiological information about the wound.

Insulin antagonises pigment epithelium-derived factor (PEDF)-induced modulation of lineage commitment of myocytes and heterotrophic ossification.

PubMed

Carnagarin, Revathy; Elahy, Mina; Dharmarajan, Arun M; Dass, Crispin R

2017-12-16

Extensive bone defects arising as a result of trauma, infection and tumour resection and other bone pathologies necessitates the identification of effective strategies in the form of tissue engineering, gene therapy and osteoinductive agents to enhance the bone repair process. PEDF is a multifunctional glycoprotein which plays an important role in regulating osteoblastic differentiation and bone formation. PEDF treatment of mice and human skeletal myocytes at physiological concentration inhibited myogenic differentiation and activated Erk1/2 MAPK- dependent osteogenic transdifferentiation of myocytes. In mice, insulin, a promoter of bone regeneration, attenuated PEDF-induced expression of osteogenic markers such as osteocalcin, alkaline phosphatase and mineralisation for bone formation in the muscle and surrounding adipose tissue. These results provide new insights into the molecular aspects of the antagonising effect of insulin on PEDF-dependent modulation of the differentiation commitment of musculoskeletal environment into osteogenesis, and suggest that PEDF may be developed as an effective clinical therapy for bone regeneration as its heterotopic ossification can be controlled via co-administration of insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

Heterotopic synaptic bodies in the auditory hair cells of adult lizards.

PubMed

Miller, M R; Beck, J

1987-07-01

The auditory hair cells of adults of eight species of lizards (three gekkonids: Coleonyx variegatus, Gekko gecko, and Cosymbotus platyurus; two teiids: Ameiva ameiva and Cnemidophorus tigris; one anguid: Celestus costatus; one lacertid: Podarcis (Lacerta) sicula; and one iguanid: Crotaphytus wislizeni) were studied by transmission electron microscopy. Heterotopic synaptic bodies were found in some of the auditory hair cells of all of the above species, occurring frequently in the gekkonids but infrequently in other species. The groups of heterotopic synaptic bodies occurred mainly in the infranuclear cytoplasm between the hair cell nucleus and the hair cell plasma membrane. The groups of synaptic bodies that were close to the hair cell nucleus were usually associated with specialized arrays of rough and smooth endoplasmic reticulum. The numbers of heterotopic synaptic bodies were greatest in the gekkonid species and were especially large in Coleonyx variegatus, where an average of 36.8 synaptic bodies occur in one group. The functional significance of the presence of heterotopic synaptic bodies in the auditory hair cells of adults animals is not known.

Myositis ossificans in children: a review.

PubMed

Sferopoulos, N K; Kotakidou, R; Petropoulos, A S

2017-05-01

The formation of lamellar bone in the soft tissues, where bone normally does not exist, is called myositis ossificans. However, it would be more accurate to describe as myositis ossificans the involvement of skeletal muscles and as ectopic or heterotopic ossification the involvement of soft tissues in general. The lesion is subdivided in genetic and non-genetic or acquired types. Myositis or fibrodysplasia ossificans progressiva is a debilitating rare genetic disorder. Clinical suspicion of the disease in the newborn on the basis of malformed great toes may lead to early clinical diagnosis, confirmatory diagnostic genetic testing and avoidance of iatrogenic harmful procedures. Acquired lesions involve the neurogenic myositis ossificans and the non-neurogenic disorder. The latter is defined either as circumscribed myositis ossificans that is post-traumatic or as idiopathic/pseudomalignant myositis ossificans that is non-traumatic and may be a form fruste of fibrodysplasia ossificans progressiva. Ossification in fibrodysplasia ossificans progressiva is irreversible, unlike other forms of heterotopic ossification. In this retrospective study, a total of 22 children with myositis ossificans treated in a 20-year period were identified and classified. Two patients were diagnosed with myositis/fibrodysplasia ossificans progressiva, one with neurogenic myositis ossificans, one with idiopathic/pseudomalignant myositis ossificans and 18 patients with circumscribed myositis ossificans. The clinical features, imaging and histological findings as well as treatment modalities and complications of myositis ossificans in our patients are presented and discussed.

Heterotopic pregnancy in a cross border oocyte donation patient: the importance of cooperation between centers.

PubMed

Mancini, Fulvia; Clua, Elisabet; Martínez, Francisca; Battaglia, Cesare; Veiga, Anna; Barri, Pedro N

2011-06-01

To report a case of tubal heterotopic pregnancy after oocyte donation in a cross border patient. Case report. Private University Clinic, Spain, and Public University Hospital, Italy. A woman with a tubal heterotopic pregnancy after oocyte donation. Oocyte donation and ET (Spain), laparoscopic removal of the tubal heterotopic pregnancy (Italy). Diagnosis and treatment of the heterotopic pregnancy. Laparoscopic treatment of the heterotopic pregnancy resulting in a single ongoing intrauterine pregnancy. Cross border reproductive care is increasing in Europe. When patients go back to their respective countries of origin they may not inform their doctors about having undergone fertility treatments abroad. This can lead to a delayed diagnosis in case of complications arising after treatment or during pregnancy. It is of vital importance that clinicians are aware of this possibility to speed up the diagnosis and treatment of potentially fatal situations such as the one described in the present case report. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Twenty-Year Outcome After Right Ventricular Outflow Tract Repair Using Heterotopic Pulmonary Conduits in Infants and Children.

PubMed

Hoxha, Stiljan; Torre, Salvatore; Rungatscher, Alessio; Sandrini, Camilla; Rossetti, Lucia; Barozzi, Luca; Faggian, Giuseppe; Luciani, Giovanni Battista

2016-01-01

Durability of pulmonary conduits (PCs) used for reconstruction of the right ventricular outflow tract (RVOT) may be affected by a variety of factors. Among these, the technique used for PC implantation, whether in orthotopic or heterotopic position, strictly dependent upon the underlying anatomy, has been suggested to influence long-term outcome after RVOT repair. To determine the outcome of heterotopic implantation in infants and children treated at our institution, late results of heterotopic PC in non-Ross patients were analyzed and compared with data of orthotopic PC in age-matched pediatric Ross patients operated during the same time period. Between November 1991 and January 2015, 58 infants and children, 32 male and 26 female, with a median age of 9.4 years (range 1 day-18 years) underwent implantation of heterotopic PC (31 homografts [HG] and 27 xenografts [XG]) for reconstruction of RVOT. Median age in the XG group was significantly lower than in the HG group (0.9 vs. 13.4 years, P = 0.01), while male/female ratio was similar. Fifty (86%) patients had undergone one or more prior cardiac operations, while 32 (55%) required associated procedures during PC implantation. Comparison with data in 305 children and with a median age of 9.4 years, receiving orthotopic PC between 1990 and 2012 (Italian Pediatric Ross Registry), was undertaken. Descriptive, univariate, and Kaplan-Meier analysis defined outcome. There were three (5.2%) early and five (9.0%) late deaths, during a median follow-up of 7.6 years (range 2 months-23 years). Patients having XG had trend toward higher hospital mortality (2/27 vs. 1/31, P = 0.2), but similar late mortality (2/24 vs. 3/30, P = 0.3). Overall survival was 88 and 62%, while freedom from PC replacement was 49 and 21%, at 10 and 20 years, respectively. The latter proved significantly worse than freedom from orthotopic PC replacement, which was 94 ± 2 and 70 ± 9% at 10 and 20 years (P = 0.02). When stratified

Prenatal cranial ossification of the humpback whale (Megaptera novaeangliae).

PubMed

Hampe, Oliver; Franke, Helena; Hipsley, Christy A; Kardjilov, Nikolay; Müller, Johannes

2015-05-01

Being descendants of small terrestrial ungulate mammals, whales underwent enormous transformations during their evolutionary history, that is, extensive changes in anatomy, physiology, and behavior were evolved during secondary adaptations to life in water. However, still only little is known about whale ontogenetic development, which help to identify the timing and sequence of critical evolutionary events, such as modification of the cetacean ear. This is particularly true for baleen whales (Mysticeti), the group including the humpback whale Megaptera novaeangliae. We use high-resolution X-ray computed tomography to reinvestigate humpback whale fetuses from the Kükenthal collection at the Museum für Naturkunde, Berlin, thus, extending historic descriptions of their skeletogenesis and providing for the first time sequences of cranial ossification for this species. Principally, the ossification sequence of prenatal Megaptera follows a typical mammalian pattern with the anterior dermal bones being the first ossifying elements in the skull, starting with the dentary. In contrast to other mammals, the ectotympanic bone ossifies at an early stage. Alveolar structure can be observed in both the maxillae and dentaries in these early prenatal specimens but evidence for teeth is lacking. Although the possibility of obtaining new embryological material is unlikely due to conservation issues, our study shows that reexamination of existing specimens employing new technologies still holds promise for filling gaps in our knowledge of whale evolution and ontogeny. © 2015 Wiley Periodicals, Inc.

Mead acid (20:3n-9) and n-3 polyunsaturated fatty acids are not associated with risk of posterior longitudinal ligament ossification: results of a case-control study.

PubMed

Hamazaki, Kei; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Seki, Shoji; Hori, Takeshi; Hamazaki, Tomohito; Kimura, Tomoatsu

2015-05-01

Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnosis and Treatment of Heterotopic Ossification

DTIC Science & Technology

2014-10-01

junction molecule that regulates the “blood-nerve barrier”. These cells also now express the markers of extravasation , CD44 and CXCR4. These cells then...with these stem cells then entering the blood stream. During bone injury, they are recruited to the site of bone formation. Thus, there are many drugs ...bloodstream simultaneously with an increase in expression of factors involved in extravasation and the appearance of the osterix+ claudin 5

Diagnosis and Treatment of Heterotopic Ossification

DTIC Science & Technology

2015-10-01

low dose radiation that have some efficacy in preventing HO in patients at high risk, cannot be implemented in the majority of cases. Thus there are...and flowed through the vasculature to the site of bone formation where they extravasated into the newly forming bone [Lazard et al., 2015

Heterotopic Ossification Following Combat-Related Trauma

DTIC Science & Technology

2010-01-01

Nylen E, Brown TS, Rose MW, Stojadinovic A, Becker KL, McGuigan FX. Correlation of procalcitonin and cytokine expression with dehiscence of wartime...macular dystrophies . Arch Ophthalmol. 2003;121:967-72. 83. Schulmerich MV, Cole JH, Kreider JM, Esmonde-White F, Dooley KA, Goldstein SA, Morris MD

Patterns in the bony skull development of marsupials: high variation in onset of ossification and conserved regions of bone contact

PubMed Central

Spiekman, Stephan N. F.; Werneburg, Ingmar

2017-01-01

Development in marsupials is specialized towards an extremely short gestation and highly altricial newborns. As a result, marsupial neonates display morphological adaptations at birth related to functional constraints. However, little is known about the variability of marsupial skull development and its relation to morphological diversity. We studied bony skull development in five marsupial species. The relative timing of the onset of ossification was compared to literature data and the ossification sequence of the marsupial ancestor was reconstructed using squared-change parsimony. The high range of variation in the onset of ossification meant that no patterns could be observed that differentiate species. This finding challenges traditional studies concentrating on the onset of ossification as a marker for phylogeny or as a functional proxy. Our study presents observations on the developmental timing of cranial bone-to-bone contacts and their evolutionary implications. Although certain bone contacts display high levels of variation, connections of early and late development are quite conserved and informative. Bones that surround the oral cavity are generally the first to connect and the bones of the occipital region are among the last. We conclude that bone contact is preferable over onset of ossification for studying cranial bone development. PMID:28233826

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

Acute unilateral hip pain in fibrodysplasia ossificans progressiva (FOP).

PubMed

Kaplan, Frederick S; Al Mukaddam, Mona; Pignolo, Robert J

2018-04-01

Flare-ups of the hips are among the most feared and disabling complications of fibrodysplasia ossificans progressiva (FOP) and are poorly understood. In order to better understand the nature of hip flare-ups in FOP, we evaluated 25 consecutive individuals with classic FOP (14 males, 11 females; 3-56years old, median age, 17years old) who presented with acute unilateral hip pain. All 25 individuals were suspected of having a flare-up of the hip based on clinical history and a favorable response to a four day course of high-dose oral prednisone. Ten individuals (40%) experienced rebound symptoms of pain and/or stiffness within seven days after discontinuation of prednisone and all ten subsequently developed heterotopic ossification (HO) or decreased mobility of the affected hip. None of the 14 individuals who experienced sustained relief of symptoms following a course of oral prednisone experienced HO or decreased mobility. Incidental radiographic findings at the time of presentation were multifactoral and included osteochondromas of the proximal femur (18/25; 72%), degenerative arthritis (17/25; 68%), developmental hip dysplasia (15/25; 60%), previously existing heterotopic ossification (12/25; 48%), intra-articular synovial osteochondromatosis (8/25; 32%) or traumatic fractures through pre-existing heterotopic bone (1/25; 4%). Developmental joint pathology may confound clinical evaluation of hip pain in FOP. The most useful modality for suspecting an ossification-prone flare-up of the hip was lack of sustained response to a brief course of oral prednisone. Evaluation of soft tissue edema by ultrasound or magnetic resonance imaging showed promise in identifying ossification-prone flare-ups and warrants further analysis in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Restricted Mandibular Movement Attributed to Ossification of Mandibular Depressors and Medial Pterygoid Muscles in Patients With Fibrodysplasia Ossificans Progressiva: A Report of 3 Cases.

PubMed

Okuno, Tetsuko; Suzuki, Hitoshi; Inoue, Akio; Kusukawa, Jingo

2017-09-01

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic condition characterized by congenital malformation and progressive heterotopic ossification (HO) caused by a recurrent single nucleotide substitution at position 617 in the ACVR1 gene. As the condition progresses, HO leads to joint ankylosis, breathing difficulties, and mouth-opening restriction, and it can shorten the patient's lifespan. This report describes 3 cases of FOP confirmed by genetic testing in patients with restricted mouth opening. Each patient presented a different onset and degree of jaw movement restriction. The anatomic ossification site of the mandibular joint was examined in each patient using reconstructed computed tomographic (CT) images and 3-dimensional reconstructed CT (3D-CT) images. A 29-year-old woman complained of jaw movement restriction since 13 years of age. 3D-CT image of the mandibular joint showed an osseous bridge, formed by the mandibular depressors that open the mouth, between the hyoid bone and the mentum of the mandible. A 39-year-old man presented with jaw movement restriction that developed at 3 years of age after a mouth injury. 3D-CT image of the jaw showed ankylosis of the jaw from ossification of the mandibular depressors that was worse than in patient 1. CT images showed no HO findings of the masticatory muscles. To the authors' knowledge, these are the first 2 case descriptions of the anatomic site of ankylosis involving HO of the mandibular depressors in the jaw resulting from FOP. In contrast, a 62-year-old bedridden woman with an interincisal distance longer than 10 mm (onset, 39 years of age) had no HO of the mandibular depressors and slight HO of the medial pterygoid muscle on the right and left sides. These findings suggest that restricted mouth opening varies according to the presence or absence of HO of the mandibular depressors. Copyright © 2017. Published by Elsevier Inc.

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

PubMed Central

Dennis, S. Connor; Berkland, Cory J.; Bonewald, Lynda F.

2015-01-01

Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's “ideal” osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the “hard” or “bony” callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures and, thus, can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies which mimic the initial inflammatory or fibrocartilaginous ECM (i.e., “pro-” or “soft” callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (1) native ECM biomaterials and (2) developmental engineering, which will attempt to overcome the technical, business, and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native “raw” materials

Recurrent ectopic pregnancy in a woman suffering from infertility due to male factor presented with heterotopic pregnancy

PubMed Central

Chaudhari, Hemang D; Gandhi, Viplav S; Banker, Hiral; Suri, Amar

2012-01-01

Heterotopic pregnancy is the simultaneous occurrence of intrauterine and extrauterine pregnancies. A 27-year-old third gravida with history of two ectopic pregnancies, presented with cramping pain in pelvis radiating to left side and bleeding from vagina. Ultrasonographic diagnosis of heterotopic pregnancy was put forward. Unfortunately intrauterine component of heterotopic pregnancy resulted in blighted ovum and linear salpingostomy was done for left-sided tubal pregnancy. PMID:22605872

FGFR3 mutation causes abnormal membranous ossification in achondroplasia.

PubMed

Di Rocco, Federico; Biosse Duplan, Martin; Heuzé, Yann; Kaci, Nabil; Komla-Ebri, Davide; Munnich, Arnold; Mugniery, Emilie; Benoist-Lasselin, Catherine; Legeai-Mallet, Laurence

2014-06-01

FGFR3 gain-of-function mutations lead to both chondrodysplasias and craniosynostoses. Achondroplasia (ACH), the most frequent dwarfism, is due to an FGFR3-activating mutation which results in impaired endochondral ossification. The effects of the mutation on membranous ossification are unknown. Fgfr3(Y367C/+) mice mimicking ACH and craniofacial analysis of patients with ACH and FGFR3-related craniosynostoses provide an opportunity to address this issue. Studying the calvaria and skull base, we observed abnormal cartilage and premature fusion of the synchondroses leading to modifications of foramen magnum shape and size in Fgfr3(Y367C/+) mice, ACH and FGFR3-related craniosynostoses patients. Partial premature fusion of the coronal sutures and non-ossified gaps in frontal bones were also present in Fgfr3(Y367C/+) mice and ACH patients. Our data provide strong support that not only endochondral ossification but also membranous ossification is severely affected in ACH. Demonstration of the impact of FGFR3 mutations on craniofacial development should initiate novel pharmacological and surgical therapeutic approaches.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory

PubMed Central

Jones, Watson; Roberts, R. E.

1933-01-01

(1) Pathology of calcification and ossification.—The Leriche-Policard theories. Hyperæmia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. “Myositis ossificans.” (2) Radiological significance of density of bone shadows.—Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular. (3) Hyperæmic decalcification of bone.—Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperæmic dislocation of the atlas. Hyperæmic decalcification and nephrolithiasis. (4) Anæmic sclerosis of bone.—Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone—Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases. (5) Pathological calcification.—Calcification of supraspinatus tendon. Calcification of tumours—angioma, hæmatoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs. (6) Pathological ossification.—Ossification of tendons. Ossification of semilunar cartilages. PMID:19989304

High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva

PubMed Central

Cappato, Serena; Tonachini, Laura; Giacopelli, Francesca; Tirone, Mario; Galietta, Luis J. V.; Sormani, Martina; Giovenzana, Anna; Spinelli, Antonello E.; Canciani, Barbara; Brunelli, Silvia; Ravazzolo, Roberto

2016-01-01

ABSTRACT The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process. With the aim of finding a new therapeutic strategy for FOP, we developed a high-throughput screening (HTS) assay to identify inhibitors of ACVR1 gene expression among drugs already approved for the therapy of other diseases. The screening, based on an ACVR1 promoter assay, was followed by an in vitro and in vivo test to validate and characterize candidate molecules. Among compounds that modulate the ACVR1 promoter activity, we selected the one showing the highest inhibitory effect, dipyridamole, a drug that is currently used as a platelet anti-aggregant. The inhibitory effect was detectable on ACVR1 gene expression, on the whole Smad-dependent BMP signaling pathway, and on chondrogenic and osteogenic differentiation processes by in vitro cellular assays. Moreover, dipyridamole reduced the process of heterotopic bone formation in vivo. Our drug repositioning strategy has led to the identification of dipyridamole as a possible therapeutic tool for the treatment of FOP. Furthermore, our study has also defined a pipeline of assays that will be useful for the evaluation of other pharmacological inhibitors of heterotopic ossification. PMID:27125279

Ossification of thoracic ligamenta flava

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

Kudo, S.; Minoru, O.; Russell, W.J.

1983-07-01

Although ligamentum flavum ossification (LFO) often occurs in normal persons, there are no reports of its detection on lateral chest radiographs made during screening examinations. Review of 1,744 consecutive lateral chest radiographs identified LFO in 6.2% of males and 4.8% of females. LFO occurred mainly at the intervertebral segments from T9-T10 through T12-L1. Most prevalent was the hook-shaped LFO, protruding inferoirly from the inferior facets into the projections of the intervertabral foramina. Though LFO can cause severe neurologic symptoms, none of the affected persons in this study reported such symptoms. LFO was first visualized radiographically when the subjects were 20-40more » years old, and it may be a physiologic condition. The LFO in these cases existed independent of thoracic posterior longitudinal ligament ossification, diffuse idiopathic skeletal hyperostosis, and degenerative osteoarthritis.« less

Ossification of the posterior atlantoaxial membrane associated with atlas hypoplasia: A case report.

PubMed

Meng, Yichen; Zhou, Dongxiao; Gao, Rui; Ma, Jun; Wang, Ce; Zhou, Xuhui

2016-11-01

Hypoplasia with an intact posterior arch of the atlas and ossification of the posterior atlantoaxial membrane (PAAM) are individually rare. The patient presented with a 6-month history of progressive weakness and paresthesia of his lower extremities. Cervical myelopathy resulting from atlas hypoplasia and ossification of the posterior atlantoaxial membrane. Laminectomy of the atlas with duroplasty. Preoperative symptoms were alleviated. In most reported cases, either atlas hypoplasia or ossification of the PAAM is responsible for patients' myelopathy. The case illustrated here, to the best of our knowledge, is the first one with coexistent atlas hypoplasia and ossification of the PAAM. And laminectomy of the atlas with duroplasty provided satisfied outcome.

Developmental ossification sequences of the appendicular and axial skeleton in Kuttanad duck embryos (Anas platyrhynchos domesticus)

PubMed Central

Firdous, A.D.; Maya, S.; Massarat, K.; Baba, M.A.

2016-01-01

The processes of ossification sequences are poorly investigated for birds in general, even for domestic and experimental species and when it comes to the waterfowl it is almost negligible. Such sequences constitute a rich source of data on character evolution, and may even provide phylogenetic information. A pre-hatch developmental study on ossification sequences of axial and appendicular skeletal system in Kuttanad duck embryos was undertaken using 78 viable embryos. From day 3 to day 7 of incubation no ossification densities were seen both by alizarin red staining and computerized radiography. The first indication of ossification as small ossification centers in skull bones, clavicle, scapula, humerus, radius and ulna in forelimb and ilium, pubis femur and fibula in hind limb were observed on the 9th day of incubation. The ossification of the body of the ribs started at the 11th day of incubation towards the proximal extremity. On day 13th the ossification process of vertebrae was started from cervical end. The variation in appearance of the ossification centers in different bones at different stages of incubation period suggests relative importance of phylogeny to the sequences. PMID:26862514

Generation and Development of Paravertebral Ossification in Cervical Artificial Disk Replacement: A Detailed Analytic Report Using Coronal Reconstruction CT.

PubMed

Tian, Wei; Han, Xiao; Liu, Bo; He, Da; Lv, Yanwei; Yue, James

2017-04-01

A retrospective follow-up study and review of images in published papers. To determine whether true heterotopic ossification (HO) occurs in artificial disk replacement (ADR); to evaluate the incidence of paravertebral ossification (PO) and its influence on ADR. HO is typically defined as the abnormal formation of true bone within extraskeletal soft tissues. However, HO in ADR does not fit this definition precisely, as it originates from vertebral body, making it hard to distinguish radiologically from preexisting osteophytes. In this study, the term used for bone formation around ADR is PO. First, all images in the published papers were evaluated as to whether the presented PO in ADR fit the classic definition of HO or osteophytes. Second, we studied 37 consecutive patients who underwent ADR and follow-up for minimum 24 months. The preoperative and follow-up incidence of PO and its influence on range of motion were evaluated using x-ray and computed tomography. All 52 images of PO were found adjacent to the disk in 1 segment rather than entire cervical spine. Fifty (96.2%) of the POs were found to originate from the vertebral body rather than in the soft tissue. A total of 31 patients were included in the follow-up study. No significant difference was found in the incidence of PO between the follow-up and preoperation (61.29% vs. 48.39%, P>0.05). The range of motion of the ADR segment in patients with progressed PO (7.44±4.64 degrees) was significantly lower than that of patients with stable PO grade (12.13±4.42 degrees, P<0.01) at last follow-up. A proportion of HO might in fact be the natural development of preoperative osteophytes, which is unrelated to ADR; the remaining HO might be due to changes in biomechanical environment after surgery, which promotes the grade of osteophytes and affects the segment motion.

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2015-10-01

alpha 1 COL1A1 collagen, type I, alpha 1 COL2A1 collagen, type II, alpha 1 COL4A3 collagen, type IV, alpha 3 COMP cartilage oligomeric matrix protein...Symbol  Fold Regulation (15  days post injury)  Spp1  172.4535 Spp1  1105.6776 Col1a1   137.7958 Tac1  130.0625 ll1b  67.3332 Cxcl5  86.3414 ll10  49.9631... Col1a1   84.2834 Has1  45.5771 ll1b  74.488 Tac1  42.9908 Mmp9  69.8933 Cxcl1  25.259 ll10  40.5062 Mmp9  24.4814 Col11a1  38.3554 Alpl  23.9021 Cxcl1

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2015-10-01

enhancer binding protein (C/EBP), alpha COL10A1 collagen, type X, alpha 1 COL11A1 collagen, type XI, alpha 1 COL1A1 collagen, type I, alpha 1 COL2A1...172.4535 Spp1  1105.6776 Col1a1   137.7958 Tac1  130.0625 ll1b  67.3332 Cxcl5  86.3414 ll10  49.9631 Col1a1   84.2834 Has1  45.5771 ll1b  74.488 Tac1

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2014-10-01

Adipoq, BMP4, Col4a3, IGF2, MyoD1, Smad3); 3-20 fold lower elevation of expression of Col1a1 ; and 3-10 fold higher expression of MMP9 and Spp1...XI, alpha 1 COL1A1 collagen, type I, alpha 1 COL2A1 collagen, type II, alpha 1 COL4A3 collagen, type IV, alpha 3 COMP cartilage oligomeric matrix

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2015-10-01

collagen, type X, alpha 1 COL11A1 collagen, type XI, alpha 1 COL1A1 collagen, type I, alpha 1 COL2A1 collagen, type II, alpha 1 COL4A3 collagen, type IV...Symbol  Fold Regulation (8  days post injury)  Gene Symbol  Fold Regulation (15  days post injury)  Spp1  172.4535 Spp1  1105.6776 Col1a1   137.7958 Tac1...130.0625 ll1b  67.3332 Cxcl5  86.3414 ll10  49.9631 Col1a1   84.2834 Has1  45.5771 ll1b  74.488 Tac1  42.9908 Mmp9  69.8933 Cxcl1  25.259 ll10  40.5062

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2013-10-01

so that therapies for prevention or mitigation of HO can be optimally targeted. This study seeks to contribute to advancement in each of these key...SUPPLEMENTARY NOTES 14. ABSTRACT This study will recruit wounded warriors with severe extremity trauma, which places them at high risk for...define potential therapies for prevention or mitigation of HO. 15. SUBJECT TERMS Wound healing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Morphometric study of the neural ossification centers of the atlas and axis in the human fetus.

PubMed

Baumgart, Mariusz; Wiśniewski, Marcin; Grzonkowska, Magdalena; Małkowski, Bogdan; Badura, Mateusz; Szpinda, Michał

2016-12-01

The knowledge of the developing cervical spine and its individual vertebrae, including their neural processes may be useful in the diagnostics of congenital vertebral malformations. This study was performed to quantitatively examine the neural ossification centers of the atlas and axis with respect to their linear, planar and volumetric parameters. Using the methods of CT, digital-image analysis and statistics, the size of neural ossification centers in the atlas and axis in 55 spontaneously aborted human fetuses aged 17-30 weeks was studied. Without any male-female and right-left significant differences, the best fit growth dynamics for the neural ossification centers of the atlas and axis were, respectively, modelled by the following functions: for length: y = -13.461 + 6.140 × ln(age) ± 0.570 and y = -15.683 + 6.882 × ln(age) ± 0.503, for width: y = -4.006 + 1.930 × ln(age) ± 0.178 and y = -3.054 + 1.648 × ln(age) ± 0.178, for cross-sectional area: y = -7.362 + 0.780 × age ± 1.700 and y = -9.930 + 0.869 × age ± 1.911, and for volume: y = -6.417 + 0.836 × age ± 1.924 and y = -11.592 + 1.087 × age ± 2.509. The size of neural ossification centers of the atlas and axis shows neither sexual nor bilateral differences. The neural ossification centers of the atlas and axis grow logarithmically in both length and width and linearly in both cross-sectional area and volume. The numerical data relating to the size of neural ossification centers of the atlas and axis derived from the CT and digital-image analysis are considered specific-age reference values of potential relevance in both the ultrasound monitoring and the early detection of spinal abnormalities relating to the neural processes of the first two cervical vertebrae in the fetus.

Purse-string suture technique to enable laparoscopic management of the interstitial gestation of a heterotopic pregnancy.

PubMed

Aust, Thomas; O'Neill, Aoife; Cario, Gregory

2011-01-01

To describe the laparoscopic management of an interstitial gestation of a heterotopic pregnancy. Case report and technique description. Tertiary-level private practice. Woman with a 6-week gestation spontaneous heterotopic twin pregnancy: one twin intrauterine, one interstitial. A purse-string suture was applied to the proximal portion of the interstitial heterotopic pregnancy. To enable a cornual resection to be performed with minimal bleeding and without recourse to laparotomy. At 8 weeks gestation an ultrasound scan confirmed a viable singleton intrauterine pregnancy, but a scan at 12 weeks showed a missed miscarriage. The embedding of the suture into the uterine serosa prevents slipping of the ligature that could occur with a pretied loop. Copyright © 2011 American Society for Reproductive Medicine. All rights reserved.

Early Versus Late Weight-Bearing Protocols for Surgically Managed Posterior Wall Acetabular Fractures.

PubMed

Heare, Austin; Kramer, Nicholas; Salib, Christopher; Mauffrey, Cyril

2017-07-01

Despite overall improved outcomes with open reduction and internal fixation of acetabular fractures, posterior wall fractures show disproportionately poor results. The effect of weight bearing on outcomes of fracture management has been investigated in many lower extremity fractures, but evidence-based recommendations in posterior wall acetabular fractures are lacking. The authors systematically reviewed the current literature to determine if a difference in outcome exists between early and late postoperative weight-bearing protocols for surgically managed posterior wall acetabular fractures. PubMed and MEDLINE were searched for posterior wall acetabular fracture studies that included weight-bearing protocols and Merle d'Aubigné functional scores. Twelve studies were identified. Each study was classified as either early or late weight bearing. Early weight bearing was defined as full, unrestricted weight bearing at or before 12 weeks postoperatively. Late weight bearing was defined as restricted weight bearing for greater than 12 weeks postoperatively. The 2 categories were then compared by functional score using a 2-tailed t test and by complication rate using chi-square analysis. Six studies (152 fractures) were placed in the early weight-bearing category. Six studies (302 fractures) were placed in the late weight-bearing category. No significant difference in Merle d'Aubigné functional scores was found between the 2 groups. No difference was found regarding heterotopic ossification, avascular necrosis, superficial infections, total infections, or osteoarthritis. This systematic review found no difference in functional outcome scores or complication rates between early and late weight-bearing protocols for surgically treated posterior wall fractures. [Orthopedics. 2017: 40(4):e652-e657.]. Copyright 2017, SLACK Incorporated.

Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10. 00 Gy vs 20. 00 Gy schedules

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

Anthony, P.; Keys, H.; Evarts, C.M.

1987-03-01

Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As ofmore » February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. It historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients.« less

Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig.

PubMed

De Wolf, Julien; Brieu, Mathias; Zawadzki, Christophe; Ung, Alexandre; Kipnis, Eric; Jashari, Ramadan; Hubert, Thomas; Fayoux, Pierre; Mariette, Christophe; Copin, Marie-Christine; Wurtz, Alain

2017-08-01

It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups. An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58. Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Heterotopic gray matter. Neuroradiological aspects and clinical correlations.

PubMed

Canapicchi, R; Padolecchia, R; Puglioli, M; Collavoli, P; Marcella, F; Valleriani, A M

1990-01-01

Anomalies of cell migration manifest themselves in many ways with various clinical and morphological aspects. Among these, heterotopic gray matter, especially when isolated, is characterized by slighter symptoms and later onset. In this paper eight cases of gray matter heterotopia are presented which have been studied over a two-year period. Magnetic Resonance imaging is emphasised for a correct diagnosis.

Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.

PubMed

Braddock, Rattana; Simán, C Martin; Hamilton, Katherine; Garland, Hugh O; Sibley, Colin P

2002-05-01

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.

Ossification score is a better indicator of maturity related changes in eating quality than animal age.

PubMed

Bonny, S P F; Pethick, D W; Legrand, I; Wierzbicki, J; Allen, P; Farmer, L J; Polkinghorne, R J; Hocquette, J-F; Gardner, G E

2016-04-01

Ossification score and animal age are both used as proxies for maturity-related collagen crosslinking and consequently decreases in beef tenderness. Ossification score is strongly influenced by the hormonal status of the animal and may therefore better reflect physiological maturity and consequently eating quality. As part of a broader cross-European study, local consumers scored 18 different muscle types cooked in three ways from 482 carcasses with ages ranging from 590 to 6135 days and ossification scores ranging from 110 to 590. The data were studied across three different maturity ranges; the complete range of maturities, a lesser range and a more mature range. The lesser maturity group consisted of carcasses having either an ossification score of 200 or less or an age of 987 days or less with the remainder in the greater maturity group. The three different maturity ranges were analysed separately with a linear mixed effects model. Across all the data, and for the greater maturity group, animal age had a greater magnitude of effect on eating quality than ossification score. This is likely due to a loss of sensitivity in mature carcasses where ossification approached and even reached the maximum value. In contrast, age had no relationship with eating quality for the lesser maturity group, leaving ossification score as the more appropriate measure. Therefore ossification score is more appropriate for most commercial beef carcasses, however it is inadequate for carcasses with greater maturity such as cull cows. Both measures may therefore be required in models to predict eating quality over populations with a wide range in maturity.

Time-dependent expression of ICAM-1 & VCAM-1 on coronaries of the heterotopically transplanted mouse heart.

PubMed Central

Lee, J. R.; Huh, J. H.; Seo, J. W.; Suk, C. J.; Jeong, H. M.; Kim, E. K.

1999-01-01

To investigate the pathogenesis of accelerated graft atherosclerosis after cardiac transplantation, a genetically well-defined and reproducible animal model is required. We performed heterotopic intraabdominal heart transplantation between the two inbred strains of mice. Forty hearts from B10.A mice were transplanted into B10.BR mice. Recipients were sacrificed at 1, 3, 5, 7, 14, 28, and 42 days after implantation. The specimens from both donor and recipient were examined with fluorescent immunohistochemistry and the serial histopathologic changes were evaluated. In the donor hearts, ICAM-1 and VCAM-1 expressions were minimal at day 1 and they gradually increased, reaching their peaks on day 5 or 7 and remained unchanged by day 42. However, there were very little expressions in the recipients' hearts. Mean percent areas of intima in the donor coronaries revealed progressive increase by day 42. However, those in the recipients occupied consistently less than 5% of the lumen. In conclusion, we demonstrated that a heterotopic murine heart transplantation model was a useful tool to produce transplantation coronary artery disease and that adhesion molecules on the cardiac allografts were activated very early and remained elevated at all time-points, nonetheless the arterial lesion was detected after day 28 and its progression was accelerated thereafter. PMID:10402165

Cystic dystrophy of the gastric and duodenal wall developing in heterotopic pancreas: an unrecognised entity.

PubMed Central

Fléjou, J F; Potet, F; Molas, G; Bernades, P; Amouyal, P; Fékété, F

1993-01-01

Ten patients in whom cystic dystrophy developed in a heterotopic pancreas of the duodenal (nine patients) or gastric (one patient) wall are reported. All were young or middle aged white men, only two of whom were alcoholic. The symptoms were caused by intestinal or biliary stenosis, or both, secondary to the inflammation and fibrosis. Only endosonography provided strong evidence for the diagnosis in three patients. All patients underwent surgery: a pancreaticoduodenectomy was performed in eight patients. The surgical specimen showed cystic lesions of the gut wall, occurring in inflammatory and fibrous heterotopic pancreatic tissue. The pancreas proper was normal in all patients. It is suggested that cystic dystrophy is an uncommon and serious complication of heterotopic pancreas. Similar cases associated with chronic pancreatitis of the pancreas have been observed and it is suggested that this process could be responsible for some of the chronic pancreatitis encountered in young, non-alcoholic patients. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8097180

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs

PubMed Central

Peck, Sun H.; O'Donnell, Philip J.M.; Kang, Jennifer L.; Malhotra, Neil R.; Dodge, George R.; Pacifici, Maurizio; Shore, Eileen M.; Haskins, Mark E.; Smith, Lachlan J.

2015-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein

Ossification of transverse ligament of atlas causing cervical myelopathy: a case report and review of the literature.

PubMed

Sasaji, Tatsuro; Kawahara, Chikashi; Matsumoto, Fujio

2011-01-01

A case of ossification of transverse ligament of atlas (TLA) is reported. A 76-year-old female suffered from a transverse type myelopathy was successfully treated by posterior decompression. Dynamic lateral plain radiographs showed irreducible atlantoaxial subluxation (AAS). A computed tomogram revealed ossified mass compatible to ossification of TLA. Coalition of the atlantooccipital joints and osteoarthritis of the atlantoaxial joints with degenerated dens was also revealed. Magnetic resonance imaging showed compressed spinal cord at C1 level by the ossification of TLA and AAS. We suggest a mechanism of ossification of TLA as follows: hypertrophied dens and stress to the atlantoaxial joints caused by coalition of atlantooccipital joints could make forward shift of atlas leading to irreducible AAS, and continuous tension given to TLA from irreducible AAS would result in hypertrophied and ossification of TLA.

Does colonization of Helicobacter pylori in the heterotopic gastric mucosa play a role in bleeding of Meckel's diverticulum?

PubMed

Ergün, Orkan; Celik, Ahmet; Akarca, Ulus S; Sen, Teoman; Alkanat, Murat; Erdener, Ata

2002-11-01

Helicobacter pylori is a microorganism known to colonize in gastric type of mucosa and is associated with gastritis and peptic ulceration. The aim of the study was to determine whether colonization of H pylori in heterotopic gastric mucosa plays a role in bleeding of Meckel's diverticulum. Histopathologic slides of patients who had undergone resection of Meckel's diverticulum in recent 5 years were reexamined for the presence of H pylori in heterotopic gastric mucosa. Polimerase chain reaction (PCR) test was used to trace the genetic material of urease gene and 16s rDNA amplifications for H pylori. Thirteen of the 30 histopathologic slides of Meckel's diverticula had heterotopic gastric mucosa. Ten of the 13 patients presented with acute bleeding of the diverticula, whereas 3 of them were asymptomatic. None of the 13 gastric mucosa bearing diverticula were colonized with H pylori. PCR was unable to show any trace of genetic material for H pylori. Although the role of H pylori is well established in the gastric mucosal ulceration, its presence is not essentially required to induce "heterotopic gastritis" that may result in bleeding of the Meckel's diverticulum. . Copyright 2002, Elsevier Science (USA). All rights reserved.

[Clinical and ossification outcome of custom-made hydroxyapatite prothese for large skull defect].

PubMed

Hardy, H; Tollard, E; Derrey, S; Delcampe, P; Péron, J-M; Fréger, P; Proust, F

2012-02-01

Cranioplasty is an everyday concern in neurosurgery, especially in decompressive craniectomy cases. Our surgical team uses custom-made hydroxyapatite implants for large and/or complex defects. Eight patients had a custom-made prosthesis. Each of them has been reviewed by an independent observer. Each patient described his feeling of satisfaction, using a questionnaire, graduated from "A" (really satisfied) to "D" (unsatisfied). Each of them also underwent a CT-scan (helicoidal acquisition, 0.6mm thick for multiplanar reconstruction) to evaluate qualitatively the ossification graduated from "0" (no ossification) to "5" (continuous ossification). Maximal under-prosthetic bone thickness, intra-prosthetic calcic density were also reported. Supervision delay was 43.7 months [6-99 months], average defect surface was 85.5 cm(2) [27.6-137.6 cm(2)], the craniectomy etiologies were intracranial hypertension (seven patients) and calvarial invasion (one patient). Implant tolerance was reparted in "A" score (50%) and "B" score (50%). Concerning ossification, six patients (75%) had a score of "2" or less and two patients had a score of "3" or "4". Hydroxyapatite custom-made implants for cranioplasty appear to be ideal for good aesthetic and tolerance results, but their ossification is hardly analyzed due to the prosthesis density higher than the bone's density. This is why we recommend them for children and in cases of complex defects such as pterion location. Copyright © 2011. Published by Elsevier Masson SAS.

Revision Proximal Interphalangeal Arthroplasty: An Outcome Analysis of 75 Consecutive Cases.

PubMed

Wagner, Eric R; Luo, T David; Houdek, Matthew T; Kor, Daryl J; Moran, Steven L; Rizzo, Marco

2015-10-01

To examine the outcomes and complications associated with revision proximal interphalangeal (PIP) joint arthroplasty. An analysis of 75 consecutive revision PIP joint arthroplasties in 49 patients, performed between 1998 to 2012, was performed. The mean age at the time of surgery was 58 years. Thirty-two patients had a history of prior PIP joint trauma, and 18 patients had rheumatoid arthritis. There were 12 constrained (silicone) implants and 63 nonconstrained implants (34 pyrocarbon and 29 metal-plastic). Over the 14-year period, 19 (25%) fingers underwent a second revision surgery. Second revision surgeries were performed for infection, instability, flexion contracture, and heterotopic ossification. The 2-, 5-, and 10-year survival rates were 80%, 70%, and 70%, respectively, for patients requiring a second revision for PIP joint arthroplasty. Worse outcomes were seen with postoperative dislocations, pyrocarbon implants, and when bone grafting was required. Two operations were complicated by intraoperative fractures, but neither required stabilization. Sixteen patients undergoing revision surgery experienced a postoperative complication, including 2 infections, 1 postoperative fracture, 3 cases of heterotopic ossification, and 10 PIP joint dislocations. The volar approach and the use of a pyrocarbon implant was associated with increased rates of heterotopic ossification, whereas preoperative instability increased the rates of PIP joint dislocation following revision. At a mean of 5.3 years (range, 2-10 years) follow-up, 98% of patients had good pain relief but decreased PIP joint total arc of motion. Proximal interphalangeal joint arthroplasty in the revision setting represents a challenge for surgeons. Revision arthroplasty was associated with a 70% 5-year survival but with a high incidence of complications. Instability was associated with worse outcomes. In this series, silicone and metal-polyethylene implants had lower rates of implant failure and

Proteomic Analysis of Trauma-Induced Heterotopic Ossification Formation

DTIC Science & Technology

2014-10-01

journal name, book title, editors(s), publisher, volume number, page number(s), date, DOI, PMID, and/or ISBN. (1) Lay Press: a. Arthur Nead...Blast Injured. September 24, 2014. http://www.newswise.com/articles/ . c. Amy Andersen . Possible New Treatment For Soft Tissue Bone Formation In

Quantitative Analyses of Pediatric Cervical Spine Ossification Patterns Using Computed Tomography

PubMed Central

Yoganandan, Narayan; Pintar, Frank A.; Lew, Sean M.; Rao, Raj D.; Rangarajan, Nagarajan

2011-01-01

The objective of the present study was to quantify ossification processes of the human pediatric cervical spine. Computed tomography images were obtained from a high resolution scanner according to clinical protocols. Bone window images were used to identify the presence of the primary synchondroses of the atlas, axis, and C3 vertebrae in 101 children. Principles of logistic regression were used to determine probability distributions as a function of subject age for each synchondrosis for each vertebra. The mean and 95% upper and 95% lower confidence intervals are given for each dataset delineating probability curves. Posterior ossifications preceded bilateral anterior closures of the synchondroses in all vertebrae. However, ossifications occurred at different ages. Logistic regression results for closures of different synchondrosis indicated p-values of <0.001 for the atlas, ranging from 0.002 to <0.001 for the axis, and 0.021 to 0.005 for the C3 vertebra. Fifty percent probability of three, two, and one synchondroses occurred at 2.53, 6.97, and 7.57 years of age for the atlas; 3.59, 4.74, and 5.7 years of age for the axis; and 1.28, 2.22, and 3.17 years of age for the third cervical vertebrae, respectively. Ossifications occurring at different ages indicate non-uniform maturations of bone growth/strength. They provide an anatomical rationale to reexamine dummies, scaling processes, and injury metrics for improved understanding of pediatric neck injuries PMID:22105393

Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs

NASA Technical Reports Server (NTRS)

Dziedzic-Goclawska, A.; Toverud, S. U.; Kaminski, A.; Boass, A.; Yamauchi, M.

1992-01-01

The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and -D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation.

Glenoid labrum ossification and mechanical restriction of joint motion: extraosseous manifestations of melorheostosis.

PubMed

Subhas, N; Sundaram, M; Bauer, T W; Seitz, W H; Recht, M P

2008-02-01

We report a case of a 47-year-old man who presented with progressive loss of motion and pain in the right shoulder. Radiographs of the shoulder demonstrated dense ossification in the glenoid and humeral head with extension into the periarticular soft tissues. CT and MRI scans confirmed the radiographic findings and also revealed ossification of the glenoid labrum. A radiographic diagnosis of melorheostosis, an uncommon benign sclerosing bone dysplasia, was made. Because of the patient's severe symptomatology, he underwent total shoulder arthroplasty. Histological analysis of the resected masses was consistent with melorheostosis with a few areas covered by a cartilage cap. This case illustrates several uncommon but important features of melorheostosis, including mechanical obstruction of joint motion requiring joint replacement, ossification of the glenoid labrum, and cartilage-covering portions of the intra-articular masses, not to be confused with cartilage-producing tumors.

Fungal osteomyelitis with vertebral re-ossification.

PubMed

O Guinn, Devon J; Serletis, Demitre; Kazemi, Noojan

2016-01-01

We present a rare case of thoracic vertebral osteomyelitis secondary to pulmonary Blastomyces dermatitides. A 27-year-old male presented with three months of chest pains and non-productive cough. Examination revealed diminished breath sounds on the right. CT/MR imaging confirmed a right-sided pre-/paravertebral soft tissue mass and destructive lytic lesions from T2 to T6. CT-guided needle biopsy confirmed granulomatous pulmonary Blastomycosis. Conservative management with antifungal therapy was initiated. Neurosurgical review confirmed no clinical or profound radiographic instability, and the patient was stabilized with TLSO bracing. Serial imaging 3 months later revealed near-resolution of the thoracic soft tissue mass, with vertebral re-ossification from T2 to T6. Fungal osteomyelitis presents a rare entity in the spectrum of spinal infections. In such cases, lytic spinal lesions are classically seen in association with a large paraspinous mass. Fungal infections of the spinal column may be treated conservatively, with surgical intervention reserved for progressive cases manifesting with neurological compromise and/or spinal column instability. Here, we found unexpected evidence for vertebral re-ossification across the affected thoracic levels (T2-6) in response to IV antibiotic therapy and conservative bracing, nearly 3 months later. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fungal osteomyelitis with vertebral re-ossification

PubMed Central

O′Guinn, Devon J.; Serletis, Demitre; Kazemi, Noojan

2015-01-01

Introduction We present a rare case of thoracic vertebral osteomyelitis secondary to pulmonary Blastomyces dermatitides. Presentation of case A 27-year-old male presented with three months of chest pains and non-productive cough. Examination revealed diminished breath sounds on the right. CT/MR imaging confirmed a right-sided pre-/paravertebral soft tissue mass and destructive lytic lesions from T2 to T6. CT-guided needle biopsy confirmed granulomatous pulmonary Blastomycosis. Conservative management with antifungal therapy was initiated. Neurosurgical review confirmed no clinical or profound radiographic instability, and the patient was stabilized with TLSO bracing. Serial imaging 3 months later revealed near-resolution of the thoracic soft tissue mass, with vertebral re-ossification from T2 to T6. Discussion Fungal osteomyelitis presents a rare entity in the spectrum of spinal infections. In such cases, lytic spinal lesions are classically seen in association with a large paraspinous mass. Fungal infections of the spinal column may be treated conservatively, with surgical intervention reserved for progressive cases manifesting with neurological compromise and/or spinal column instability. Here, we found unexpected evidence for vertebral re-ossification across the affected thoracic levels (T2-6) in response to IV antibiotic therapy and conservative bracing, nearly 3 months later. PMID:26692163

Endochondral ossification is required for haematopoietic stem-cell niche formation.

PubMed

Chan, Charles K F; Chen, Ching-Cheng; Luppen, Cynthia A; Kim, Jae-Beom; DeBoer, Anthony T; Wei, Kevin; Helms, Jill A; Kuo, Calvin J; Kraft, Daniel L; Weissman, Irving L

2009-01-22

Little is known about the formation of niches, local micro-environments required for stem-cell maintenance. Here we develop an in vivo assay for adult haematopoietic stem-cell (HSC) niche formation. With this assay, we identified a population of progenitor cells with surface markers CD45(-)Tie2(-)alpha(V)(+)CD105(+)Thy1.1(-) (CD105(+)Thy1(-)) that, when sorted from 15.5 days post-coitum fetal bones and transplanted under the adult mouse kidney capsule, could recruit host-derived blood vessels, produce donor-derived ectopic bones through a cartilage intermediate and generate a marrow cavity populated by host-derived long-term reconstituting HSC (LT-HSC). In contrast, CD45(-)Tie2(-)alpha(V)(+)CD105(+)Thy1(+) (CD105(+)Thy1(+)) fetal bone progenitors form bone that does not contain a marrow cavity. Suppressing expression of factors involved in endochondral ossification, such as osterix and vascular endothelial growth factor (VEGF), inhibited niche generation. CD105(+)Thy1(-) progenitor populations derived from regions of the fetal mandible or calvaria that do not undergo endochondral ossification formed only bone without marrow in our assay. Collectively, our data implicate endochondral ossification, bone formation that proceeds through a cartilage intermediate, as a requirement for adult HSC niche formation.

Circumscribed myositis ossificans of the masseter muscle: report of a case

PubMed Central

PIOMBINO, P.; ORABONA, G. DELL’AVERSANA; ABBATE, V.; FINI, G.; LIBERATORE, G.M.; MICI, E.; BELLI, E.

2013-01-01

Summary Myositis Ossificans (MO) is an unusual pathological entity still largely unknown, characterized by dystrophic calcification leading to heterotopic ossification of intramuscular connective tissue. The masticatory muscles are exceptionally involved. Four distinct types of myositis ossificans have been described: MO Progressiva, which is a genetic disorder involving several muscular groups; MO Circumscripta, limited to a single muscle and generally due to calcification of an intramuscular haematoma following severe trauma and progressive ossification; MO Pseudo-malignant limited to soft tissue and not associated to any trauma; MO associated to paraplegia. A case of circumscribed myositis ossificans of the masseter muscle in a 62 years-old woma is reportedn. PMID:24629814

Medium-term outcome in patients treated with total hip arthroplasty using a modular femoral stem.

PubMed

Dagnino, Augusto; Grappiolo, Guido; Benazzo, Franco M; Learmonth, Ian D; Spotorno, Lorenzo; Portinaro, Nicola

2012-01-01

The clinical, radiographic and quality of life results of total hip arthroplasty using the MODULUS cementless modular femoral stem were reviewed. 48 patients who had a total hip arthroplasty using the MODULUS femoral stem were identified. Six had bilateral procedures, resulting in 60 hips with complete clinical and radiographic data. Mean age at implantation was 50 years (range 33 to 82). Mean follow-up was 59 months (range 50 months to 73). There were two early post-operative dislocations (within 2 days). One patient required further surgery to remove heterotopic bone. Mean Harris Hip Score increased from 37 points preoperatively (range, 7 to 66) to 89 points at final review (range, 65 to 100 points). Radiographic evaluation revealed that all implants were stable without evidence of osteolysis but three patients (5%) exhibited heterotopic ossification. Quality of life was evaluated with the SF36. The physical component increased from 29.2 points (range, 18.5 to 46.0) to 51.7 points (range 42.9 to 60.6) and the mental component from 375 points (range, 19.5 to 50.0) to 50 points (range 32,8 to 62.0).

Heterotopic gastric mucosa in gallbladder—A rare differential diagnosis to gallbladder masses

PubMed Central

Beeskow, Anne Bettina; Meyer, Hans-Jonas; Schierle, Katrin; Surov, Alexey

2018-01-01

Abstract Background: Heterotopic gastric tissue can be found in the entire gastrointestinal tract. It is usually located in the upper intestine. Rarely, it can be found in the gallbladder. This study describes several clinically, imaging features as well as histopathology findings of heterotopic gastric tissue in gallbladder (HGM). Methods: The radiologic database of 1 tertiary university hospital was retrospectively screened for HGM. Additionally, a systemic review of the Medline database was conducted to identify previously published cases reports. In all cases clinical, imaging as well as histopathology features were retrieved from the papers. Results: In our databases, 1 patient with HGM was identified. Additionally, the systemic review yielded 32 suitable papers with 34 patients. Clinically, most of the patients suffered from abdominal discomfort. Most of the lesions were located in the lower gallbladder, especially (n = 14, 40%) in the gallbladder neck. On sonography, in 20.7% a broad-based mass was described. In 10.3% a sessile polyp was identified. In 5 cases, the mass was characterized as hyperechoic (55.5%), as isoechoic in 3 (33.3%) cases, and hypoechoic in 1 (11.1%). On computed tomography (CT), the lesions were most frequently hyperdense and all of them showed a slightly enhancement after application of contrast medium. On histopathology, most cases revealed heterotopic gastric mucosa of body-fundic type (60%) with chief and parietal cells, followed by pyloric type glands (20%). Every patient was treated with cholecystectomy and all had an uneventful recovery. Conclusion: HGM is a rare disorder with several differential diagnoses. Typically features were described to identify HGM in clinical routine and rule out malignant diseases like gallbladder carcinoma. PMID:29517663

Osteogenic differentiation of periosteum-derived stromal cells in blast-associated traumatic loading

NASA Astrophysics Data System (ADS)

Sory, David R.; Amin, Harsh D.; Rankin, Sara M.; Proud, William G.

2017-06-01

One of the most recurrent medical complications resulting from blast trauma includes blast-induced heterotopic ossification. Heterotopic ossification refers to the pathologic formation of extraskeletal bone in non-osseous tissue. Although a number of studies have established the interaction between mechanics and biology in bone formation following shock trauma, the exact nature of the mechanical stimuli associated to blast-loading and their influence on the activation of osteogenic differentiation of cells remain unanswered. Here we present the design and calibration of a loading platform compatible with living cells to examine the effects of mechanical stress pulses of blast-associated varying strain rates on the activation of osteogenic differentiation of periosteum (PO) cells. Multiaxial compression loadings of PO cells are performed at different magnitudes of stress and ranges of strain rate. A proof of concept is presented so as to establish a new window to address fundamental questions regarding blast injuries at the cellular level. This work was conducted under the auspices of the Royal British Legion Centre for Blast Injury Studies at Imperial College London. The authors would like to acknowledge the financial support of the Royal British Legion.

Early Identification of Molecular Predictors of Heterotopic Ossification Following Extremity Blast Injury with a Biomarker Assay

DTIC Science & Technology

2015-10-01

extremity war-time wounds; specifically, its incidence is reported as high as 57% in patients that sustain a poly -trauma blast injury [1]. Complications...related to HO in residual limbs following blast amputation include pain , overlying skin and muscle breakdown, poor fitting and functioning of prosthetic

Early Identification of Molecular Predictors of Heterotopic Ossification Following Extremity Blast Injury with a Biomarker Assay

DTIC Science & Technology

2016-10-01

incidence is reported between 57-63% in patients that sustain a poly -trauma blast injury [1,2]. Complications related to HO in residual limbs...following blast amputation include pain , overlying skin and muscle breakdown, poor fitting and functioning of prosthetic limbs, reoperation for amputation

Early Identification of Molecular Predictors of Heterotopic Ossification Following Extremity Blast Injury with a Biomarker Assay

DTIC Science & Technology

2018-03-01

Charleston SC, 29425 REPORT DATE: March 2018 TYPE OF REPORT : Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick...this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so...

Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.

PubMed

Kaplan, Frederick S; Andolina, Jeffrey R; Adamson, Peter C; Teachey, David T; Finklestein, Jerry Z; Ebb, David H; Whitehead, Benjamin; Jacobs, Benjamin; Siegel, David M; Keen, Richard; Hsiao, Edward; Pignolo, Robert J

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. One such drug is imatinib mesylate, a tyrosine kinase inhibitor originally developed for use in patients with chronic myeloid leukemia (CML). Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-α, PDGFRα, c-KIT, and multiple MAP kinases. Based on compelling biologic rationale, strong preclinical data, and a favorable safety profile, imatinib has been prescribed on an off-label basis in a non-trial setting in seven children with continuous FOP flare-ups, predominantly in the axial regions, and which were not responsive to standard-of-care regimens. Anecdotal reports in these seven isolated cases document that the medication was well-tolerated with a ubiquitous reported decrease in the intensity of flare-ups in the six children who took the medication. These early clinical observations support the implementation of clinical trials in children with uncontrolled FOP flare-ups to determine if imatinib may ameliorate symptoms or alter the natural history of this debilitating and life-threatening disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Identity Formation and Affective Spaces in Conflict-Ridden Societies: Inventing Heterotopic Possibilities

ERIC Educational Resources Information Center

Zembylas, Michalinos; Ferreira, Ana

2009-01-01

In this article, we present vignettes from two projects--one in Cyprus and the other in South Africa--to show how some classrooms enact "heterotopic" affective spaces that oppose normal/ized identities, that is, identities grounded in polarized trauma narratives. The notion of heterotopia is a spatial concept developed by Foucault to…

Cyclin-dependent kinase inhibitor p21 does not impact embryonic endochondral ossification in mice

PubMed Central

CHINZEI, NOBUAKI; HAYASHI, SHINYA; HASHIMOTO, SHINGO; KANZAKI, NORIYUKI; IWASA, KENJIRO; SAKATA, SHUHEI; KIHARA, SHINSUKE; FUJISHIRO, TAKAAKI; KURODA, RYOSUKE; KUROSAKA, MASAHIRO

2015-01-01

Endochondral ossification at the growth plate is regulated by a number of factors and hormones. The cyclin-dependent kinase inhibitor p21 has been identified as a cell cycle regulator and its expression has been reported to be essential for endochondral ossification in vitro. However, to the best of our knowledge, the function of p21 in endochondral ossification has not been evaluated in vivo. Therefore, the aim of this study was to investigate the function of p21 in embryonic endochondral ossification in vivo. Wild-type (WT) and p21 knockout (KO) pregnant heterozygous mice were sacrificed on embryonic days E13.5, E15.5 and E18.5. Sagittal histological sections of the forearms of the embryos were collected and stained with Safranin O and 5-bromo-2′-deoxyuridine (BrdU). Additionally, the expression levels of cyclin D1, type II collagen, type X collagen, Sox9, and p16 were examined using immunohistochemistry, and the expression levels of p27 were examined using immunofluorescence. Safranin O staining revealed no structural change between the cartilage tissues of the WT and p21KO mice at any time point. Type II collagen was expressed ubiquitously, while type X collagen was only expressed in the hypertrophic zone of the cartilage tissues. No differences in the levels of Sox9 expression were observed between the two groups at any time point. The levels of cyclin D1 expression and BrdU uptake were higher in the E13.5 cartilage tissue compared with those observed in the embryonic cartilage tissue at subsequent time points. Expression of p16 and p27 was ubiquitous throughout the tissue sections. These results indicate that p21 may not be essential for embryonic endochondral ossification in articular cartilage of mice and that other signaling networks may compensate for p21 deletion. PMID:25376471

Pediatric Diaphyseal Femur Fractures: Submuscular Plating Compared With Intramedullary Nailing.

PubMed

Sutphen, Sean A; Mendoza, Juan D; Mundy, Andrew C; Yang, Jingzhen G; Beebe, Allan C; Samora, Walter P; Klingele, Kevin E

2016-11-01

This study compared the radiographic and clinical outcomes of pediatric diaphyseal femur fractures treated by submuscular plating, flexible retrograde intramedullary nailing, or rigid antegrade intramedullary nailing with a trochanteric entry point in skeletally immature patients who were 8 years and older. A retrospective review was conducted of skeletally immature patients 8 years and older who were treated for femur fracture with submuscular plating, flexible intramedullary nailing, or rigid intramedullary nailing from 2001 to 2014 with a minimum 12-week follow-up. Treatment outcomes were compared for statistical significance, including time to union, malunion, nonunion, heterotopic ossification, avascular necrosis, time to full weight bearing, limb length discrepancy, residual limp, painful hardware, and infection. The study identified 198 femur fractures in 196 patients (mean age, 11.9 years). Each femur fracture was treated with submuscular plating (35), flexible intramedullary nailing (61), or rigid intramedullary nailing (102). Mean follow-up across the cohort was 48 weeks, ranging from 12 to 225 weeks. Flexible nailing was associated with an increased incidence of malunion (P<.0001) and hardware irritation (P=.0204) and longer time to full weight bearing (P=.0018). Rigid nailing was associated with an increased incidence of limp at 12-week followup (P=.0412). Additionally, 23.5% of patients who were treated with rigid nailing had heterotopic ossification. Of all surgical methods, submuscular plating allowed for the most rapid return to full weight bearing (mean, 7 weeks) and offered the fastest healing rate (mean, 6 weeks). Submuscular plating resulted in faster times to union and full weight bearing, with minimal complication rates. Rigid intramedullary nailing with trochanteric entry resulted in a lower incidence of malunion and hardware-related complications; however, these patients had an increased incidence of heterotopic ossification and residual

Pre-clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique.

PubMed

Abicht, Jan-Michael; Mayr, Tanja; Reichart, Bruno; Buchholz, Stefan; Werner, Fabian; Lutzmann, Isabelle; Schmoeckel, Michael; Bauer, Andreas; Thormann, Michael; Langenmayer, Martin; Herbach, Nadja; Pohla, Heike; Herzog, Rudolf; McGregor, Christopher G A; Ayares, David; Wolf, Eckhard; Klymiuk, Nikolai; Baehr, Andrea; Kind, Alexander; Hagl, Christian; Ganswindt, Ute; Belka, Claus; Guethoff, Sonja; Brenner, Paolo

2015-01-01

As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient's native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/± thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed pre

An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva

PubMed Central

Chakkalakal, Salin A.; Zhang, Deyu; Culbert, Andria L.; Convente, Michael R.; Caron, Robert J.; Wright, Alexander C.; Maidment, Andrew D.A.; Kaplan, Frederick S.; Shore, Eileen M.

2013-01-01

Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of dysregulated cellular differentiation characterized by malformation of the great toes during embryonic skeletal development and by progressive heterotopic endochondral ossification post-natally. Patients with these classic clinical features of FOP have the identical heterozygous single nucleotide substitution (c.617G>A; R206H) in the gene encoding ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. Gene targeting was used to develop a knock-in mouse model for FOP (Acvr1R206H/+). Radiographic analysis of Acvr1R206H/+ chimeric mice revealed that this mutation induced malformed first digits in the hind limbs and post-natal extra-skeletal bone formation, recapitulating the human disease. Histological analysis of murine lesions showed inflammatory infiltration and apoptosis of skeletal muscle followed by robust formation of heterotopic bone through an endochondral pathway, identical to that seen in patients. Progenitor cells of a Tie2+ lineage participated in each stage of endochondral osteogenesis. We further determined that both wild-type and mutant cells are present within the ectopic bone tissue, an unexpected finding that indicates that although the mutation is necessary to induce the bone formation process, the mutation is not required for progenitor cell contribution to bone and cartilage. This unique knock-in mouse model provides novel insight into the genetic regulation of heterotopic ossification and establishes the first direct in vivo evidence that the R206H mutation in ACVR1 causes FOP. PMID:22508565

Radiologic evaluation after posterior instrumented surgery for thoracic ossification of the posterior longitudinal ligament: union between rostral and caudal ossifications.

PubMed

Ando, Kei; Imagama, Shiro; Ito, Zenya; Kobayashi, Kazuyoshi; Ukai, Junichi; Muramoto, Akio; Shinjo, Ryuichi; Matsumoto, Tomohiro; Nakashima, Hiroaki; Ishiguro, Naoki

2014-05-01

Retrospective clinical study. To investigate, using multislice CT images, how thoracic ossification of the posterior longitudinal ligament (OPLL) changes with time after thoracic posterior fusion surgery. Few studies have evaluated thoracic OPLL preoperatively and post using computed tomography (CT). The subjects included 19 patients (7 men and 12 women) with an average age at surgery of 52 years (38-66 y) who underwent indirect posterior decompression with corrective fusion and instrumentation at our institute. Minimum follow-up period was 1 year, and averaged 3 years 10 months (12-120 mo). Using CT images, we investigated fusion range, preoperative and postoperative Cobb angles of thoracic fusion levels, intraoperative and postoperative blood loss, operative time, hyperintense areas on preoperative MRI of thoracic spine and thickness of the OPLL on the reconstructed sagittal, multislice CT images taken before the operation and at 3 months, 6 months and 1 year after surgery. The basic fusion area was 3 vertebrae above and below the OPLL lesion. The mean operative time was 7 hours and 48 min (4 h 39 min-10 h 28 min), and blood loss was 1631 mL (160-11,731 mL). Intramedullary signal intensity change on magnetic resonance images was observed at the most severe ossification area in 18 patients. Interestingly, the rostral and caudal ossification regions of the OPLLs, as seen on sagittal CT images, were discontinuous across the disk space in all patients. Postoperatively, the discontinuous segments connected in all patients without progression of OPLL thickness by 5.1 months on average. All patients needing surgery had discontinuity across the disk space between the rostral and caudal ossified lesions as seen on CT. This discontinuity was considered to be the main reason for the myelopathy because a high-intensity area on magnetic resonance imaging was seen in 18 of 19 patients at the same level. Rigid fixation with instrumentation may allow the discontinuous segments

Digital image analysis of ossification centers in the axial dens and body in the human fetus.

PubMed

Baumgart, Mariusz; Wiśniewski, Marcin; Grzonkowska, Magdalena; Małkowski, Bogdan; Badura, Mateusz; Dąbrowska, Maria; Szpinda, Michał

2016-12-01

The detailed understanding of the anatomy and timing of ossification centers is indispensable in both determining the fetal stage and maturity and for detecting congenital disorders. This study was performed to quantitatively examine the odontoid and body ossification centers in the axis with respect to their linear, planar and volumetric parameters. Using the methods of CT, digital image analysis and statistics, the size of the odontoid and body ossification centers in the axis in 55 spontaneously aborted human fetuses aged 17-30 weeks was studied. With no sex difference, the best fit growth dynamics for odontoid and body ossification centers of the axis were, respectively, as follows: for transverse diameter y = -10.752 + 4.276 × ln(age) ± 0.335 and y = -10.578 + 4.265 × ln(age) ± 0.338, for sagittal diameter y = -4.329 + 2.010 × ln(age) ± 0.182 and y = -3.934 + 1.930 × ln(age) ± 0.182, for cross-sectional area y = -7.102 + 0.520 × age ± 0.724 and y = -7.002 + 0.521 × age ± 0.726, and for volume y = -37.021 + 14.014 × ln(age) ± 1.091 and y = -37.425 + 14.197 × ln(age) ± 1.109. With no sex differences, the odontoid and body ossification centers of the axis grow logarithmically in transverse and sagittal diameters, and in volume, while proportionately in cross-sectional area. Our specific-age reference data for the odontoid and body ossification centers of the axis may be relevant for determining the fetal stage and maturity and for in utero three-dimensional sonographic detecting segmentation anomalies of the axis.

Characterization of ossification of the posterior rim of acetabulum in the developing hip and its impact on the assessment of femoroacetabular impingement.

PubMed

Morris, William Z; Chen, Jason Y; Cooperman, Daniel R; Liu, Raymond W

2015-02-04

Many radiographic indices that are used to assess adolescents for femoroacetabular impingement rely on an ossified posterior acetabular wall. A recent study identified a secondary ossification center in the posterior rim of the acetabulum, the ossification of which may affect perceived acetabular coverage. The purpose of this study was to characterize ossification of the posterior rim of the acetabulum with use of a longitudinal radiographic study and quantify its impact on the radiographic assessment of femoroacetabular impingement. In this study, we utilized a historical collection of annual radiographs made in a population of healthy adolescents. Six hundred and twelve anteroposterior radiographs of the left hip of ninety-eight patients were reviewed to identify the appearance, duration, and fusion of the secondary ossification center in the posterior rim of the acetabulum. The center-edge angle was then measured before appearance and after fusion of the secondary ossification center in a subset of ten patients who had <5° of rotation on all radiographs. The secondary ossification center in the posterior rim was identified in seventy-three of the ninety-eight subjects, with no significant difference between the sexes. The mean patient age at the time of radiographic appearance of this secondary ossification center was fourteen years for males and twelve years for females. The mean duration of radiographic appearance was ten months for both sexes. Serial center-edge angles were measured in a subset of ten patients, and they increased during posterior rim ossification by a mean of 4.1°. The secondary ossification center in the posterior rim of the acetabulum (the posterior rim sign) is a common radiographic finding that reliably appears for ten months around the time of triradiate closure. Posterior rim ossification led to a mean increase of 4° of perceived acetabular coverage through the center-edge angle. Given the narrow margin between normal coverage (33�

Thoracic myelopathy caused by ossification of the ligamentum flavum: a report of 18 cases.

PubMed

Ben Hamouda, Karim; Jemel, Hafedh; Haouet, Slim; Khaldi, Moncef

2003-09-01

Thoracic myelopathy caused by ossification of the ligamentum flavum (OLF) is a rare entity, most evident in Japan. The authors studied the clinical manifestations, radiological aspects, surgical treatment, and pathogenesis of this disease. Eighteen patients with OLF-induced thoracic myelopathy underwent laminectomy. The severity of myelopathy varied. Complete paraplegia was seen in three cases. Compression of the upper and middle third of the thoracic spine was evident in six cases and of the lower third in 12 cases. Multilevel OLF was demonstrated in 13 cases. In most cases, the ossified ligamentum flavum appears as a V-shaped lesion on computerized tomography and magnetic resonance images. In all patients the diameter of the posterior spinal canal, already narrowed, was further exacerbated by the OLF. Laminectomy was limited to the levels of compression, and the ligamentum flavum was resected in all cases. The symptoms and signs improved in 13 cases and stabilized in four cases. In one case symptoms recurred as a result of ossified lesions forming at other sites. Histological examination showed that the mode of development of the ossified ligaments was endochondral ossification. Reports of OLF-induced myelopathy are rare and mainly described in Japan. The incidence also seems high in North Africa. An early laminectomy limited to the level of compression is recommended. Ossified ligamentum flavum is different from the calcification of the ligamentum flavum, which is due to crystal deposits.

Hinged external fixation of the elbow.

PubMed

Chen, Neal C; Julka, Abhishek

2010-08-01

Hinged external fixation of the elbow provides the advantages of static fixation with the benefits of continued motion through the joint. Indications for the use of this method of fixation include traumatic instability, distraction interposition arthroplasty, instability after contracture release, and instability after excision of heterotopic ossification. Orthopedic surgeons should be familiar with hinged fixators and their application when faced with an unstable ulnohumeral joint. 2010 Elsevier Inc. All rights reserved.

MEMO1 drives cranial endochondral ossification and palatogenesis

PubMed Central

Otterloo, Eric Van; Feng, Weiguo; Jones, Kenneth L; Hynes, Nancy E; Clouthier, David E; Niswander, Lee; Williams, Trevor

2016-01-01

The cranial base is a component of the neurocranium and has a central role in the structural integration of the face, brain and vertebral column. Consequently, alteration in the shape of the human cranial base has been intimately linked with primate evolution and defective development is associated with numerous human facial abnormalities. Here we describe a novel recessive mutant mouse strain that presented with a domed head and fully penetrant cleft secondary palate coupled with defects in the formation of the underlying cranial base. Mapping and non-complementation studies revealed a specific mutation in Memo1 - a gene originally associated with cell migration. Expression analysis of Memo1 identified robust expression in the perichondrium and periosteum of the developing cranial base, but only modest expression in the palatal shelves. Fittingly, although the palatal shelves failed to elevate in Memo1 mutants, expression changes were modest within the shelves themselves. In contrast, the cranial base, which forms via endochondral ossification had major reductions in the expression of genes responsible for bone formation, notably matrix metalloproteinases and markers of the osteoblast lineage, mirrored by an increase in markers of cartilage and extracellular matrix development. Concomitant with these changes, mutant cranial bases showed an increased zone of hypertrophic chondrocytes accompanied by a reduction in both vascular invasion and mineralization. Finally, neural crest cell-specific deletion of Memo1 caused a failure of anterior cranial base ossification indicating a cell autonomous role for MEMO1 in the development of these neural crest cell derived structures. However, palate formation was largely normal in these conditional mutants, suggesting a non-autonomous role for MEMO1 in palatal closure. Overall, these findings assign a new function to MEMO1 in driving endochondral ossification in the cranium, and also link abnormal development of the cranial base

Risks of secondary malignancies with heterotopic bone radiation therapy for patients younger than 40 years

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

Cadieux, Catherine L., E-mail: ccadieux@umail.iu.edu; DesRosiers, Colleen; McMullen, Kevin

Heterotopic ossification (HO) of the bone is defined as a benign condition in which abnormal bone formation occurs in soft tissue. One of the most common prophylactic treatments for HO is radiation therapy (RT). This study retrospectively reviewed 20 patients younger than the age of 40 who received radiation to prevent HO in a single fraction of 7 Gray. The purpose of this study is to assess the risk of a second malignancy in these patients by recreating their treatment fields and contouring organs at risk to estimate the radiation dose absorbed by normal tissues outside the radiation treatment field.more » Diagnostic computed tomography (CT) scans for each patient were used to recreate treatment fields and to calculate dose to structures of interest. The distance from the field edge to each structure and its depth was recorded. Dose measurements in a water phantom were performed for the range of depths, distances, and field sizes used in the actual treatment plans. Computer-generated doses were compared to estimates based on measurement. The structure dose recorded was the higher dose generated between the 2 methods. Scatter dose was recorded to the rectum, bladder, sigmoid colon, small bowel, ovaries and utero-cervix in female patients, and prostate and gonads in male patients. In some patients, there is considerable dose received by certain organs from scatter because of their proximity to the radiation field. The average dose to the ovarian region was 4.125 Gy with a range of 1.085 to 6.228 Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible.« less

Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese

PubMed Central

Zhang, Yunzhi; Liu, Haiyan; Zhang, Chen; Zhang, Tianxiao; Zhang, Bo; Li, Lu; Chen, Gang; Fu, Dongke; Wang, KunZheng

2015-01-01

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5’ end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels. PMID:26568273

Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.

PubMed

Zhang, Yunzhi; Liu, Haiyan; Zhang, Chen; Zhang, Tianxiao; Zhang, Bo; Li, Lu; Chen, Gang; Fu, Dongke; Wang, KunZheng

2015-11-16

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

Anterior approach versus posterior approach for Pipkin I and II femoral head fractures: A systemic review and meta-analysis.

PubMed

Wang, Chen-guang; Li, Yao-min; Zhang, Hua-feng; Li, Hui; Li, Zhi-jun

2016-03-01

We performed a meta-analysis, pooling the results from controlled clinical trials to compare the efficiency of anterior and posterior surgical approaches to Pipkin I and II fractures of the femoral head. Potential academic articles were identified from the Cochrane Library, Medline (1966-2015.5), PubMed (1966-2015.5), Embase (1980-2015.5) and ScienceDirect (1966-2015.5) databases. Gray studies were identified from the references of the included literature. Pooling of the data was performed and analyzed by RevMan software, version 5.1. Five case-control trials (CCTs) met the inclusion criteria. There were significant differences in the incidence of heterotopic ossification (HO) between the approaches, but no significant differences were found between the two groups regarding functional outcomes of the hip, general postoperative complications, osteonecrosis of the femoral head or post-traumatic arthritis. The present meta-analysis indicated that the posterior approach decreased the risk of heterotopic ossification compared with the anterior approach for the treatment of Pipkin I and II femoral head fractures. No other complications were related to anterior and posterior approaches. Future high-quality randomized, controlled trials (RCTs) are needed to determine the optimal surgical approach and to predict other postoperative complications. III. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Wistar rats immature testicular tissue vitrification and heterotopic grafting.

PubMed

Benvenutti, Larissa; Salvador, Rafael Alonso; Til, David; Senn, Alfred Paul; Tames, David Rivero; Amaral, Nicole Louise Lângaro; Amaral, Vera Lúcia Lângaro

2018-04-25

To evaluate the efficiency of two vitrification protocols for rat immature testicular tissue and heterotopic transplantation. Twenty-four pre-pubertal Wistar rats were divided into three groups (n=8). After orchiectomy, testicular fragments (3mm) from Groups 1 and 2 were vitrified with different cryoprotectant concentration solutions, using sterile inoculation loops as support. After warming up, the fragments were submitted to cell viability assessment by Trypan blue and histological evaluation. Vitrified (Groups 1 and 2) and fresh (Group 3) fragments were grafted to the animals periauricular region. After 8 weeks of grafting, the implant site was histologically analyzed. The viability recovery rate from Group 1 (72.09%) was higher (p=0.02) than that from Group 2 (59.19%). Histological analysis showed similar tubular integrity between fresh fragments from Groups 1 and 3. Group 2 samples presented lower tubular integrity. We ran histological analyses in the grafts from the Groups. In all groups, it was possible to see the implant site, however, no fragment of testicular tissue or signs of inflammation were histologically found in most samples from Groups 1 and 3. In one sample from Group 2, we found degenerated seminiferous tubules with necrosis and signs of an inflammatory process. In another sample from Group 2, we found seminiferous tubules in the implant site. The vitrification of pre-pubertal testicular tissue of rats showed little damage to cell viability through histological analysis when we used cryoprotectants in a lower concentration. Heterotopic transplantation could not preserve the structural organization of the testicular tissue.

Transcriptomics provides mechanistic indicators of fluoride toxicology on endochondral ossification in the hind limb of Bufo gargarizans.

PubMed

Chao, Wu; Zhang, Yuhui; Chai, Lihong; Wang, Hongyuan

2018-06-10

Endochondral ossification, the process by which most of the bone is formed, is regulated by many specific groups of molecules and extracellular matrix components. Hind limb of Bufo gargarizans is a model to study endochondral ossification during metamorphosis. Chinese toad (Bufo gargarizans) were exposed to different fluoride concentrations (0, 1, 5, 10 and 20 mg L -1 ) from G3 to G42. The development of hind limb of B. gargarizans was observed using the double staining methodology. The transcriptome of hind limb of B. gargarizans was conducted using RNA-seq approach, and differentially expressed gene was also validated. In addition, the location of Sox9 and Ihh in the growth cartilage was determined using in situ hybridization. Our results showed that 5 mg L -1 stimulated bone mineralization, while 10 and 20 mg L -1 exposure could inhibit the tibio-fibula, tarsus and metacarpals ossification. Besides, 10 mg F/L treatment could down-regulate Ihh, Sox9, D2, D3, TRα, TRβ, Wnt10, FGF3 and BMP6 expression, while up-regulate ObRb and HHAT mRNA expression in the hind limb of B. gargarizans. Transcript level changes of Ihh, Sox9, D2, D3, TRα, TRβ, Wnt10, FGF3 and BMP6 were consistent with the results of RT-qPCR. In situ hybridization revealed that Ihh was expressed in prehypertrophic chondrocytes, while Sox9 was abundantly expressed in proliferous, prehypertrophic and hypertrophic chondrocytes. However, 10 mg F-/L did not cause any affect in the location of the Ihh and Sox9 mRNA. Therefore, high concentration of fluoride could affect the ossification-related genes mRNA expression and then inhibit the endochondral ossification. The present study thus will greatly contribute to our understanding of the effect of environmental contaminant on ossification in amphibian. Copyright © 2018 Elsevier B.V. All rights reserved.

Review of Heterotopic Thyroid Autotransplantation

PubMed Central

Sakr, Mahmoud; Mahmoud, Ahmed

2017-01-01

Total thyroidectomy is increasingly accepted for the management of bilateral benign thyroid disorders. Postoperatively, patients require lifelong levothyroxine replacement therapy to avoid postoperative hypothyroidism, which besides the burden of compliance, has been proven to be associated with several long-term side effects. Heterotopic thyroid autotransplantation was proposed several decades ago to avoid the need for life-long postoperative replacement therapy with maintaining the autoregulatory mechanism of thyroxin production inside the body according to its needs. Available data regarding this topic in literature is relatively poor. Before applying thyroid autotransplantation on humans, several studies have been done on animals, where the autologous transplantations were found to be successful in almost all the cases, proved by follow up postoperative 8-week measurements of thyroid hormones and histopathological examination of the removed autografts. Regarding the clinical application, few trials have been done using cryopreserved in vivo, in vitro or immediately autotransplanted thyroid autografts. Satisfactory results were obtained, however, the number of these studies and the number of patients per each study was very low. Besides the study methodologies were not so consistent. PMID:28535579

Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

PubMed

Prisby, Rhonda D

2014-07-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the

Heterotopic Prostate at Autopsy- An Unusual Mass at the Dome of the Urinary Bladder.

PubMed

Munde, Shital; Fernandes, Gwendolyn; Phadnis, Priyanka

2017-09-01

Heterotopic prostate in the dome of the urinary bladder is extremely rare and difficult to diagnose. It is often mistaken for neoplastic masses and histopathological examination is warranted for diagnosis. We report an autopsy case of an ectopic prostate at the dome of the bladder which mimicked a neoplasm on gross pathology.

A Rare Case of Heterotopic Pregnancy with Ruptured Left Rudimentary Horn Pregnancy

PubMed Central

Rathod, Setu

2015-01-01

Heterotopic pregnancy(HP) occurs when intrauterine and ectopic pregnancies coexist. We report a case of HP at 14 wk of gestation presenting as ruptured left rudimentary horn ectopic pregnancy with live intrauterine gestation and was managed with emergency laparotomy followed by resection of left rudimentary non communicating horn of uterus. The intrauterine pregnancy continued uneventfully. A female baby was delivered vaginally at 41 wk following induction of labour. PMID:25954670

Long-term follow-up for ossification of autologous bone plug and skin sinking after periosteum-preserved burr hole surgery.

PubMed

Kubota, Hisashi; Sanada, Yasuhiro; Murakami, Saori; Miyauchi, Masaharu; Iwakura, Michihiro; Nagatsuka, Kazuhiro; Furukawa, Kentaro; Kato, Amami; Fujita, Mitsugu

2017-01-01

The demand of a burr hole surgery for chronic subdural hematoma (CSDH) is increasing in the global aging society. Burr hole-derived autologous bone dusts are not associated with extra costs compared with other commonly used synthetic materials. In addition, postoperative calvarium ossification requires periosteum-mediated blood supply, which is lacking after using avascular synthetic materials. Based on these findings, we hypothesized that the combination of the bone plugs and the preserved periosteum during burr hole surgeries for CSDH would induce efficient calvarium ossification. We evaluated the long-term effects of bone plugs on the degree of ossification and cosmetic appearance of the skin covering the burr hole sites. We included 8 patients (9 burr holes) who received the autologous bone dust derived from burr holes. As the control group, 9 burr holes that did not receive any burr hole plugs were retrospectively selected. These burr holes were evaluated by computed tomography (CT) scan for the calvarium defect ratios, CT value-based ossification, and the degree of skin sinking. Ossification was observed in all the bone plugs by the bone density CT scans; they maintained their volume at 12 months after the surgeries. The calvarium defect ratios (volume ratios of the unossified parts in the burr holes) gradually increased during the first 6 months and reached 0.44 at 12 months. The mean CT values also increased from 527 HU to 750 HU for the first 6 months and reached 905 HU at 12 months. The degrees of skin sinking at the burr hole sites with the bone plugs were 1.24 mm whereas those without the bone plugs were 2.69 mm ( P = 0.004). Application of burr hole-derived autologous bone dust is associated with better ossification and objective cosmetic result following burr hole surgery after CSDH.

Heterotopic Prostate at Autopsy- An Unusual Mass at the Dome of the Urinary Bladder

PubMed Central

Munde, Shital; Phadnis, Priyanka

2017-01-01

Heterotopic prostate in the dome of the urinary bladder is extremely rare and difficult to diagnose. It is often mistaken for neoplastic masses and histopathological examination is warranted for diagnosis. We report an autopsy case of an ectopic prostate at the dome of the bladder which mimicked a neoplasm on gross pathology. PMID:29207717

Early treatment with the von Rosen splint for neonatal instability of the hip is safe regarding avascular necrosis of the femoral head

PubMed Central

Wenger, Daniel; Samuelsson, Hanna; Düppe, Henrik; Tiderius, Carl Johan

2016-01-01

Background and purpose — Avascular necrosis of the femoral head (AVN) is a complication in treatment of developmental dysplasia of the hip (DDH). We evaluated the risk of AVN after early treatment in the von Rosen splint and measured the diameter of the ossific nucleus at 1 year of age. Children and methods — All children born in Malmö, Sweden, undergo clinical screening for neonatal instability of the hip (NIH). We reviewed 1-year radiographs of all children treated early for NIH in our department from 2003 through 2010. The diameter of the ossific nucleus was measured, and signs of AVN were classified according to Kalamchi-MacEwen. Subsequent radiographs, taken for any reason, were reviewed and a local registry of diagnoses was used to identify subsequent AVN. Results — 229 of 586 children referred because of suspected NIH received early treatment (age ≤ 1 week) for NIH during the study period. 2 of the 229 treated children (0.9%, 95% CI: 0.1–3.1) had grade-1 AVN. Both had spontaneous resolution and were asymptomatic during the observation time (6 and 8 years). 466 children met the inclusion criteria for measurement of the ossific nucleus. Neonatally dislocated hips had significantly smaller ossific nuclei than neonatally stable hips: mean 9.4 mm (95% CI: 9.1–9.8) vs. 11.1 mm (95% CI: 10.9–11.3) at 1 year (p < 0.001). Interpretation — Early treatment with the von Rosen splint for NIH is safe regarding AVN. The ossification of the femoral head is slower in children with NIH than in untreated children with neonatally stable hips. PMID:26730503

Spinal fusion for scoliosis in Rett syndrome with an emphasis on early postoperative complications.

PubMed

Gabos, Peter G; Inan, Muharrem; Thacker, Mihir; Borkhu, Buttugs

2012-01-15

Retrospective case-control study. To examine the postoperative complications of posterior spinal fusion in a population of patients with Rett syndrome (RS). Scoliosis is a common feature of RS, a progressive neurologic disorder affecting almost exclusively females. Despite this, there is little published information regarding the surgical treatment of scoliosis in this disorder. Sixteen consecutive female patients with RS treated by posterior spinal fusion and unit rod instrumentation for progressive scoliosis between 1995 and 2003 were evaluated. Only patients with a minimum of 2-year follow-up were included. Preoperative medical conditions and postoperative complications were recorded. As a control group, we randomly selected 32 spastic quadriplegic patients who underwent the identical procedure during the same time period, selected from our database and matched according to age, level of neurologic impairment, and medical complexity. There was a high rate of early medical complications in the RS patients, with 28 major and 37 minor complications. Only 1 patient did not have a major medical complication, and every patient had at least 1 minor gastrointestinal and/or respiratory complication. Major respiratory complications occurred in 10 patients (63%) and comprised 61% of all major complications. Major gastrointestinal complications occurred in 6 patients (37%) and comprised 21% of all major complications. Other major complications included disseminated intravascular coagulopathy (1 patient), subacute bacterial endocarditis (1 patient), sacral decubiti requiring surgical debridement (2 patients), and extensive bilateral heterotopic ossification of the hips (1 patient). There were no cases of instrumentation failure, pseudarthrosis, deep infection, or need for rod revision. Postoperative complication scores were similar to those in patients with spastic quadriplegic pattern cerebral palsy. Spinal fusion for scoliosis in RS can give a satisfactory technical result

Shaping the military wound: issues surrounding the reconstruction of injured servicemen at the Royal Centre for Defence Medicine

PubMed Central

Evriviades, Demetrius; Jeffery, Steven; Cubison, Tania; Lawton, Graham; Gill, Martin; Mortiboy, Deborah

2011-01-01

The conflict in Afghanistan has produced injuries similar to those produced from military conflicts for generations. What distinguishes the modern casualty of the conflict in Afghanistan from those of other conflicts is the effectiveness of modern field medical care that has led to individuals surviving with injuries, which would have been immediately fatal even a few years ago. These patients present several challenges to the reconstructive surgeon. These injured individuals present early challenges of massive soft-tissue trauma, unstable physiology, complex bony and soft-tissue defects, unusual infections, limited reconstructive donor sites, peripheral nerve injuries and traumatic amputations. Late challenges to rehabilitation include the development of heterotopic ossification in amputation stumps. This paper outlines the approach taken by the reconstructive team at the Royal Centre for Defence Medicine in managing these most difficult of reconstructive challenges. PMID:21149357

Thinking Meillassoux's Factiality: A Pedagogical Movement against Ossification of Bodymind

ERIC Educational Resources Information Center

Oral, Sevket Benhur

2015-01-01

This article is about a pedagogical movement I discern in Quentin Meillassoux's ontology. The goal of the essay is to introduce his approach to reality in outline form and offer it as a possible route to conceptualize education as the practice of keeping the bodymind attentive and agile against its unsound ossification by way of providing a…

Lethal short-limbed chondrodysplasia in early infancy.

PubMed

Yang, S S; Heidelberger, K P; Brough, A J; Corbett, D P; Bernstein, J

1976-01-01

Nineteen cases of chondrodysplastic short-limbed dwarfism in early infancy were studied in the context of current clinical classification based on established radiographic criteria. The histopathologic findings were sufficiently distinctive in most categories to provide additional diagnostic criteria and to contribute to the understanding and delineation of these disorders. 1. Homozygous achondroplasia is distinguished by markedly disturbed endochondral ossification that differs from the pattern seen in typical heterozygous achondroplasia. The physeal chondrocytes contain abundant granules of glycogen. 2. Achondrogenesis, the severest form of chondrodysplasia, exists in 2 types, in which the histopathologic findings appear to be distinctive and diagnostic. Type 1 is characterized by severe disturbance in endochondral ossification. The zone of resting cartilage contains relatively normal matrix, and the chondrocytes contain intracytoplasmic inclusions. The cartilaginous matrix in type 2 is markedly deficient, and the chondrocytes have a large, primitive, mesenchymatous appearance. 3. Thanatophoric dwarfism is associated with disorganized endochondral ossification similar to that in homozygous achondroplasia, but there is no accumulation of glycogen within chondrocytes. Type 2 thanatophoric dwarfism is differentiated from classical type 1 by the presence of cloverleaf skull and histologically by many bone-lined, penetrating vascular canals in the physis and by hyperactive osteoblasts and osteoclasts in the metaphysis. 4. Asphyxiating thoracic dysplasia of Jeune is differentiated histologically into 2 types. Type 1 is characterized by patchy distribution of endochondral ossification in the physis, irregular physeal-metaphyseal junction and large islands of poorly mineralized cartilage in the metaphysis. Type 2 is characterized by uniform distribution of endochondral ossification that is disorganized and is accompanied by advancing cartilage forming latticelike

Developmental anomaly of ossification type patella partita.

PubMed

Oohashi, Yoshikazu

2015-04-01

Bipartite patella has been recognized as an incidental radiographic finding. However, symptomatic bipartite patella is occasionally diagnosed in adolescents and young athletes. The incidence of bipartite patella has been reported at 0.2-1.7, and 1-2 % of these cases are symptomatic. The purpose of this review article was to discuss current concepts relevant to developmental anomaly of ossification type patella partita. A PubMed database search using the key words "bipartite patella" was performed. Clinical papers reporting the bipartite patella were included. Four German-language studies were also included, three for incidence of bipartite patella and one for classification. A new classification of developmental anomaly of ossification type patella partita based on location and number of fragment was recently proposed. It is simple and useful and applicable to all types of bipartite or tripartite patella. Several imaging studies have reportedly been used to evaluate symptomatic bipartite patella. MRI is currently the most appropriate method used to assess patients with bipartite patella. Although surgical procedures have been developed that reduce excessive traction force by the vastus lateralis muscle on the bipartite fragment, there is not sufficient evidence to support their use for routine treatment of painful bipartite patella. In most symptomatic cases, movement at the interface between the bipartite fragment and the body of the patella presumably causes the pain. Therefore, the existence of apparent motion at the interface should be confirmed by specific imaging studies before surgery. Magnetic resonance imaging findings may provide such evidence by demonstrating a fluid bright signal across the segmentation, typical of pseudoarthrosis. V.

Mechanisms and Treatments of Heterotopic Ossification Following Spinal Cord Injuries

DTIC Science & Technology

2016-10-01

tissues  from  the  completed etanercept and GW2580 experiments are being processed for  immunohistology to  stain  for  markers of M1 and M2...a defined  area of the muscle. We observed that HO developed only if the mechanical damage was combined with  injection of  Gram ‐negative bacterial... staining  on archival sections of mouse hind limb muscles  generated prior to this award. As illustrated in Figure 4, we are able to successfully  stain

The Contribution of Genotype to Heterotopic Ossification after Orthopaedic Trauma

DTIC Science & Technology

2010-05-01

factor H variant increases the risk of age - related macular degeneration . Science 2005 Apr 15;308(5720):419-21. (8) Lowik CW, van Bezooijen RL. Wnt...patients including: o ISS o Head AIS o Number ICU days o Ventilator Days o Ventilator Assisted Pneumonia o Age o Race o Gender • Manuscript submitted to...is summarized in Table 1.  HO (1=y, 0=n)  N  Mean  STD  P value  AGE   0  1181 41.78 18.51 0.443  1  113 42.14 16.17 ISS  0  1182 26.02 12.58 .0223  1

Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

PubMed Central

Prisby, Rhonda D.

2014-01-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p <0.05) in old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p <0.05) 262%, 375% and 263%, respectively, in old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in “microvascular dead space” in regards to loss of patency and vasomotor function as opposed to necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the

Eccentric Capitellar Ossification Limits the Utility of the Radiocapitellar Line in Young Children.

PubMed

Fader, Lauren M; Laor, Tal; Eismann, Emily A; Cornwall, Roger; Little, Kevin J

2016-03-01

The radiocapitellar line (RCL) has long been used for the radiographic evaluation of elbow alignment. In children, the capitellar ossific nucleus serves as a proxy for the entire capitellum, but this substitution has not been verified. Using magnetic resonance imaging (MRI), we sought to understand how maturation of the ossific nucleus of the capitellum affects the utility of RCL throughout skeletal maturation of the elbow. The RCL was drawn on coronal and sagittal MRIs in 82 children (43 boys, 39 girls; age range, 1 to 13 y) with at least 3 patients in each 1-year interval age group. The perpendicular distance of the RCL from the center of both the cartilaginous capitellum and the capitellar ossific nucleus was measured relative to its total width, and a percent offset for each measurement was calculated. Logarithmic regression analysis was performed to analyze the effect of age and sex on percent offset. The RCL reliably intersected with the central third of the cartilaginous capitellum at all ages in both planes. Although the RCL intersected with the ossified capitellum in all but 3 measurements, it intersected with the central third of the ossified capitellum less often in younger children in both sagittal (B=0.47, P<0.001) and coronal (B=0.31, P=0.002) planes. Percent offset decreased significantly with age in a logarithmic manner in both sagittal (r=0.57, P<0.001) and coronal (r=-0.47, P<0.001) planes. 95% confidence intervals predict that the sagittal plane RCL will accurately intersect the central third of the ossified capitellum by age 10 years in girls and age 11 years in boys but not in the coronal plane. Eccentric ossification of the capitellum explains RCL variability in young children. The RCL does not reliably intersect the central third of the ossified capitellum until ages 10 years in girls and 11 years in boys in the sagittal plane. The RCL should be used within its limitations in skeletally immature children and should be combined with advanced

Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification

PubMed Central

Liu, Li; Liu, Zhi-zhong; Chen, Hui; Zhang, Guo-jun; Kong, Yu-hua; Kang, Xi-xiong

2011-01-01

Aim: To investigate the ability of ox-LDL to induce ossification of endothelial progenitor cells (EPCs) in vitro and explored whether oxidative stress, especially hypoxia inducible factor-1α (HIF-1α) and reactive oxygen species (ROS), participate in the ossific process. Methods: Rat bone marrow-derived endothelial progenitor cells (BMEPCs) were cultured in endothelial growth medium supplemented with VEGF (40 ng/mL) and bFGF (10 ng/mL). The cells were treated with oxidized low-density lipoprotein (ox-LDL, 5 μg/mL) and/or β-glycerophosphate (β-GP, 10 mmol/L). Calcium content and Von Kossa staining were used as the measures of calcium deposition. Ossific gene expression was determined using RT-PCR. The expression of osteocalcin (OCN) was detected with immunofluorescence. Alkaline phosphatase (ALP) activity was analyzed using colorimetric assay. Intercellular reactive oxygen species (ROS) were measured with flow cytometry. Results: BMEPCs exhibited a spindle-like shape. The percentage of cells that expressed the cell markers of EPCs CD34, CD133 and kinase insert domain-containing receptor (KDR) were 46.2%±5.8%, 23.5%±4.0% and 74.3%±8.8%, respectively. Among the total cells, 78.3%±4.2% were stained with endothelial-specific fluorescence. Treatment of BMEPCs with ox-LDL significantly promoted calcium deposition, which was further significantly enhanced by co-treatment with β-GP. The same treatments significantly increased the gene expression of core-binding factor a-1 (cbfa-1) and OCN, while decreased the gene expression of osteoprotegerin (OPG). The treatments also significantly enhanced the activity of ALP, but did not affect the number of OCN+ cells. Furthermore, the treatments significantly increased ROS and activated the hypoxia inducible factor-1α (HIF-1α). In all these effects, ox-LDL acted synergistically with β-GP. Conclusion: Ox-LDL and β-GP synergistically induce ossification of BMEPCs, in which an oxidizing mechanism is involved. PMID:22036865

Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification.

PubMed

Liu, Li; Liu, Zhi-zhong; Chen, Hui; Zhang, Guo-jun; Kong, Yu-hua; Kang, Xi-xiong

2011-12-01

To investigate the ability of ox-LDL to induce ossification of endothelial progenitor cells (EPCs) in vitro and explored whether oxidative stress, especially hypoxia inducible factor-1α (HIF-1α) and reactive oxygen species (ROS), participate in the ossific process. Rat bone marrow-derived endothelial progenitor cells (BMEPCs) were cultured in endothelial growth medium supplemented with VEGF (40 ng/mL) and bFGF (10 ng/mL). The cells were treated with oxidized low-density lipoprotein (ox-LDL, 5 μg/mL) and/or β-glycerophosphate (β-GP, 10 mmol/L). Calcium content and Von Kossa staining were used as the measures of calcium deposition. Ossific gene expression was determined using RT-PCR. The expression of osteocalcin (OCN) was detected with immunofluorescence. Alkaline phosphatase (ALP) activity was analyzed using colorimetric assay. Intercellular reactive oxygen species (ROS) were measured with flow cytometry. BMEPCs exhibited a spindle-like shape. The percentage of cells that expressed the cell markers of EPCs CD34, CD133 and kinase insert domain-containing receptor (KDR) were 46.2%±5.8%, 23.5%±4.0% and 74.3%±8.8%, respectively. Among the total cells, 78.3%±4.2% were stained with endothelial-specific fluorescence. Treatment of BMEPCs with ox-LDL significantly promoted calcium deposition, which was further significantly enhanced by co-treatment with β-GP. The same treatments significantly increased the gene expression of core-binding factor a-1 (cbfa-1) and OCN, while decreased the gene expression of osteoprotegerin (OPG). The treatments also significantly enhanced the activity of ALP, but did not affect the number of OCN(+) cells. Furthermore, the treatments significantly increased ROS and activated the hypoxia inducible factor-1α (HIF-1α). In all these effects, ox-LDL acted synergistically with β-GP. Ox-LDL and β-GP synergistically induce ossification of BMEPCs, in which an oxidizing mechanism is involved.

Efficacy of Nonsteroidal Anti-inflammatory Drug Prophylaxis for Heterotrophic Ossification in Hip Arthroscopy: A Systematic Review.

PubMed

Yeung, Marco; Jamshidi, Sahab; Horner, Nolan; Simunovic, Nicole; Karlsson, Jon; Ayeni, Olufemi R

2016-03-01

The purpose of this systematic review was to investigate the efficacy of nonsteroidal anti-inflammatory drug (NSAID) prophylaxis for preventing heterotopic ossification (HO) in the setting of hip arthroscopy. A systematic search was performed in duplicate for studies comparing the use of NSAID prophylaxis for HO in the setting of hip arthroscopy until March 2015. Study parameters--including sample size, incidence of HO, adverse effects, and level of symptoms--were obtained. Furthermore, the level of evidence of studies was collected and quality assessment was performed. The difference in incidence as well as pooled odds ratios were calculated and analyzed to compare no prophylaxis versus NSAID prophylaxis. This systematic review identified 5 studies, consisting of 1,662 patients, investigating NSAID prophylaxis in hip arthroscopy. HO was diagnosed with the use of postoperative hip radiographs at follow-up, with 95% of cases classified using the Brooker classification. The incidence of HO was 13.4% without NSAID prophylaxis and 3.3% with NSAID prophylaxis. Pooled odds ratios from the prospective studies were 0.07 (95% confidence interval [CI], 0.02 to 0.28; P = .0002; I(2) = 0%), showing with statistical significance that NSAID prophylaxis decreased the incidence of HO. The retrospective data similarly showed pooled odds ratios of 0.03 (95% CI, 0.00 to 1.43); P = .08; I(2) = 84%), although it was not statistically significant. Most of the patients who experienced HO in both groups were not reported to be symptomatic. Adverse effects and compliance were not consistently reported. The available orthopaedic literature suggests that the incidence of postoperative HO may be decreased with the use of NSAID prophylaxis in hip arthroscopy. However, the evidence is unclear regarding NSAID drug regimen choice, drug compliance, and adverse effects. Level III, systematic review of Level I, Level II, and Level III studies. Copyright © 2016 Arthroscopy Association of North

Early results of Latitude primary total elbow replacement with a minimum follow-up of 2 years.

PubMed

Mehta, Saurabh S; Watts, Adam C; Talwalkar, Sumedh C; Birch, Ann; Nuttall, David; Trail, Ian A

2017-10-01

The aim of this study was to present outcomes of primary Latitude total elbow replacement (TER) with a minimum follow-up of 2 years. A retrospective cohort study was undertaken with prospective outcome data collection for the latest outcome. Included were 63 consecutive primary Latitude TERs in 58 patients performed during a period of 5 years at a specialist orthopedic hospital. The mean age of the patients was 62 years (33-85 years). Five primary TERs (4 patients) were lost to follow-up. The primary diagnosis was rheumatoid arthritis in 49, osteoarthritis in 8, and trauma in 6 elbows. The mean flexion-extension arc was 75° preoperatively and 97° postoperatively. Mean postoperative Elbex pain score was 19/100, and function score was 37/100. Mean postoperative scores were 42/100 for the Quick Disabilities of the Arm, Shoulder, and Hand and 38/50 for the elbow-specific American Shoulder and Elbow Surgeons assessment. Four patients died of unrelated causes, and 8 of 63 underwent further surgical intervention, including explantation and conversion from unlinked to linked implant. On radiographic review of 41 surviving TERs, aseptic radiologic loosening was observed of the humeral component in 4 elbows and of the ulnar component in 9. Seven elbows had no radial component, and of the remaining 34 elbows, 16 (47%) had signs of loosening of the radial implant. Complications included 1 heterotopic ossification, 1 olecranon fracture, and 3 further procedures for ulnar nerve entrapment. The results indicate that the early outcome of Latitude TER is comparable to that of other prostheses. There is concern about early radiologic loosening of the radial component. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Esophageal motility and 24-h pH profiles of patients with heterotopic gastric mucosa in the cervical esophagus.

PubMed

Korkut, Esin; Bektaş, Mehmet; Alkan, Murat; Ustün, Yusuf; Meco, Cem; Ozden, Ali; Soykan, Irfan

2010-02-01

Heterotopic gastric mucosa occurs as a flat island of red mucosa in the proximal third of the esophagus where it gives rise to the cervical inlet patch. The aims of this study were to investigate the esophageal motility pattern and 24-h pH profiles of patients with cervical inlet patch. Thirty patients (16 women, mean age: 44.9 years, range: 23-72) diagnosed as having heterotopic gastric mucosa in the cervical esophagus with upper gastrointestinal symptoms had undergone esophageal motility testing and 24-h pH monitorisation with a double-channel pH probe. Manometric investigation was abnormal in 7 patients (non-specific esophageal motor disorder in 4 patients, esophageal hypomotility in 1 patient, and hypotensive LES in 2 patients). Pathological acid reflux (pH<4) was found in 9 (30%) of 30 heterotopic gastric mucosa patients during pH monitorisation from the distal probe. Pathological acid reflux in the proximal esophagus (percentage of total time of pH<4) was seen in four of these nine patients. Only four of the 30 patients (13.3%) presented with "acid independent episodes" during the 24-h esophageal pH monitorisation. Manometric investigation and 24-h pH monitorisation revealed that some of the patients with HGM have signs of esophageal motor dysfunction and "acid independent episodes" from the patches. These abnormalities may be responsible for some of the symptoms of HGM patients. Copyright 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

[Anterior Superior and Anterior Interior Iliac Spine Fractures. Comparison of the Results of Conservative and Surgical Treatment].

PubMed

Stančák, A; Kautzner, J; Havlas, V

2016-01-01

Avulsion fractures of the anterior superior iliac spine (ASIS) and anterior inferior iliac spine (AIIS) are rare injuries to the skeleton in children. They are most frequent in adolescent athletes, such as sprinters and long-distance runners, and football players. The authors present a group of patients treated at their department and compare the results of procedures used to manage different pelvic avulsion fractures. Between 2005 and 2012, 38 patients (31 boys and seven girls) with an average age of 15.1 years (range, 4-17 years) were treated. Fourteen patients with minimally displaced fractures were treated conservatively, 24 patients with fractures displaced more than 1 cm underwent surgery. All patients had a standard rehabilitation protocol. Post-operative assessments included: the range of motion in the hip; X-ray at 6 weeks, 3 months and 1 year; duration of bed rest; return to previous activities; occurrence of complications (heterotopic ossification, infection, etc). All patients returned to the pre-injury level of sports activities. Recovery was faster and early rehabilitation was better tolerated in patients treated surgically (p = 0.03), particularly in those with AIIS avulsion fractures. Ambulation with partial weight bearing was possible on average at 7.2 days (range, 2-10 days) in surgically treated patients and at 24.1 days (18-27 days) in conservatively treated patients; the difference was statistically significant (p = 0.02). The range of motion markedly improved in surgically treated patients as early as at 6 weeks while, in conservatively treated patients, the comparable outcome was achieved at 3 months of follow-up (p = 0.02). The time necessary for radiographic evidence of fragment union as well as full recovery was comparable in both patient groups. No deep wound infection was recorded; minor heterotopic ossification was detected in five patients, but no further treatment during follow-up was required. Indications for surgical treatment are

Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP).

PubMed

Brennan, Tracy A; Lindborg, Carter M; Bergbauer, Christian R; Wang, Haitao; Kaplan, Frederick S; Pignolo, Robert J

2018-04-01

Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies. Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Cromolyn, but not aprepitant, significantly decreases the total number of mast cells in FOP lesions. Furthermore, cromolyn specifically diminishes the number of degranulating and resting degranulated mast cells in pre-osseous lesions. This work demonstrates that consideration of FOP as a type of localized mastocytosis may offer new therapeutic interventions for treatment of this devastating condition. Copyright © 2017 Elsevier Inc. All rights reserved.

A radiographic study of the ossification of the posterior wall of the acetabulum: implications for the diagnosis of pediatric and adolescent hip disorders.

PubMed

Fabricant, Peter D; Hirsch, Brandon P; Holmes, Ian; Kelly, Bryan T; Lorich, Dean G; Helfet, David L; Bogner, Eric A; Green, Daniel W

2013-02-06

Subtle variations in acetabular morphology have been implicated in several pathologic hip conditions. Although it is understood that the acetabulum forms at the junction of the ilium, ischium, and pubis at the triradiate cartilage, the ossification and development pattern of the posterior wall of the acetabulum is unknown. Standard radiographs and computed tomographic scans used in evaluation of the adolescent hip do not allow a complete assessment of the non-ossified portions of the developing acetabulum. The purpose of this study was to define the currently unknown ossification pattern and development of the posterior wall of the acetabulum and to determine when conventional imaging, with use of computed tomography and radiographs, is appropriate. One hundred and eighty magnetic resonance imaging examinations in patients who were four to fifteen years old were evaluated by a musculoskeletal radiologist for ossification patterns of the posterior wall of the acetabulum and triradiate cartilage. Correlations were made with available radiographs. Posterior acetabular wall ossification lags behind anterior wall ossification throughout development. On average, the posterior wall of the acetabulum began to ossify at the chronological age of eight years, followed by a discrete rim of posterior calcification (posterior rim sign) at the patient age of twelve years, just prior to the fusion of the posterior acetabular wall elements to the pelvis. This preceded the closure of the triradiate cartilage in all subjects. On average, male patients had fusion of the posterior wall of the acetabulum one to 1.5 years after female patients. The ossification of the posterior wall of the acetabulum is completed in a predictable manner prior to closure of the triradiate cartilage.

β1/2 or M2/3 Receptors Are Required for Different Gastrointestinal Motility Responses Induced by Acupuncture at Heterotopic or Homotopic Acupoints

PubMed Central

Yu, Xiaochun; Cui, Changxiang; Yang, Zhaokun; Shi, Hong; Jing, Xianghong; Zhu, Bing

2016-01-01

Acupuncture at homotopic acupoints or heterotopic acupoints is known to either inhibit or facilitate gastrointestinal motility, depending on the acupoint location. However, little effort has been made to investigate the roles of specific receptors (such as adrenergic and muscarinic acetylcholine receptors) in mediating the effects of acupuncture at heterotopic and homotopic acupoints. Different adrenergic receptor subtypes or cholinergic receptor subtypes are predominantly expressed in various sections of the gut, resulting in variations between the effects of acupuncture at heterotopic or homotopic acupoints on gastrointestinal motility. Here, we investigated the role of β1/β2 receptors and M2/M3 receptors in gastrointestinal motility regulated by acupuncture at ST37, a heterotopic acupoint, and ST25, a homotopic acupoint, by simultaneously recording intraluminal pressures in the distal colon and stomach or jejunum and examining fecal phenol red excretion in β1/2 receptor-knockout mice and M2/3 receptor-knockout mice. We found that knockout of the M2/3 receptor significantly inhibited ST37 acupuncture-induced enhancement of gastric motility, jejunal motility, and colonic motility. Additionally, knocking out of the β1/2 receptor significantly diminished the ST25 acupuncture-induced inhibition of gastric motility and jejunal motility without significantly altering the enhancement of colonic motility induced by acupuncture at ST25. Acupuncture at ST37 significantly accelerated gastrointestinal transition in β1/2 receptor-knockout mice and their wild-type littermates. However, this acceleration of gastrointestinal transition was markedly diminished in M2/3 receptor-knockout mice relative to their wild-type littermates. Acupuncture at ST25 significantly increased gastrointestinal transition in β1/2 receptor-knockout mice and significantly decreased gastrointestinal transition in M2/3 receptor-knockout mice without altering gastrointestinal transition in wild

Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification

DTIC Science & Technology

2015-03-01

two thirds of these patients developing painful and debilitating HO. There are currently no effective treatments for HO other than surgical...prevention and treatment of HO, to relieve this painful and debilitating orthopaedic complication. American Society for Bone and Mineral Research, Houston...developing painful and debilitating HO. There are currently no effective treatments for HO other than surgical excision of the ossified tissue which

Bone Morphogenetic Protein Usage in Anterior Lumbar Interbody Fusion: What Else Can Go Wrong?

PubMed

Elias, Elias; Nasser, Zeina; Winegan, Lona; Verla, Terence; Omeis, Ibrahim

2018-03-01

Bone morphogenetic protein (BMP) graft showed promising outcome during early phases of its use. However, unreported adverse events and off-label use shattered its safe profile and raised concerns regarding its indication. In 2008 the U.S. Food and Drug Administration prohibited its use in anterior cervical spine procedures due to the possibility of edema, hematoma, and need to intubate. At the molecular level, BMPs act as multifactorial growth factors playing a role in cartilage, heart, and bone formation. However, its unfavorable effect on bone overgrowth or heterotopic ossification post spine surgeries has been described. Reported cases in the literature were limited to epidural bone formation. We present a rare and interesting case of a 59-year-old female, in whom BMP caused intradural bone growth several years after an anterior lumbar interbody fusion surgery. Caution must be exercised while using BMPs because of inadvertent complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Skeletal Morphogenesis of Microbrachis and Hyloplesion (Tetrapoda: Lepospondyli), and Implications for the Developmental Patterns of Extinct, Early Tetrapods

PubMed Central

Olori, Jennifer C.

2015-01-01

The ontogeny of extant amphibians often is used as a model for that of extinct early tetrapods, despite evidence for a spectrum of developmental modes in temnospondyls and a paucity of ontogenetic data for lepospondyls. I describe the skeletal morphogenesis of the extinct lepospondyls Microbrachis pelikani and Hyloplesion longicostatum using the largest samples examined for either taxon. Nearly all known specimens were re-examined, allowing for substantial anatomical revisions that affect the scoring of characters commonly used in phylogenetic analyses of early tetrapods. The palate of H. longicostatum is re-interpreted and suggested to be more similar to that of M. pelikani, especially in the nature of the contact between the pterygoids. Both taxa possess lateral lines, and M. pelikani additionally exhibits branchial plates. However, early and rapid ossification of the postcranial skeleton, including a well-developed pubis and ossified epipodials, suggests that neither taxon metamorphosed nor were they neotenic in the sense of branchiosaurids and salamanders. Morphogenetic patterns in the foot suggest that digit 5 was developmentally delayed and the final digit to ossify in M. pelikani and H. longicostatum. Overall patterns of postcranial ossification may indicate postaxial dominance in limb and digit formation, but also more developmental variation in early tetrapods than has been appreciated. The phylogenetic position and developmental patterns of M. pelikani and H. longicostatum are congruent with the hypothesis that early tetrapods lacked metamorphosis ancestrally and that stem-amniotes exhibited derived features of development, such as rapid and complete ossification of the skeleton, potentially prior to the evolution of the amniotic egg. PMID:26083733

Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

PubMed

Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

2016-01-01

Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

Facial bone fragmentation in blind cavefish arises through two unusual ossification processes.

PubMed

Powers, Amanda K; Kaplan, Shane A; Boggs, Tyler E; Gross, Joshua B

2018-05-03

The precise mechanisms underlying cranial bone development, evolution and patterning remain incompletely characterised. This poses a challenge to understanding the etiologies of craniofacial malformations evolving in nature. Capitalising on natural variation, "evolutionary model systems" provide unique opportunities to identify underlying causes of aberrant phenotypes as a complement to studies in traditional systems. Mexican blind cavefish are a prime evolutionary model for cranial disorders since they frequently exhibit extreme alterations to the skull and lateral asymmetries. These aberrations occur in stark contrast to the normal cranial architectures of closely related surface-dwelling fish, providing a powerful comparative paradigm for understanding cranial bone formation. Using a longitudinal and in vivo analytical approach, we discovered two unusual ossification processes in cavefish that underlie the development of 'fragmented' and asymmetric cranial bones. The first mechanism involves the sporadic appearance of independent bony elements that fail to fuse together later in development. The second mechanism involves the "carving" of channels in the mature bone, a novel form of post-ossification remodeling. In the extreme cave environment, these novel mechanisms may have evolved to augment sensory input, and may indirectly result in a trade-off between sensory expansion and cranial bone development.

Forensic age estimation on digital X-ray images: Medial epiphyses of the clavicle and first rib ossification in relation to chronological age.

PubMed

Garamendi, Pedro M; Landa, Maria I; Botella, Miguel C; Alemán, Inmaculada

2011-01-01

In recent years, there has been a renewed interest in forensic sciences about forensic age estimation in living subjects by means of radiological methods. This research was conducted on digital thorax X-rays to test the usefulness of some radiological changes in the clavicle and first rib. The sample consisted in a total of 123 subjects of Spanish origin (61 men and 62 women; age range: 5-75 years). From all subjects, a thorax posterior-anterior radiograph was obtained in digital format. Scoring for fusion of medial epiphyses of the clavicle was carried out by Schmeling's system and ossification of the costal cartilage of the first rib by Michelson's system. Degree of ossification and epiphyseal fusion were analyzed in relation with known age and sex of these subjects. The results give a minimum age of >20 years for full fusion of the medial epiphysis of the clavicle (Stages 4 and 5). Concerning the first rib, all subjects with the final Stage 3 of ossification were above 25 years of age. These results suggest that the first rib ossification might become an additional method to the ones so far recommended for forensic age estimation in subjects around 21. New research would be desirable to confirm this suggestion. © 2010 American Academy of Forensic Sciences.

Dobrogeria aegyssensis, a new early Spathian (Early Triassic) coelacanth from North Dobrogea (Romania)

NASA Astrophysics Data System (ADS)

Cavin, Lionel; Grădinaru, Eugen

2014-06-01

The Early Triassic witnessed the highest taxic diversity of coelacanths (or Actinistia), a clade with a single living genus today. This peak of diversity is accentuated here with the description of a new coelacanth discovered in the lower Spathian (Upper Olenekian, Lower Triassic) cropping out in the Tulcea Veche (Old Tulcea) promontory, in the city of Tulcea, in North Dobrogea, Romania. The bone remains were preserved in a block of limestone, which was chemically dissolved. The resulting 3D and matrix-free ossifications correspond mostly to elements of the skull and branchial apparatus. Posterior parietals, postparietal with associated prootic and basisphenoid allow a precise description of the neurocranium. Ossifications of the lower jaw, together with branchial and pectoral elements, complete the description of this coelacanth and support the coining of a new generic and specific name, Dobrogeria aegyssensis. A phylogenetic analysis of actinistians with the new species recovers clades which were found in most recent analyses, i.e. the Sasseniidae, the Laugiidae, the Coelacanthiformes, the Latimerioidei, the Mawsoniidae and the Latimeriidae, and identifies the new taxon as a non-latimerioid coelacanthiform.

GLI1+ progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue.

PubMed

Dörner, Julia; Martinez Rodriguez, Verena; Ziegler, Ricarda; Röhrig, Theresa; Cochran, Rebecca S; Götz, Ronni M; Levin, Mark D; Pihlajoki, Marjut; Heikinheimo, Markku; Wilson, David B

2017-02-05

As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1 + progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Gli1-creER T2 ) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1 + cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1 + progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1 + progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Amhr2, Foxl2) in response to GDX. These findings support the premise that GLI1 + progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of shape and dispersion media of titanium dioxide nanostructures on microvessel network and ossification.

PubMed

Freyre-Fonseca, Verónica; Medina-Reyes, Estefany I; Téllez-Medina, Darío I; Paniagua-Contreras, Gloria L; Monroy-Pérez, Eric; Vaca-Paniagua, Felipe; Delgado-Buenrostro, Norma L; Flores-Flores, José O; López-Villegas, Edgar O; Gutiérrez-López, Gustavo F; Chirino, Yolanda I

2018-02-01

Titanium dioxide nanoparticles (TiO 2 NPs) production has been used for pigment, food and cosmetic industry and more recently, shaped as belts for treatment of contaminated water, self-cleaning windows and biomedical applications. However, the toxicological data have demonstrated that TiO 2 NPs inhalation induce inflammation in in vivo models and in vitro exposure leads to cytotoxicity and DNA damage. Dermal exposure has limited adverse effects and the possible risks for implants used for tissue regeneration is still under research. Then, it has been difficult to establish a straight statement about TiO 2 NPs toxicity since route of exposure and shapes of nanoparticles play an important role in the effects. In this study we aimed to investigate the effect of three different types of TiO 2 NPs (industrial, food-grade and belts) dispersed in fetal bovine serum (FBS) and saline solution (SS) on microvessel network, angiogenesis gene expression and femur ossification using a chick embryo model after an acute exposure of NPs on the day 7 after eggs fertilization. Microvascular density of chorioallantoic membrane (CAM) was analyzed after 7days of NPs injection and vehicles induced biological effects per se. NPs dispersed in FBS or SS have slight differences in microvascular density, mainly opposite effect on angiogenesis gene expression and no effects on femur ossification for NPs dispersed in SS. Interestingly, NPs shaped as belts dramatically prevented the alterations in ossification induced by FBS used as vehicle. Copyright © 2017 Elsevier B.V. All rights reserved.

Acupuncture at heterotopic acupoints enhances jejunal motility in constipated and diarrheic rats

PubMed Central

Qin, Qing-Guang; Gao, Xin-Yan; Liu, Kun; Yu, Xiao-Chun; Li, Liang; Wang, Hai-Ping; Zhu, Bing

2014-01-01

AIM: To investigate the effect and mechanism of acupuncture at heterotopic acupoints on jejunal motility, particularly in pathological conditions. METHODS: Jejunal motility was assessed using a manometric balloon placed in the jejunum approximately 18-20 cm downstream from the pylorus and filled with approximately 0.1 mL warm water in anesthetized normal rats or rats with diarrhea or constipation. The heterotopic acupoints including LI11 (Quchi), ST37 (Shangjuxu), BL25 (Dachangshu), and the homotopic acupoint ST25 (Tianshu), and were stimulated for 60 s by rotating acupuncture needles right and left at a frequency of 2 Hz. To determine the type of afferent fibers mediating the regulation of jejunal motility by manual acupuncture, the ipsilateral sciatic A or C fibers of ST37 were inactivated by local application of the A-fiber selective demyelination agent cobra venom or the C fiber blocker capsaicin. Methoctramine, a selective M2 receptor antagonist, was injected intravenously to identify a specific role for M2 receptors in mediating the effect of acupuncture on jejunal motility. RESULTS: Acupuncture at heterotopic acupoints, such as LI11 and ST37, increased jejunal motility not only in normal rats, but also in rats with constipation or diarrhea. In normal rats, manual acupuncture at LI11 or ST37 enhanced jejunal pressure from 7.34 ± 0.19 cmH2O to 7.93 ± 0.20 cmH2O, an increase of 9.05% ± 0.82% (P < 0.05), and from 6.95 ± 0.14 cmH2O to 8.97 ± 0.22 cmH2O, a significant increase of 27.44% ± 1.96% (P < 0.01), respectively. In constipated rats, manual acupuncture at LI11 or ST37 increased intrajejunal pressure from 8.17 ± 0.31 cmH2O to 9.86 ± 0.36 cmH2O, an increase of 20.69% ± 2.10% (P < 0.05), and from 8.82 ± 0.28 cmH2O to 10.83 ± 0.28 cmH2O, an increase of 22.81% ± 1.46% (P < 0.05), respectively. In rats with diarrhea, MA at LI11 or ST37 increased intrajejunal pressure from 11.95 ± 0.35 cmH2O to 13.96 ± 0.39 cmH2O, an increase of 16.82% ± 2.35% (P

Myocutaneous sternocleidomastoid flap for reconstruction after the resection of a parapharyngeal heterotopic glioma in a child with cleft palate, and systematic review of parapharyngeal glial heterotopia.

PubMed

Prado-Calleros, Héctor M; Arrieta-Gómez, José R; Castillo-Ventura, Beatriz; Martínez, Sara Parraguirre; Jiménez-Gutiérrez, Carlos; Jiménez-Escobar, Irma

2016-02-01

We describe the surgery and reconstruction employed with a sternocleidomastoid myocutaneous flap for the treatment of a heterotopic glioma in a 2-year-old boy with incomplete palatal fissure who presented with dysphagia and snoring, in whom a lateral pharyngeal wall mass obstructing 60% of the airway was noted. Heterotopic gliomas are uncommonly reported in the parapharyngeal space and should be included in the differential diagnosis at this location in children. Parapharyngeal tumors present difficult diagnostic and management challenges; head and neck surgeons must be prepared not only for the resection but also for the reconstruction of these rare lesions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A new computed tomography method to identify meningitis-related cochlear ossification and fibrosis before cochlear implantation.

PubMed

Ichikawa, Kazunori; Kashio, Akinori; Mori, Harushi; Ochi, Atushi; Karino, Shotaro; Sakamoto, Takashi; Kakigi, Akinobu; Yamasoba, Tatsuya

2014-04-01

To develop a new method to determine the presence of intracochlear ossification and/or fibrosis in cochlear implantation candidates with bilateral profound deafness following meningitis. Diagnostic test assessment. A university hospital. This study involved 15 ears from 13 patients with profound deafness following meningitis who underwent cochlear implantation. These ears showed normal structures, soft tissue, partial bony occlusion, and complete bony occlusion in 4, 3, 2, and 6 ears, respectively. We measured radiodensity in Hounsfield units (HU) using 0.5-mm-thick axial high-resolution computed tomography image slices at 3 different levels in the basal turn, the fenestration, and inferior and ascending segment sites, located along the electrode-insertion path. Pixel-level analysis on the DICOM viewer yielded actual computed tomography values of intracochlear soft tissues by eliminating the partial volume effect. The values were compared with the intraoperative findings. Values for ossification (n = 12) ranged from +547 HU to +1137 HU; for fibrosis (n = 11), from +154 HU to +574 HU; and for fluid (n = 22), from -49 HU to +255 HU. From these values, we developed 2 presets of window width (WW) and window level (WL): (1) WW: 1800, WL: 1100 (200 HU to 2000 HU) and (2) WW: 1500, WL: 1250 (500 HU to 2000 HU). The results using these 2 presets corresponded well to the intraoperative findings. Our new method is easy and feasible for preoperative determination of the presence of cochlear ossification and/or fibrosis that develops following meningitis.

Foxp1/2/4 regulate endochondral ossification as a suppresser complex

PubMed Central

Zhao, Haixia; Zhou, Wenrong; Yao, Zhengju; Wan, Yong; Cao, Jingjing; Zhang, Lingling; Zhao, Jianzhi; Li, Hanjun; Zhou, Rujiang; Li, Baojie; Wei, Gang; Zhang, Zhenlin; French, Catherine A.; Dekker, Joseph D.; Yang, Yingzi; Fisher, Simon E.; lucker, Haley O.; Guo, Xizhi

2015-01-01

Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification. Mice carrying loss-of-function and gain-of-function Foxp mutations had gross defects in appendicular skeleton formation. At the cellular level, over-expression of Foxp1/2/4 in chondroctyes abrogated osteoblast formation and chondrocyte hypertrophy. Conversely, single or compound deficiency of Foxp1/2/4 in skeletal progenitors or chondrocytes resulted in premature osteoblast differentiation in the perichondrium, coupled with impaired proliferation, survival, and hypertrophy of chondrocytes in the growth plate. Foxp1/2/4 and Runx2 proteins interacted in vitro and in vivo, and Foxp1/2/4 repressed Runx2 transactivation function in heterologous cells. This study establishes Foxp1/2/4 proteins as coordinators of osteogenesis and chondrocyte hypertrophy in developing long bones and suggests that a novel transcriptional repressor network involving Foxp1/2/4 may regulate Runx2 during endochondral ossification. PMID:25527076

Degenerative changes and cell death in long-living homo- and heterotopic transplants from embryonic germ layers of rat neocortex.

PubMed

Petrova, E S; Otellin, V A

2003-09-01

Morphological study of allotransplants of rat embryonic neocortex 14-18 months after transplantation into the neocortex, lateral cerebral ventricle, and sciatic nerve of adult animals revealed death of nerve and glial cells in the delayed postoperation period independently on the site of transplantation. After heterotopic transplantation the count of degenerated neurons was 2 times higher that after homotopic transplantation. In heterotopic transplants a considerable number of grafted neurons underwent reversible and irreversible degenerative changes accompanied by their premature aging. Neuronal death is probably determined by insufficiency of trophic influence from afferent structures and target tissues. We hypothesized that antiapoptotic preparations can be used for prevention of transplanted cell death. It was also found that degeneration of neurons was associated with impaired vascularization of transplants and pronounced immune reaction of the recipient in late posttransplantation period. Transplantation of embryonic brain structures can serve as a model system in studies concerning involutive and pathological processes in the central nervous system and in the search for factors improving survival of neurons.

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification.

PubMed

Osinga, Rik; Di Maggio, Nunzia; Todorov, Atanas; Allafi, Nima; Barbero, Andrea; Laurent, Frédéric; Schaefer, Dirk Johannes; Martin, Ivan; Scherberich, Arnaud

2016-08-01

: Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. Unlike bone marrow-derived stromal cells (also known as bone marrow-derived mesenchymal stromal/stem cells), adipose-derived stromal cells (ASC) have so far failed to form a bone organ by ECO. The goal of the present study was to assess whether priming human ASC to a defined stage of chondrogenesis in vitro allows their autonomous ECO upon ectopic implantation. ASC were cultured either as micromass pellets or into collagen sponges in chondrogenic medium containing transforming growth factor-β3 and bone morphogenetic protein-6 for 4 weeks (early hypertrophic templates) or for two additional weeks in medium supplemented with β-glycerophosphate, l-thyroxin, and interleukin1-β to induce hypertrophic maturation (late hypertrophic templates). Constructs were implanted in vivo and analyzed after 8 weeks. In vitro, ASC deposited cartilaginous matrix positive for glycosaminoglycans, type II collagen, and Indian hedgehog. Hypertrophic maturation induced upregulation of type X collagen, bone sialoprotein, and matrix metalloproteinase13 (MMP13). In vivo, both early and late hypertrophic templates underwent cartilage remodeling, as assessed by MMP13- and tartrate-resistant acid phosphatase-positive staining, and developed bone ossicles, including bone marrow elements, although to variable degrees of efficiency. In situ hybridization for human-specific sequences and staining with a human specific anti-CD146 antibody demonstrated the direct contribution of ASC to bone and stromal tissue formation. In conclusion, despite their debated skeletal progenitor nature, human ASC can generate bone organs through ECO when suitably primed in vitro. Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow

Morphometric study of the two fused primary ossification centers of the clavicle in the human fetus.

PubMed

Baumgart, Mariusz; Wiśniewski, Marcin; Grzonkowska, Magdalena; Badura, Mateusz; Dombek, Małgorzata; Małkowski, Bogdan; Szpinda, Michał

2016-10-01

A satisfactory understanding of the clavicle development may be contributing to both the diagnosis of its congenital defects and prevention of perinatal damage to the shoulder girdle. This study was carried out to examine the transverse and sagittal diameters, cross-sectional area and volume of the two fused primary ossification centers of the clavicle. Using the methods of CT, digital-image analysis and statistics, the size for two fused primary ossification centers of the clavicle in 42 spontaneously aborted human fetuses at ages of 18-30 weeks was studied. Without any male-female and right-left significant differences, the best fit growth models for two fused primary ossification centers of the clavicle were as follows: y = -31.373 + 15.243 × ln(age) ± 1.424 (R (2) = 0.74) for transverse diameter, y = -7.945 + 3.225 × ln(age) ± 0.262 (R (2) = 0.78), y = -4.503 + 2.007 × ln(age) ± 0.218 (R (2) = 0.68), and y = -4.860 + 2.117 × ln(age) ± 0.200 (R (2) = 0.73) for sagittal diameters of the lateral, middle and medial ends respectively, y = -31.390 + 2.432 × age ± 4.599 (R (2) = 0.78) for cross-sectional area, and y = 28.161 + 0.00017 × (age)(4) ± 15.357 (R (2) = 0.83) for volume. With no sex and laterality differences, the fused primary ossification centers of the clavicle grow logarithmically in both transverse and sagittal diameters, linearly in cross-sectional area, and fourth-degree polynomially in volume. Our normative quantitative findings may be conducive in monitoring normal fetal growth and screening for inherited faults and anomalies of the clavicle in European human fetuses.

Ossifying tendinitis of the rotator cuff after arthroscopic excision of calcium deposits: report of two cases and literature review.

PubMed

Merolla, Giovanni; Dave, Arpit C; Paladini, Paolo; Campi, Fabrizio; Porcellini, Giuseppe

2015-03-01

Ossifying tendinitis (OT) is a type of heterotopic ossification, characterized by deposition of hydroxyapatite crystals in a histologic pattern of mature lamellar bone. It is usually associated with surgical intervention or trauma and is more commonly seen in Achilles or distal biceps tendons, and also in the gluteus maximus tendon. To our knowledge, there is no description of OT as a complication of calcifying tendinitis of the rotator cuff. In this report, we describe two cases in which the patients developed an OT of the supraspinatus after arthroscopic removal of calcium deposits. The related literature is reviewed.

What you need to know about ossification of the posterior longitudinal ligament to optimize cervical spine surgery: A review

PubMed Central

Epstein, Nancy E.

2014-01-01

What are the risks, benefits, alternatives, and pitfalls for operating on cervical ossification of the posterior longitudinal ligament (OPLL)? To successfully diagnose OPLL, it is important to obtain Magnetic Resonance Images (MR). These studies, particularly the T2 weighted images, provide the best soft-tissue documentation of cord/root compression and intrinsic cord abnormalities (e.g. edema vs. myelomalacia) on sagittal, axial, and coronal views. Obtaining Computed Tomographic (CT) scans is also critical as they best demonstrate early OPLL, or hypertrophied posterior longitudinal ligament (HPLL: hypo-isodense with punctate ossification) or classic (frankly ossified) OPLL (hyperdense). Furthermore, CT scans reveal the “single layer” and “double layer” signs indicative of OPLL penetrating the dura. Documenting the full extent of OPLL with both MR and CT dictates whether anterior, posterior, or circumferential surgery is warranted. An adequate cervical lordosis allows for posterior cervical approaches (e.g. lamionplasty, laminectomy/fusion), which may facilitate addressing multiple levels while avoiding the risks of anterior procedures. However, without lordosis and with significant kyphosis, anterior surgery may be indicated. Rarely, this requires single/multilevel anterior cervical diskectomy/fusion (ACDF), as this approach typically fails to address retrovertebral OPLL; single or multilevel corpectomies are usually warranted. In short, successful OPLL surgery relies on careful patient selection (e.g. assess comorbidities), accurate MR/CT documentation of OPLL, and limiting the pros, cons, and complications of these complex procedures by choosing the optimal surgical approach. Performing OPLL surgery requires stringent anesthetic (awake intubation/positioning) and also the following intraoperative monitoring protocols: Somatosensory evoked potentials (SSEP), motor evoked potentials (MEP), and electromyography (EMG). PMID:24843819

Diagnosis and treatment of infraspinatus tendon-bursa ossification in a Eurasian Dog.

PubMed

Ungru, Julia; Hungerbühler, Stephan; Henninger, Wolfgang; Klupiec, Petra; Bödeker, Julia; Langer, Anna; Fehr, Michael; Harms, Oliver

2018-04-01

A 4-year-old male Eurasian Dog presented at our veterinary clinic with a history of perpetual forelimb lameness in both thoracic limbs. In the clinical exploration, direct pressure over the infraspinatus tendon of insertion caused pain in both thoracic forelimbs and a firm band-like structure was palpable. No improvement was observed after treatment with rest, non-steroidal anti-inflammatory drugs and an intralesional injection of a long-acting glucocorticoid. Radiographic examination, ultrasonographic exploration and computed tomography were performed, identifying ossified structures lateral to the proximal humerus and an irregular roughened periosteum at the insertion and tendon of the infraspinatus muscle on both sides. There were more distinct alterations on the right thoracic limb. The imaging results led to a diagnosis of an infraspinatus tendon-bursa ossification accompanied by a chronic tendinopathy/tendovaginitis, accentuated on the right side. The dog was subjected to physiotherapy and autologous conditioned plasma (ACP) was injected into the insertion of the infraspinatus muscle of both thoracic limbs. After 5 months of physiotherapy and two injections of ACP with an interval of one week in both forelimbs, the dog showed no signs of lameness. This case report describes the diagnosis and management of infraspinatus tendon-bursa ossification in a Eurasian Dog. To the authors' knowledge, this condition has previously not been described in this breed of dog. Schattauer GmbH.

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model

PubMed Central

Salga, Marjorie; Begot, Laurent; Holy, Xavier; Chedik, Malha; de l’Escalopier, Nicolas; Torossian, Fréderic; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline; Genêt, François

2017-01-01

We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis. PMID:28854256

Establishing the Mineral Apposition Rate of Heterotopic Ossification for Prevention of Recurrence

DTIC Science & Technology

2015-12-01

oxygenation has been demonstrated to have deleterious effects on wound closure rates, latency to resumption of an unperturbed blood flow, and may delay the...techniques like near-infrared spectroscopy and blood oxygen level-dependent magnetic resonance imaging may provide noninvasive, precise, and time- effective ...Itada N, Friedenberg ZB. Cathodic oxygen consumption and electrically induced osteogenesis. Clin Orthop Relat Res. 1975;(107):277–282. 27. Ren H

Arthroscopic excision of heterotopic calcification in a chronic rectus femoris origin injury: a case report

PubMed Central

El-Husseiny, M; Sukeik, M; Haddad, FS

2012-01-01

Rectus femoris origin injuries in adult athletes are uncommon. In the acute phase, conservative treatment seems to have a favourable outcome, with surgical repair reserved for unsuccessful cases only. However, a group of patients may develop chronic pain and disability after recovery from the acute phase due to heterotopic calcification occurring at the site of injury. Open and arthroscopic excision of such calcifications has been described in the literature although arthroscopic excision of large calcified lesions in the rectus femoris has not been reported previously. A relevant case is presented and discussed. PMID:22507710

Distinct requirements of wls, wnt9a, wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification

PubMed Central

Ling, Irving TC; Rochard, Lucie; Liao, Eric C.

2017-01-01

Formation of the mandible requires progressive morphologic change, proliferation, differentiation and organization of chondrocytes preceding osteogenesis. The Wnt signaling pathway is involved in regulating bone development and maintenance. Chondrocytes that are fated to become bone require Wnt to polarize and orientate appropriately to initiate the endochondral ossification program. Although the canonical Wnt signaling has been well studied in the context of bone development, the effects of non-canonical Wnt signaling in regulating the timing of cartilage maturation and subsequent bone formation in shaping ventral craniofacial structure is not fully understood.. Here we examined the role of the non-canonical Wnt signaling pathway (wls, gpc4, wnt5b and wnt9a) in regulating zebrafish Meckel’s cartilage maturation to the onset of osteogenic differentiation. We found that disruption of wls resulted in a significant loss of craniofacial bone, whereas lack of gpc4, wnt5b and wnt9a resulted in severely delayed endochondral ossification. This study demonstrates the importance of the non-canonical Wnt pathway in regulating coordinated ventral cartilage morphogenesis and ossification. PMID:27908786

Hatching, growth, ion accumulation, and skeletal ossification of brook trout (Salvelinus fontinalis) alevins in acidic soft waters

USGS Publications Warehouse

Steingraeber, M.T.; Gingerich, W.H.

1991-01-01

Brook trout eyed eggs and subsequent alevins were exposed to pH 5.0, 6.5, and 7.0 in soft reconstituted water and to pH 8.2 in hard well water for up to 72 d. Hatching was delayed and hatching success reduced (p K+ > Cl- during yolk absorption and early exogenous feeding. Whole-body monovalent ion concentrations were reduced for short periods during yolk absorption in alevins exposed to pH 6.5 and throughout most of the experiment for those exposed to pH 5.0. Whole-body Mg2+ concentrations were not affected by treatment pH and remained near their median hatch level throughout the exposure. The whole-body concentration of Ca2+ was reduced in fish exposed to pH 5.0, particularly near the end of the experiment. Calcium accumulation in fish was influenced by the interaction of pH and time at pH 5.0 but not at the other pH levels. Alevins exposed to pH 5.0 experienced delayed ossification of skeletal structures associated with feeding, respiration, and locomotion that usually persisted for up to 10 d. The detection of skeletal abnormalities early in life might aid in identifying fish populations at risk in acidified waters.

Magnetic resonance imaging detection of early experimental periostitis. Comparison of magnetic resonance imaging, computed tomography, and plain radiography with histopathologic correlation.

PubMed

Spaeth, H J; Chandnani, V P; Beltran, J; Lucas, J G; Ortiz, I; King, M A; Bennett, W F; Bova, J G; Mueller, C F; Shaffer, P B

1991-04-01

This study characterizes the appearance of periosteal reaction by magnetic resonance imaging (MRI), and evaluates the efficacy of MRI versus computed tomography (CT), and plain film radiography (PF) in detecting early, experimentally induced periostitis. Acute Staphylococcus aureus osteomyelitis was induced in 30 legs of 20 New Zealand white rabbits. The rabbits were then imaged with MR, contrast-unenhanced CT, and PF 4 days after infection. Histologically, periosteal elevation was present in 27 cases. Periosteal ossification was seen in 23 cases, and cellular reaction without ossification in 4 cases. Periosteal reaction was demonstrated by PF in 21 (78%) and by CT in 20 (74%) cases. Evidence of periostitis was seen by MR in all 27% (100%) cases. MR resulted in two false-positive diagnoses. Multiple concentric, alternating high and low signal arcs demonstrated by MR in 19 (70%) cases represented periosteal ossification surrounded by fibrous or granulation tissue. These findings demonstrate the ability of MR to detect periostitis despite the absence of periosteal ossification. MR was more sensitive than CT (P less than .05) or PF (P less than .05) in the detection of experimentally induced periostitis.

Chronic cystitis with ossification of the bladder wall in a 6-month-old German shepherd dog

PubMed Central

Zotti, Alessandro; Fant, Pierluigi; De Zan, Gabrita; Mollo, Antonio; Busetto, Roberto

2007-01-01

Ossification of the bladder wall, detected radiographically as a nonhomogeneous radiopaque area in the cranioventral part of the bladder in a puppy, is reported. We speculate that chronic inflammation due to the presence of uroliths in the lumen may have stimulated a metaplastic transformation of the cells. PMID:17966335

Genetic analysis of ossification of the posterior longitudinal ligament.

PubMed

Matsunaga, S; Yamaguchi, M; Hayashi, K; Sakou, T

1999-05-15

The human leukocyte antigen (HLA) haplotypes in families of patients with known ossification of the posterior longitudinal ligament (OPLL) were reviewed. To clarify how genetic factors relate to the development of OPLL. The association between genetic factors and the development of OPLL is still unknown. The association between HLA haplotypes and OPLL was studied in families of 24 patients with OPLL. The prevalence of OPLL was higher in the siblings showing a higher share of identical HLA haplotypes: 10 (53%) of 19 with concurrence of two strands, and 5 (24%) of 21 with concurrence of one strand. Of 21 subjects who had no HLA haplotype identical with that in OPLL patients, only one showed evidence of OPLL. Genetic factors predispose toward the development of OPLL.

Application of human induced pluripotent stem cells to model fibrodysplasia ossificans progressiva.

PubMed

Barruet, Emilie; Hsiao, Edward C

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients have mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Since it is often difficult or impossible to obtain large amounts of tissue from human donors due to the risks of inciting more heterotopic bone formation, human induced pluripotent stem cells (hiPSCs) provide an attractive source for establishing in vitro disease models and for applications in drug screening. hiPSCs have the ability to self-renew, allowing researchers to obtain large amounts of starting material. hiPSCs also have the potential to differentiate into any cell type in the body. In this review, we discuss how the application of hiPSC technology to studying FOP has changed our perspectives on FOP disease pathogenesis. We also consider ongoing challenges and emerging opportunities for the use of human iPSCs in drug discovery and regenerative medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Heterotopic expression of MPF2 is the key to the evolution of the Chinese lantern of Physalis, a morphological novelty in Solanaceae

PubMed Central

He, Chaoying; Saedler, Heinz

2005-01-01

Morphological novelties arise through changes in development, but the underlying causes of such changes are largely unknown. In the genus Physalis, sepals resume growth after pollination to encapsulate the mature fruit, forming the “Chinese lantern,” a trait also termed inflated-calyx syndrome (ICS). STMADS16, which encodes a MADS-box transcription factor, is expressed only in vegetative tissues in Solanum tuberosum. Its ortholog in Physalis pubescens, MPF2, is expressed in floral tissues. Knockdown of MPF2 function in Physalis by RNA interference (RNAi) reveals that MPF2 function is essential for the development of the ICS. The phenotypes of transgenic S. tuberosum plants that overexpress MPF2 or STMADS16 corroborate these findings: these plants display enlarged sepals. Although heterotopic expression of MPF2 is crucial for ICS, remarkably, fertilization is also required. Although the ICS is less prominent or absent in the knockdown transgenic plants, epidermal cells are larger, suggesting that MPF2 exerts its function by inhibiting cell elongation and promoting cell division. In addition, severely affected Physalis knockdown lines are male sterile. Thus, heterotopic expression of MPF2 in floral tissues is involved in two novel traits: expression of the ICS and control of male fertility. Sequence differences between the promoter regions of the MPF2 and STMADS16 genes perhaps reflect exposure to different selection pressures during evolution, and correlate with the observed differences in their expression patterns. In any case, the effects of heterotopic expression of MPF2 underline the importance of recruitment of preexisting transcription factors in the evolution of novel floral traits. PMID:15824316

A hypothesis on the formation of the primary ossification centers in the membranous neurocranium: a mathematical and computational model.

PubMed

Garzón-Alvarado, Diego A

2013-01-21

This article develops a model of the appearance and location of the primary centers of ossification in the calvaria. The model uses a system of reaction-diffusion equations of two molecules (BMP and Noggin) whose behavior is of type activator-substrate and its solution produces Turing patterns, which represents the primary ossification centers. Additionally, the model includes the level of cell maturation as a function of the location of mesenchymal cells. Thus the mature cells can become osteoblasts due to the action of BMP2. Therefore, with this model, we can have two frontal primary centers, two parietal, and one, two or more occipital centers. The location of these centers in the simplified computational model is highly consistent with those centers found at an embryonic level. Copyright © 2012 Elsevier Ltd. All rights reserved.

Trauma-induced myelopathy in patients with ossification of the posterior longitudinal ligament.

PubMed

Matsunaga, Shunji; Sakou, Takashi; Hayashi, Kyoji; Ishidou, Yasuhiro; Hirotsu, Masataka; Komiya, Setsuro

2002-09-01

In these prospective and retrospective studies the authors evaluated trauma-induced myelopathy in patients with ossification of the posterior longitudinal ligament (OPLL) to determine the effectiveness of preventive surgery for this disease. The authors studied 552 patients with cervical OPLL, including 184 with myelopathy at the time of initial consultation and 368 patients without myelopathy at that time. In the former group of 184 patients retrospective analysis was performed using an interview survey to ascertain the relationship between onset of myelopathy and trauma. In the latter group of 368 patients prospective examination was conducted by assessing radiographic findings and noting changes in clinical symptoms apparent during regular physical examination. The follow-up period ranged from 10 to 32 years (mean 19.6 years). In the retrospective investigation, 24 patients (13%) identified cervical trauma as the trigger of their myelopathy. In the prospective investigation, 70% of patients did not develop myelopathy over a follow-up period greater than 20 years (determined using the Kaplan-Meier method). Of the 368 patients without myelopathy at the time of initial consultation, only six patients (2%) subsequently developed trauma-induced myelopathy. Types of ossification in patients who developed trauma-induced myelopathy were primarily a mixed type. All patients in whom stenosis affected 60% or greater of the spinal canal developed myelopathy regardless of a history of trauma. Preventive surgery prior to onset of myelopathy is unnecessary in most patients with OPLL.

Revascularization of the graft in obliterative bronchiolitis after heterotopic tracheal transplantation.

PubMed

Nemska, Simona; Daubeuf, François; Frossard, Nelly

2016-02-01

Obliterative bronchiolitis is the principal long-term problem for lung transplant patients. One of the simplest and most reproducible animal models of obliterative bronchiolitis is heterotopic tracheal transplantation in subcutaneous tissue, where the graft is not primarily vascularized. We demonstrate here the rapid graft revascularization and the kinetics of expression of its angiogenic and lymphatic factors. We performed iso- and allotracheal transplantations harvested on day 0-21. The number of functional blood vessels, quantified after intravenous biotinylated dextran administration, increased from D0 (0 for both iso- and allografts) to D21 (44 ± 8 vessels/mm(2) in isografts and 22 ± 3 in allografts, P < 0.001 for both vs. D0). VEGF mRNA expression assessed by qPCR peaked on D1 (4.3-fold increase in isografts and 4.0-fold in allografts, P < 0.0001 for both vs. D0), but receded thereafter. Angiopoietin-1, involved in the maturation of the neoformed vessels, increased later on, by 6.2-fold (P < 0.05) in isografts and 11.5-fold in allografts (P < 0.001) by D21, and angiopoietin-2 by 7.8-fold in isografts (P < 0.05) and 13.8-fold in allografts (P < 0.01). Although always present in the iso- and allografts, there were significantly more and larger LYVE1(+) lymphatic vessels at D21 in allografts than in isografts. Thus, we demonstrate that tracheal grafts are rapidly revascularized by functional blood and lymphatic vessels, due to early VEGF and subsequent angiopoietins expression, which is a new advantage of this model, in addition to its ease of use, reproducibility, and viability in the absence of immunosuppressive treatment. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway

PubMed Central

Matsushita, Takehiko; Wilcox, William R.; Chan, Yuk Yu; Kawanami, Aya; Bükülmez, Hülya; Balmes, Gener; Krejci, Pavel; Mekikian, Pertchoui B.; Otani, Kazuyuki; Yamaura, Isakichi; Warman, Matthew L.; Givol, David; Murakami, Shunichi

2009-01-01

Activating mutations in FGFR3 cause achondroplasia and thanatophoric dysplasia, the most common human skeletal dysplasias. In these disorders, spinal canal and foramen magnum stenosis can cause serious neurologic complications. Here, we provide evidence that FGFR3 and MAPK signaling in chondrocytes promote synchondrosis closure and fusion of ossification centers. We observed premature synchondrosis closure in the spine and cranial base in human cases of homozygous achondroplasia and thanatophoric dysplasia as well as in mouse models of achondroplasia. In both species, premature synchondrosis closure was associated with increased bone formation. Chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increases Bmp ligand mRNA expression and decreases Bmp antagonist mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. Spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients, therefore, may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure. PMID:18923003

Ossification of the posterior longitudinal ligament of the cervical spine: etiology and natural history.

PubMed

Matsunaga, Shunji; Sakou, Takashi

2012-03-01

Review article. To review the etiology, natural history, measurement tools, and image diagnosis of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. OPLL is a well-known disease that causes myelopathy. Genetic factors are very important for development of OPLL. However, the pathogenetic gene and natural history of OPLL have not been clarified. The authors reviewed studies about the etiology, natural history, measurement tools, and diagnosis of OPLL, which had been performed by the members of the Investigation Committee on the Ossification of the Spinal Ligaments of the Japanese Ministry of Health, Labour, and Welfare. The prevalence of OPLL in the general Japanese population was reported to be 1.9% to 4.3% among people older than 30 years. Genetic factors are important for development of OPLL, and some candidate genes have been reported. Clinical course of OPLL has been clarified by a prospective long-term follow-up study. Some radiographic predictors for development of myelopathy were introduced. Image diagnosis of OPLL is easy by plain radiographs, but magnetic resonance imaging and computed tomography are useful to determine cord compression by OPLL. OPLL should be managed on the basis of the consideration of its natural history. Elucidation of pathogenetic genes of OPLL will introduce a new approach for management of OPLL.

Posterior hip dislocation in a non-professional football player: a case report and review of the literature.

PubMed

Bakalakos, Matthaios; Benetos, Ioannis S; Rozis, Meletios; Vlamis, John; Pneumaticos, Spiros

2018-06-02

The majority of injuries during a football game are contusions, sprains and/or strains in the thigh, knee and ankle. Hip dislocations account for 2-5% of total hip dislocations, and they can be posterior or anterior. Major complications of traumatic hip dislocation include avascular necrosis of femoral head, secondary osteoarthritis, sciatic nerve injury and heterotopic ossification. On the occasion of a case of a 33-year-old football player, who suffered a posterior hip dislocation, associated with a posterior wall fracture of the acetabulum, while playing football, we review the literature and analyze the various mechanisms of injury, the possible complications and the management including surgery and rehabilitation.

Mid- to long-term outcomes of posterior decompression with instrumented fusion for thoracic ossification of the posterior longitudinal ligament.

PubMed

Koda, Masao; Furuya, Takeo; Okawa, Akihiko; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Aramomi, Masaaki; Ikeda, Osamu; Mannoji, Chikato

2016-05-01

Posterior decompression with instrumented fusion (PDF) surgery has been previously reported as a relatively safe surgical procedure for any type of thoracic ossification of the longitudinal ligament (OPLL). However, mid- to long-term outcomes are still unclear. The aim of the present study was to elucidate the mid- to long-term clinical outcome of PDF surgery for thoracic OPLL patients. The present study included 20 patients who had undergone PDF for thoracic OPLL and were followed for at least 5years. Increment change and recovery rate of the Japanese Orthopaedic Association (JOA) score were assessed. Revision surgery during the follow-up period was also recorded. Average JOA scores were 3.5 preoperatively and 7.1 at final follow-up. The average improvement in JOA score was 3.8 points and the average recovery rate was 47.0%. The JOA score showed gradual increase after surgery, and took 9months to reach peak recovery. As for neurological complications, two patients suffered postoperative paralysis, but both recovered without intervention. Six revision surgeries in four patients were related to OPLL. Additional anterior thoracic decompression for remaining ossification at the same level of PDF surgery was performed in one patient. Decompression surgery for deterioration of symptoms of pre-existing cervical OPLL was performed in three patients. One patient had undergone lumbar and cervical PDF surgery for de novo ossification foci of the lumbar and cervical spine. PDF surgery for thoracic OPLL is thus considered a relatively safe and stable surgical procedure considering the mid- to long-term outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Notch signaling pathways in human thoracic ossification of the ligamentum flavum.

PubMed

Qu, Xiaochen; Chen, Zhongqiang; Fan, Dongwei; Sun, Chuiguo; Zeng, Yan; Hou, Xiaofei; Ning, Shanglong

2016-08-01

This study investigated the pathological process of Notch signaling in the osteogenesis of ligamentum flavum tissues and cells, and the associated regulatory mechanisms. Notch receptors, ligands, and target genes were identified by quantitative polymerase chain reaction (qPCR) in ligamentum flavum cells and immunohistochemistry in ligamentum flavum sections from ossification of the ligamentum flavum (OLF) patients and controls. The temporospatial expression patterns of JAG1/Notch2/HES1 in human ligamentum flavum cells during osteogenic differentiation were determined by qPCR. Lentiviral vectors for Notch2 overexpression and knockdown were constructed and transfected into ligamentum flavum cells before osteogenic differentiation to examine the function of Notch signaling pathways in the osteogenic differentiation of ligamentum flavum cells. Alkaline phosphatase, Runx2, Osterix, osteocalcin, and osteopontin mRNA levels, alkaline phosphatase activity, and Alizarin Red staining were used as indicators of osteogenic differentiation. JAG1/Notch2/HES1 mRNA levels were up-regulated in ligamentum flavum cells from OLF patients, which increased during osteogenic differentiation. Immunohistochemical analysis suggested positive Notch2 expression at the ossification front. Down-regulation of Notch2 expression decelerated osteogenic differentiation of ligamentum flavum cells, and Notch2 overexpression promoted osteogenic differentiation of ligamentum flavum cells. Expression of Runx2 and Osterix increased in a manner similar to that of Notch2 during osteogenic differentiation of ligamentum flavum cells, and Notch2 knockdown and overexpression influenced their expression levels. Notch signaling plays an important role in OLF, and Notch may affect the osteogenic differentiation of ligamentum flavum cells via interactions with Runx2 and Osterix.© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1481-1491, 2016. © 2016 Orthopaedic Research

Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study.

PubMed

Zhang, Jing; Li, Tingting; Xu, Liangzhi; Li, Wenjuan; Cheng, Meng; Zhuang, Jing; Chen, Yan; Xu, Wenming

2013-08-01

Leptin may be a potential option in preventing osteoporosis for menopausal women. The objective of this study is to explore the molecular mechanism of leptin on bone metabolism in osteoblast. Primary osteoblasts were isolated from parietal bone of adult female rats. mRNA level of OB-Rb in osteoblasts was inhibited by siRNA to block leptin signal transmission. The whole genome expression was tested by using gene chip to preliminarily explore the molecular mechanism of leptin in regulating osteoblast activity. The optimal concentration of siRNA was 25 nM, resulting in a maximal inhibition of OB-Rb mRNA. Ossification (p < 0.05) and bone mineralization (p = 0.0001) were downregulated by inhibiting leptin signal transmission, while bone resorption (p = 0.007), osteoblast differentiation (p = 0.026) and negative regulation of bone remodeling (p = 0.004) were upregulated. The expressions of some genes were regulated by OB-Rb siRNA. The expressions of alkaline phosphatase (p = 0.014) and osteocalcin (p = 0.002) were reduced, while that of vascular endothelial growth factor A (p = 0.0076) and IL-6 (p = 0.021) were increased. In a model of osteoblast, leptin positively promotes ossification through multiple ways including bone mineralization, remodeling, resorption and osteoblast differentiation, but which way plays the most critical role is not discussed in this study and needs to be clarified in future.

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

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

Pan, Zhengqi

Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showedmore » a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. - Highlights: • Glucocorticoid but not ethanol enhanced the expression of OPG in chondrocytes. • PEE reduced osteoclast differentiation relative with over-expression of OPG. • PEE inhibited endochondral ossification in fetal long

Lifetime Fluorescence and Raman Imaging for Detection of Wound Failure and Heterotopic Ossification

DTIC Science & Technology

2015-12-01

containing ten bandpass filters ( Semrock Fluorescence filters) centered at: 407nm, 434 nm, 465 nm, 494 nm, 520 nm, 542 nm, 572 nm, 605 nm, 652 nm, 676 nm...meat (~2 - 3 mm thickness), and a bottom piece (~8 mm). The system was built around an 852 nm tunable narrow-band optical filter ( Semrock , LL01-852...optical filters to block light that falls outside the detection band: 785 nm notch filter ( Semrock , NF03-785E-25), and a bandpass filter at 842 nm

Lifetime Fluorescence and Raman Imaging for Detection of Wound Failure and Heterotopic Ossification

DTIC Science & Technology

2014-10-01

Filter Wheel) containing ten bandpass filters ( Semrock Fluorescence filters) centered at: 407nm, 434 nm, 465 nm, 494 nm, 520 nm, 542 nm, 572 nm...and a bottom piece (~8 mm). The system was built around an 852 nm tunable narrow-band optical filter ( Semrock , LL01-852-25) mounted in front of...light that falls outside the detection band: 785 nm notch filter ( Semrock , NF03-785E-25), and a bandpass filter at 842 nm ( Semrock , FF01-842/56-25

Lifetime Fluorescence and Raman Imaging for Detection of Wound Failure and Heterotopic Ossification

DTIC Science & Technology

2013-10-01

currently working on the project. Publications: [1] W. S. Grundfest and Z. D. Taylor, " Biophotonics at UCLA," in Univeristy of California... Biophotonics Alliance (UCBA), San Franciso, CA, 2012. [2] A. Papour, Z. D. Taylor, W. Yong, M. S. John, O. Stafsudd, and W. S. Grundfest, "Multi-Spectral

Clinical and radiological analysis of Bryan cervical disc arthroplasty: eight-year follow-up results compared with anterior cervical discectomy and fusion.

PubMed

Lei, Tao; Liu, Yaming; Wang, Hui; Xu, Jiaxin; Ma, Qinghua; Wang, Linfeng; Shen, Yong

2016-06-01

Bryan cervical disc arthroplasty has been reported with satisfactory short- and medium-term clinical results. However, the long-term clinical and radiographic outcomes are seldom reported. The purpose of this study was to compare the eight-year follow-up results in patients who underwent Bryan disc arthroplasty with patients received ACDF, and assess the incidence of heterotopic ossification (HO) and its effect on clinical outcome and mobility of the device. Thirty-one patients underwent Bryan disc arthroplasty, and 35 patients underwent ACDF were included in the study. The Japanese Orthopedic Association (JOA) scores, neck disability index (NDI), visual analogue scale (VAS) of neck and arm pain, and the radiographs were used to evaluate the outcomes. The heterotopic ossification (HO) was determined by CT scan and was classified into three subgroups to compare the related effect. Adjacent segment degeneration (ASD) was also observed. At final follow-up, there were no significant differences in JOA scores between two groups, but the improvement in NDI and neck or arm VAS were significantly greater in the Bryan disc cohort. The range of motion at the index level was 7.0° in Bryan group, while 100 % bone fusion were achieved in ACDF group. HO was observed in 18 (51.4 %) levels. There were more restricted movement of the prosthesis and slight higher rate of axial pain in patients with severe-HO (grade III and IV). Fourteen (28.6 %) levels developed ASD in Bryan group, which was significantly lower than that (58.6 %) in ACDF group. At eight year follow-up, the clinical and radiographic outcomes of Bryan cervical disc arthroplasty compared favorably to those of ACDF. It avoided accelerated adjacent segment degeneration by preserving motion. However, severe HO restricted the ROM of the index levels and maybe associated with post-operative axial pain.

Management of acetabular fractures with modified posterior approach to spare external hip rotators.

PubMed

Sarlak, Ahmet Y; Selek, Ozgur; Inanir, Murat; Musaoglu, Resul; Baran, Tuncay

2014-04-01

In the present study the quality of reduction and incidence of complications in hip external rotator sparing modified posterior approach was assessed in both simple and complex acetabular fractures. This retrospective study includes 37 patients (38 hips) with a mean age of 42.1 years (range 21-60), that had been treated for displaced acetabular fractures from June 2007 through May 2011. They were reviewed at a mean of 3 years (20-67 months). The fractures were classified according to the Letournel-Judet classification. Anatomic reduction and stable fixation of the fracture with less than 2mm residual displacement was achieved in 28 of 38 hips. At the final follow up the patients were evaluated clinically according to Merle d'Aubigne and Postel scoring system which had been modified by Matta and radiologically based on the criteria described by Matta. The clinical results were excellent in 20, good in 8, fair in 8, and poor 2 hips. Complications included two superficial local wound infection and 10 heterotopic ossification with 7 of the cases having grade I heterotopic ossification. Avascular necrosis of the femoral head was not seen in any of the 38 hips. One patient with preoperative sciatic nerve palsy had complete recovery of neurologic function. There were no cases of deep vein thrombosis or pulmonary embolism. The functional outcome was satisfactory in most of the cases and comparable with other larger series. Using the limited part of Henry's sciatic nerve exposure skin incision - working in the plane between gluteus maximus and the tensor fascia lata as in the classical Gibson approach and two portal external rotator hip sparing approach resulted in good fracture reduction without approach related complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unusual fan shaped ossification in a female fetus with radiological features of boomerang dysplasia

PubMed Central

Odent, S.; Loget, P.; Le Marec, B.; Delezoide, A.; Maroteaux, P.

1999-01-01

We report on a female fetus of 24 weeks whose clinical and radiological findings were compatible with boomerang dysplasia (BD). However, histopathology was unusual with a lateral fan shaped diaphyseal ossification. This has never been described either in typical atelosteogenesis I (AT-I) or in BD. The purpose of this report is to find out if this condition is a separate lethal bone dysplasia or another histological feature of the nosological group of AT-I and BD. 


Keywords: boomerang dysplasia; atelosteogenesis; lethal chondrodysplasia; lethal dwarfism PMID:10227404

Hidden morphological diversity among early tetrapods.

PubMed

Pardo, Jason D; Szostakiwskyj, Matt; Ahlberg, Per E; Anderson, Jason S

2017-06-29

Phylogenetic analysis of early tetrapod evolution has resulted in a consensus across diverse data sets in which the tetrapod stem group is a relatively homogenous collection of medium- to large-sized animals showing a progressive loss of 'fish' characters as they become increasingly terrestrial, whereas the crown group demonstrates marked morphological diversity and disparity. The oldest fossil attributed to the tetrapod crown group is the highly specialized aïstopod Lethiscus stocki, which shows a small size, extreme axial elongation, loss of limbs, spool-shaped vertebral centra, and a skull with reduced centres of ossification, in common with an otherwise disparate group of small animals known as lepospondyls. Here we use micro-computed tomography of the only known specimen of Lethiscus to provide new information that strongly challenges this consensus. Digital dissection reveals extremely primitive cranial morphology, including a spiracular notch, a large remnant of the notochord within the braincase, an open ventral cranial fissure, an anteriorly restricted parasphenoid element, and Meckelian ossifications. The braincase is elongate and lies atop a dorsally projecting septum of the parasphenoid bone, similar to stem tetrapods such as embolomeres. This morphology is consistent in a second aïstopod, Coloraderpeton, although the details differ. Phylogenetic analysis, including critical new braincase data, places aïstopods deep on the tetrapod stem, whereas another major lepospondyl lineage is displaced into the amniotes. These results show that stem group tetrapods were much more diverse in their body plans than previously thought. Our study requires a change in commonly used calibration dates for molecular analyses, and emphasizes the importance of character sampling for early tetrapod evolutionary relationships.

Burn care in Los Angeles, California: LAC+USC experience 1994-2004.

PubMed

Garner, Warren L; Reiss, Matthew

2005-01-01

The LAC+USC Burn Center has admitted 3118 patients for treatment in the last 10 years. A majority of patients were young adults (1868), with the second largest group being small children (543). The ethnicity of the patients reflects the diverse nature of the population of Los Angeles County. Forty-eight percent of injuries were less than 5% TBSA and approximately 2% were greater than 60% TBSA. Eighty-two percent were accidental injuries. Sixty percent of admitted patients underwent skin grafting. Mortality was negligible in the group with burns over less than 10% of their body and very high (15/19), 79% in the most severely burned group. Further, there was a high correlation between age and mortality. Complications during treatment included: deep venous thrombosis 1% per year; pulmonary emboli in 5 patients; endotracheal tube dislodgment early or self-extubation about 1 month (11.3 per year); 4.5 patients per year who developed acute renal failure; abdominal compartment syndrome developed in 4.7 patients each year; heterotopic ossification was seen in 4 patients (0.4%); 4 patients (0.4%) developed stage II-IV pressure sores; hypothermia was present in 0.8% of patients.

Controlled Dual Growth Factor Delivery From Microparticles Incorporated Within Human Bone Marrow-Derived Mesenchymal Stem Cell Aggregates for Enhanced Bone Tissue Engineering via Endochondral Ossification.

PubMed

Dang, Phuong N; Dwivedi, Neha; Phillips, Lauren M; Yu, Xiaohua; Herberg, Samuel; Bowerman, Caitlin; Solorio, Loran D; Murphy, William L; Alsberg, Eben

2016-02-01

Bone tissue engineering via endochondral ossification has been explored by chondrogenically priming cells using soluble mediators for at least 3 weeks to produce a hypertrophic cartilage template. Although recapitulation of endochondral ossification has been achieved, long-term in vitro culture is required for priming cells through repeated supplementation of inductive factors in the media. To address this challenge, a microparticle-based growth factor delivery system was engineered to drive endochondral ossification within human bone marrow-derived mesenchymal stem cell (hMSC) aggregates. Sequential exogenous presentation of soluble transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) at various defined time courses resulted in varying degrees of chondrogenesis and osteogenesis as demonstrated by glycosaminoglycan and calcium content. The time course that best induced endochondral ossification was used to guide the development of the microparticle-based controlled delivery system for TGF-β1 and BMP-2. Gelatin microparticles capable of relatively rapid release of TGF-β1 and mineral-coated hydroxyapatite microparticles permitting more sustained release of BMP-2 were then incorporated within hMSC aggregates and cultured for 5 weeks following the predetermined time course for sequential presentation of bioactive signals. Compared with cell-only aggregates treated with exogenous growth factors, aggregates with incorporated TGF-β1- and BMP-2-loaded microparticles exhibited enhanced chondrogenesis and alkaline phosphatase activity at week 2 and a greater degree of mineralization by week 5. Staining for types I and II collagen, osteopontin, and osteocalcin revealed the presence of cartilage and bone. This microparticle-incorporated system has potential as a readily implantable therapy for healing bone defects without the need for long-term in vitro chondrogenic priming. Significance: This study demonstrates the regulation of chondrogenesis

Heterotopic Gastric Mucosa in the Distal Part of Esophagus in a Teenager: Case Report.

PubMed

Lupu, Vasile Valeriu; Ignat, Ancuta; Paduraru, Gabriela; Mihaila, Doina; Burlea, Marin; Ciubara, Anamaria

2015-10-01

Heterotopic gastric mucosa (HGM) of the esophagus is a congenital anomaly consisting of ectopic gastric mucosa. It may be connected with disorders of the upper gastrointestinal tract, exacerbated by Helicobacter pylori. The diagnosis of HGM is confirmed via endoscopy with biopsy. Histopathology provides the definitive diagnosis by demonstrating gastric mucosa adjacent to normal esophageal mucosa. HGM located in the distal esophagus needs differentiation from Barrett's esophagus. Barrett's esophagus is a well-known premalignant injury for adenocarcinoma of the esophagus. Malignant progression of HGM occurs in a stepwise pattern, following the metaplasia-dysplasia-adenocarcinoma sequence.We present a rare case of a teenage girl with HGM located in the distal esophagus, associated with chronic gastritis and biliary duodenogastric reflux. Endoscopy combined with biopsies is a mandatory method in clinical evaluation of metaplastic and nonmetaplastic changes within HGM of the esophagus.

Introducing Computed Tomography Standards for Age Estimation of Modern Australian Subadults Using Postnatal Ossification Timings of Select Cranial and Cervical Sites(.).

PubMed

Lottering, Nicolene; MacGregor, Donna M; Alston, Clair L; Watson, Debbie; Gregory, Laura S

2016-01-01

Contemporary, population-specific ossification timings of the cranium are lacking in current literature due to challenges in obtaining large repositories of documented subadult material, forcing Australian practitioners to rely on North American, arguably antiquated reference standards for age estimation. This study assessed the temporal pattern of ossification of the cranium and provides recalibrated probabilistic information for age estimation of modern Australian children. Fusion status of the occipital and frontal bones, atlas, and axis was scored using a modified two- to four-tier system from cranial/cervical DICOM datasets of 585 children aged birth to 10 years. Transition analysis was applied to elucidate maximum-likelihood estimates between consecutive fusion stages, in conjunction with Bayesian statistics to calculate credible intervals for age estimation. Results demonstrate significant sex differences in skeletal maturation (p < 0.05) and earlier timings in comparison with major literary sources, underscoring the requisite of updated standards for age estimation of modern individuals. © 2015 American Academy of Forensic Sciences.

A gastrocnemius heterotopical transplant model with end-to-side neurorraphy.

PubMed

Jaeger, Marcos Ricardo de Oliveira; Silva, Jefferson Luis Braga; Bain, James; Ely, Pedro Bins; Pires, Jefferson André; Ferreira, Lydia Masako

2014-01-01

To present an animal model to assess the effects of end-to-side innervation in the heterotopically transplanted model with reduced chances of neural contamination. The medial portion of the gastrocnemius muscle in wistar male rats was isolated and its pedicle dissected and performed a flap in the abdominal portion. To prevent neural contamination in the abdominal region, the muscle was wrapped with a Goretex(r) sheet. The specimens were divided into 2 groups (G). In G1 was performed an end-to-end suture between tibial nerve of the gastrocnemius and femoral motor nerve and between the saphenous sensory nerve and the motor nerve. In G2 was performed a end-to-side suture between the tibial nerve and the motor femoral and between the tibial nerve and saphenous motor nerve. The specimens were evaluated 60 days later to check the structure of the neurorraphy. Sections were obtained proximal and distal to the coaptation site. The medial gastrocnemius muscle had the advantage of maintaining visible mass after 60 days. No disruption of the coaptation site was found. No major injury to the donor nerve was seen in group 2. The proposed model is simple, reproduciple and prevent the neural contamination in the flap in end-to-side suture.

Noxious mechanical heterotopic stimulation induces inhibition of the spinal dorsal horn neuronal network: analysis of spinal somatosensory-evoked potentials.

PubMed

Meléndez-Gallardo, J; Eblen-Zajjur, A

2016-09-01

Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.

Heterotopic Ossification Following Extremity Blast Amputation: An Animal Model in the Sprague Dawley Rat

DTIC Science & Technology

2016-03-01

to their pre-injury baseline activities after a week. One animal assigned to the irradiation group died at two weeks post op of unknown causes and was...kg) and enrofloxacin (5 mg/kg) were administered subcutaneously for preemptive analge- sia and prophylactic antibacterial coverage, respectively. The...Buprenorphine (0.05 mg/kg) and enrofloxacin (5 mg/kg) were administered subcutaneously for preemptive analgesia and prophylactic antibacterial coverage

Combat-Related Heterotopic Ossification: Development of Animal Models for Identifying Mechanisms and Testing Therapeutics

DTIC Science & Technology

2016-03-01

to the systemic and perhaps local antimicrobial therapies geared towards decreasing bioburden in combat wounds. 6 Using our blast-related HO...Farms, Germantown, New York; 400 g to 510 g) that were housed in clean plastic cages on a 12-hour light/dark cycle with access to food (standard chow...inflammatory neuro- peptides . For example, substance-P, acting through the neu- rokinin-1 receptor (NK1), and calcitonin gene-related peptide (CGRP) result

Combat-Related Heterotopic Ossification: Development of Animal Models for Identifying Mechanisms and Testing Therapeutics

DTIC Science & Technology

2015-07-01

wound debridements in addition to the systemic and perhaps local antimicrobial therapies geared towards decreasing bioburden in combat wounds...housed in clean plastic cages on a 12-hour light/dark cycle with access to food (standard chow) and water ad libitum. They were allowed to acclima...Although not yet investigated in this model, possible causes for this include the release of inflammatory neuro- peptides . For example, substance-P

Heterotopic Ossification Following Extremity Blast Amputation: An Animal Model in the Sprague Dawley Rat

DTIC Science & Technology

2012-10-01

Buprenorphine (0.05 mg/kg) and 12 enrofloxacin (5 mg/kg) were administered subcutaneously for preemptive analgesia and 13 prophylactic antibacterial...cage with warmed bedding and was monitored until awakening from anesthesia. 19 Animals received antibiotics ( enrofloxacin , 5 mg/kg administered

Hormones and growth factors in the pathogenesis of spinal ligament ossification.

PubMed

Li, Hai; Jiang, Lei-Sheng; Dai, Li-Yang

2007-08-01

Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-beta (TGF-beta), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL.

Total elbow arthroplasty in primary osteoarthritis of the elbow.

PubMed

Kozak, T K; Adams, R A; Morrey, B F

1998-10-01

Primary osteoarthritis of the elbow is an infrequent condition typically managed by some form of debridement. There is no comment in the literature regarding prosthetic replacement for this condition. We report 5 patients (mean age, 68), with a minimum assessment of 3 years (range, 37-125 years) after total elbow arthroplasty. Complications in 4 patients included subluxation, fracture of a humeral component with particulate synovitis, heterotopic ossification, recurrent osteophyte formation, and transient ulnar neuropathy. Although revision was required in 2 of the 5, currently all experience had satisfactory outcomes. While replacement has proven ultimately to be a successful option for this high-demand patient group because of the high complication rate, we do not recommend replacement unless alternate operative options are deemed unacceptable.

Delayed ossification in Wistar rats induced by Morinda citrifolia L. exposure during pregnancy.

PubMed

Marques, Nelson Fernando Quallio; Marques, Ana Paula Bombonatto Mariano; Iwano, Ana Lívia; Golin, Munisa; De-Carvalho, Rosangela Ribeiro; Paumgartten, Francisco José Roma; Dalsenter, Paulo Roberto

2010-03-02

Different products of plant Morinda citrifolia L. (noni) have been marketed and used around the world based on properties described by Polynesian people that use them for more than 2000 years. Marketing of these products is based on their presumptive phytotherapic properties. However there is little scientific evidence about their safety, especially when used during pregnancy. Evaluate the possible developmental toxicity of the noni fruit aqueous extract and commercial product of TAHITIAN NONI juice in rats exposed during pregnancy. Pregnant Wistar rats were exposed by gavage to 7, 30 and 300 mg/kg bw (body weight) of noni aqueous extract or to 0.4, 2 and 20 mL/kg bw (body weight) of noni juice between day 7 and day 15 of pregnancy. Caesarean sections were performed on day 20 of pregnancy and reproductive parameters were evaluated. Implantations sites and postimplantation losses were recorded. Fetuses were weighted and examined for externally visible anomalies. After, the fetuses were cleared with KOH and the bones stained with alizarin red. Skeletal alterations of the skull, vertebral column, ribs, forelimbs, hindlimbs, sternum, sings of delayed ossification and variations were examined in accordance with pre-defined criteria and identified using harmonized and internationally accepted nomenclature recommended by the International Federation of Teratology Societies. Exposure with extract and juice of Morinda citrifolia did not induce maternal toxicity at the tested doses, but induced delayed ossification in fetuses. The exposure of pregnant rats to aqueous extract or juice Morinda citrifolia during organogenesis period may induce adverse effects on the normal development of fetuses. These findings indicate the need for further studies with noni derivates preceding their use in pregnant women. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Endochondral vs. intramembranous demineralized bone matrices as implants for osseous defects.

PubMed

Nidoli, M C; Nielsen, F F; Melsen, B

1999-05-01

This study focuses on the difference in regenerative capacity between endochondral and intramembranous demineralized bone matrices (DBMs) when implanted into bony defects. It also focuses on the possible influence of the type of skeletal recipient site (orthotopic or heterotopic). Of 34 Wistar rats, 10 served as a source of DBM, and 24 were divided into two groups of 12 animals. In group A identical defects were produced in the parietal bones, whereas in group B the defects were produced in each radius. The right defects were implanted with endochondral DBM and the left defects were implanted with intramembranous DBM. Descriptive and/or histomorphometric analyses were performed by means of light and polarized microscopy, and radiography (group B). Right and left data were compared to disclose differences in bone-healing capacity. The quantitative results demonstrated that endochondral DBM displays a greater regenerative capacity than intramembranous DBM when implanted heterotopically. The different clinical performances of endochondral and intramembranous bone grafts might be explained on the basis of the mechanical rather than the osteoinductive principle. The qualitative results suggest that the type of bone deposition induced by the DBMs is not related to the type of implanted DBM. Recipient site characteristics and/or environmental factors seem decisive in the occurrence of either types of ossification.

Biodegradable implants for Pipkin fractures.

PubMed

Prokop, Axel; Helling, Hanns-Joachim; Hahn, Ulrich; Udomkaewkanjana, Chira; Rehm, Klaus Emil

2005-03-01

The current study was designed to clarify whether biodegradable poly-L/DL lactide pins provide an operative alternative for fixation of Pipkin fractures. Nine patients with Pipkin fractures (one with Pipkin Type I, one with Pipkin Type II, and seven with Pipkin Type IV fractures) were treated surgically between 1996 and 2002. In all patients, the femoral head fractures were fixed with biodegradable, 2.7-mm and 2.0-mm polylactide pins. Eight patients were followed up for an average of 54.2 months. One patient died before the final followup. Eight fractures healed uneventfully. In one patient, a persisting femoral head defect led to posttraumatic arthritis requiring insertion of a femoral endoprosthesis at 1 year. The average range of motion of the affected hips of all patients at followup was 109 degrees -0 degrees -0 degrees in flexion and extension. External and internal rotation averaged 37 degrees -0 degrees -29 degrees . One patient had Brooker Grade I heterotopic ossification develop, and another had a Grade II heterotopic develop. Merle d'Aubigne and Postel ratings showed two excellent and five satisfactory results (average score, 13.1). Adverse effects from the polylactide implants were not observed. Pipkin fractures can be fixed successfully with biodegradable polylactide pins.

Intramembranous ossification of scleral ossicles in Chelydra serpentina.

PubMed

Franz-Odendaal, Tamara A

2006-01-01

Scleral ossicles are present in many reptiles, including turtles and birds. In both groups the sclerotic ring situated in the eye is composed of a number of imbricating scleral ossicles or plates. Despite this gross morphological similarity, Andrews (1996. An endochondral rather than a dermal origin for scleral ossicles in Cryptodiran turtles. J. Herpetol. 30, 257-260) reported that the scleral ossicles of turtles develop endochondrally unlike those in birds, which develop intramembranously after a complex epithelial-mesenchymal inductive event. This study re-explores one of the species examined by Andrews in order to determine the mode of ossification of scleral ossicles in turtles. A growth series of Chelydra serpentina embryos, including the stages examined by Andrews, were examined by staining separately for cartilage and bone. Results clearly contradict Andrews (1996) and show that the scleral ossicles of Chelydra serpentina develop similarly to those in birds. That is, they develop intramembranously without a cartilage precursor and are likely induced by transient scleral papillae. The sequence of scleral papillae development is broadly similar, but the papillae themselves are not as distinct as those seen in chicken embryos. This study has important consequences for understanding the homology of scleral ossicles among tetrapods.

PIXE study of the kinetics of biomaterials ossification

NASA Astrophysics Data System (ADS)

Weber, G.; Robaye, G.; Braye, F.; Oudadesse, H.; Irigaray, J. L.

1994-05-01

Biomaterials are frequently implanted in bones. This implantation is followed by a phenomenon of ossification. The purpose of this work was to study the time evolution of the gradient of characteristic atomic element's concentrations in the bone, the implant and the bone-implant interface. We have studied two types of neutral biomaterials: pure synthetic hydroxyapatite and porite's asteroid coral. The animal implantations have been made on sheep of the same age and sex having received the same basic diet. The implantations have been made in the cortical femur. On both sides of the implant, at the same distance, two screws were placed to allow further determination of the position of the implant. The PIXE method is particularly suitable here because of the possibility to analyze directly the samples without any preparation and to choose easily the dimensions of beam used for the gradient study. The X-rays have been detected with an ultra LEGe instead of the usual Si(Li) device to avoid the Si escape peak associated with the K α X-ray of calcium, the major constituent of bone. This peak is particularly disturbing here because its energy corresponds to the K α line of phosphorus, an important constituent of bone. The results of these determinations are presented and discussed.

Heterotopic salivary gland tissue: a case report demonstrating evolution and association with the branchial apparatus.

PubMed

Chang, Wen-Yu; Lee, Ka-Wo; Tsai, Kun-Bow; Chen, Gwo-Shing

2005-09-01

Heterotopic salivary gland tissue (HSGT) in the lower neck is an unusual developmental anomaly with characteristic clinical and microscopic findings. The exact embryogenesis remains unclear. This rare entity must be considered in the differential diagnosis of neck mass with fistula. We present a typical HSGT totally removed using the stepladder excision technique and showing an internal fistula. Interpretation of this case from the anatomical and pathological points of view, we support the argument that the embryogenesis of HSGT is more probably related to ectodermal heteroplasia of the precervical sinus of His and further conclude that an association with branchial cleft sinus may exist and cannot be seen as an exclusion criteria for diagnosis of HSGT. Due to possible but infrequent neoplastic transformation, it is important to check HSGT in every encountered cervical anomaly related to any branchial apparatus derived lesion.

Hormones and growth factors in the pathogenesis of spinal ligament ossification

PubMed Central

Li, Hai; Jiang, Lei-Sheng

2007-01-01

Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-β (TGF-β), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL. PMID:17426989

Isovolumic loading of the failing heart by intraventricular placement of a spring expander attenuates cardiac atrophy after heterotopic heart transplantation.

PubMed

Pokorný, Martin; Mrázová, Iveta; Šochman, Jan; Melenovský, Vojtěch; Malý, Jiří; Pirk, Jan; Červenková, Lenka; Sadowski, Janusz; Čermák, Zdeněk; Volenec, Karel; Vacková, Šárka; Maxová, Hana; Červenka, Luděk; Netuka, Ivan

2018-05-09

Cardiac atrophy is the most common complication of prolonged application of the left ventricle assist device in patients with advanced heart failure. Our aim was to evaluate the course of unloading-induced cardiac atrophy in rats with failing hearts, and to examine if increased isovolumic loading obtained by intraventricular implantation of an especially designed spring expander would attenuate this process. Heterotopic abdominal heart transplantation (HT x ) was used as a rat model of heart unloading. Heart failure (HF) was induced by volume overload achieved by creation of the aorto-caval fistula. The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart (HW) to the control heart. Isovolumic loading was increased by intraventricular implantation of a stainless steel three-branch spring expander. The course of cardiac atrophy was evaluated on days 7, 14, 21 and 28 after HT x Seven-days unloading by HT x in failing hearts sufficed to substantially decrease HW (-59 ± 3%), the decrease progressed when measured on days 14, 21 and 28 after HT x Implantation of the spring expander significantly reduced the decreases in whole HW at all the time-points (-39 ± 3 vs. -59 ± 3, -52 ± 2 vs. -69 ± 3, -51 ± 2 vs. - 71 ± 2 and -44 ± 2 vs. -71 ± 3%, respectively; p<0.05 in each case). We conclude that the enhanced isovolumic heart loading obtained by implantation of the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing rat heart. ©2018 The Author(s).

Role of heterotopic kidney auto-transplantation for renal artery aneurysms.

PubMed

Gwon, Jun G; Han, Duck J; Cho, Yong-Pil; Kim, Young H; Kwon, Tae-Won

2018-06-01

To assess the applicability and surgical outcomes of ex vivo repair with heterotopic kidney auto-transplantation (HKA) for the treatment of renal artery aneurysms (RAA).We retrospectively examined 36 cases presenting with RAA from September 2005 to June 2016. Patient demographics, estimated glomerular filtration rate (eGFR), and common vascular risk factors were evaluated. Patients were classified into 3 groups: those who received endovascular treatment, in situ open surgical repair, or ex vivo repair with HKA. The findings were compared among the groups.The endovascular repair, in situ open repair, and ex vivo repair with HKA groups included 14, 9, and 13 patients, respectively (mean follow-up, 30.42 ± 30.54 months). The eGFR (P = .32) and number of anti-hypertension medications (P = .33) did not significantly differ among the groups. Moreover, 3 renal infarctions were detected in the endovascular group and only 1 was detected in the in situ repair group. One patient in the endovascular repair group required dialysis due to renal failure. Patients in the ex vivo repair with HKA group did not exhibit any complications.With safety and effectiveness comparable to other RAA treatment methods, ex vivo repair with HKA for RAA treatment appears suitable particularly in cases with complicated renal artery branch aneurysm and marginal renal function.

Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model.

PubMed

Greiten, Lawrence E; McKellar, Stephen H; Rysavy, Joseph; Schaff, Hartzell V

2014-05-01

Warfarin is used to reduce the risk of stroke and thromboembolic complications in patients with mechanical heart valves. Yet, despite frequent blood testing, its poor pharmacokinetic and pharmacodynamic profiles often result in variable therapeutic levels. Rivaroxaban is a direct competitive factor Xa inhibitor that is taken orally. It inhibits the active site of factor Xa without the need for the cofactor antithrombin, and thus, its mechanism of action is differentiated from that of the fractionated heparins and indirect factor Xa inhibitors. No in vivo data exist regarding the effectiveness of rivaroxaban in preventing thromboembolic complications of mechanical heart valves. We tested the hypothesis that rivaroxaban is as effective as enoxaparin for thromboprophylaxis of mechanical valves that use a previously described heterotopic aortic valve porcine model. A modified bileaflet mechanical valved conduit that bypassed the native, ligated descending thoracic aorta was implanted into 30 swine. Postoperatively, the animals were randomly assigned to groups receiving no anticoagulation (n = 10), enoxaparin at 2 mg/kg subcutaneously twice daily (n = 10) or rivaroxaban at 2 mg/kg orally twice daily (n = 10). The amount of valve thrombus was measured on post-implantation day 30 as the primary end point. Quantitative evaluation of radiolabelled platelet deposition on the valve prostheses was done and embolic and haemorrhagic events were measured as secondary end points. Animals with no anticoagulation had a thrombus mean of 759.9 mg compared with 716.8 mg with enoxaparin treatment and 209.6 mg with rivaroxaban treatment (P = 0.05 for enoxaparin vs rivaroxaban). Similarly, the mean number of platelets deposited on the valve prosthesis was lower in the rivaroxaban group (6.13 × 10(9)) than in the enoxaparin group (3.03 × 10(10)) (P = 0.03). In this study, rivaroxaban was more effective than enoxaparin for short-term thromboprophylaxis of mechanical valve prosthetics in

Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head

PubMed Central

Roybal, Paul G.; Wu, Nancy L.; Sun, Jingjing; Ting, Man-chun; Schaefer, Christopher; Maxson, Robert E.

2011-01-01

In an effort to understand the morphogenetic forces that shape the bones of the skull, we inactivated Msx1 and Msx2 conditionally in neural crest. We show that Wnt1-Cre inactivation of up to three Msx1/2 alleles results in a progressively larger defect in the neural crest-derived frontal bone. Unexpectedly, in embryos lacking all four Msx1/2 alleles, the large defect is filled in with mispatterned bone consisting of ectopic islands of bone between the reduced frontal bones, just anterior to the parietal bones. The bone is derived from neural crest, not mesoderm, and, from DiI cell marking experiments, originates in a normally non-osteogenic layer of cells through which the rudiment elongates apically. Associated with the heterotopic osteogeneis is an upregulation of Bmp signaling in this cell layer. Prevention of this upregulation by implantation of noggin-soaked beads in head explants also prevented heterotopic bone formation. These results suggest that Msx genes have a dual role in calvarial development: They are required for the differentiation and proliferation of osteogenic cells within rudiments, and they are also required to suppress an osteogenic program in a cell layer within which the rudiments grow. We suggest that the inactivation of this repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised. PMID:20398647

Revision hip preservation surgery with hip arthroscopy: clinical outcomes.

PubMed

Domb, Benjamin G; Stake, Christine E; Lindner, Dror; El-Bitar, Youseff; Jackson, Timothy J

2014-05-01

To analyze and report the clinical outcomes of a cohort of patients who underwent revision hip preservation with arthroscopy and determine predictors of positive and negative outcomes. During the study period from April 2008 to December 2010, all patients who underwent revision hip preservation with arthroscopy were included. This included patients who had previous open surgery and underwent revision with arthroscopy. Patient-reported outcome (PRO) scores were obtained preoperatively and at 3-month, 1-year, 2-year, and 3-year follow-up time points. Any revision surgeries and conversions to total hip arthroplasty were noted. A multiple regression analysis was performed to look for positive and negative predictive factors for improvement in PROs after revision hip arthroscopy. Forty-seven hips in 43 patients had completed 2 years' follow-up or needed total hip arthroplasty. The mean length of follow-up was 29 months (range, 24 to 47 months). Of the hips, 31 (66%) had either unaddressed or incompletely treated femoroacetabular impingement. There was a significant improvement in all PRO scores at a mean of 29 months after revision (P < .0001). The visual analog scale score improved from 7.3 ± 1.5 to 3.9 ± 2.5 (P < .0001). Improvements in the Non-Arthritic Hip Score of at least 10 points and 20 points were found in 28 hips (65%) and 19 hips (44%), respectively. Four hips in 3 patients required conversion to total hip arthroplasty. Positive predictive factors for PRO improvement were previous open surgery, pincer impingement, cam impingement, symptomatic heterotopic ossification, and segmental labral defects treated with labral reconstruction. On the basis of multiple PROs, revision hip preservation with hip arthroscopy can achieve moderately successful outcomes and remains a viable treatment strategy after failed primary hip preservation surgery. Preoperative predictors of success after revision hip arthroscopy include segmental labral defects, unaddressed or

Best Practices During Hip Arthroscopy: Aggregate Recommendations of High-Volume Surgeons.

PubMed

Gupta, Asheesh; Suarez-Ahedo, Carlos; Redmond, John M; Gerhardt, Michael B; Hanypsiak, Bryan; Stake, Christine E; Finch, Nathan A; Domb, Benjamin G

2015-09-01

To survey surgeons who perform a high volume of hip arthroscopy procedures regarding their operative technique, type of procedure, and postoperative management. We conducted a cross-sectional survey of 27 high-volume orthopaedic surgeons specializing in hip arthroscopy to report their preferences and practices related to their operative practice and postoperative rehabilitation protocol. All participants completed the survey in person in an anonymous fashion during a meeting of the American Hip Institute. All surgeons perform hip arthroscopy with the patient in the supine position, accessing the central compartment of the hip initially, using intraoperative fluoroscopy. All surgeons perform labral repair (100%), with the majority performing labral reconstructions (77.8%) and gluteus medius repairs (81.5%). There is variability in the type of anchors used during labral repair. Most surgeons perform capsular closure in most cases (88.9%), inject either intra-articular cortisone or platelet-rich plasma at the conclusion of the procedure (59%), and prescribe a postoperative hip brace for some or all patients (59%). There is considerable variability in rehabilitation protocols. All surgeons routinely prescribe postoperative heterotopic ossification prophylaxis to their patients, with most surgeons (88.9%) prescribing a nonsteroidal anti-inflammatory medication for 3 weeks. Forty percent of the respondents use the modified Harris Hip Score as the most important outcome measure. Consistent practices such as use of intraoperative fluoroscopy, heterotopic ossification prophylaxis, and labral repair skills were identified by surveying 27 hip arthroscopy surgeons at high-volume centers. Most of the surgeons performed routine capsular closure unless underlying conditions precluded capsular release or plication. The survey identified higher variability between surgeons regarding postoperative rehabilitation protocols and use of intra-articular pharmacologic injections at the

Phenotypic and Genotypic Characterization and Treatment of a Cohort with Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome

PubMed Central

Ramnitz, Mary Scott; Gourh, Pravitt; Goldbach-Mansky, Raphaela; Wodajo, Felasfa; Ichikawa, Shoji; Econs, Michael J.; White, Kenneth; Molinolo, Alfredo; Chen, Marcus Y.; Heller, Theo; Del Rivero, Jaydira; Seo-Mayer, Patricia; Arabshahi, Bita; Jackson, Malaka B.; Hatab, Sarah; McCarthy, Edward; Guthrie, Lori C.; Brillante, Beth A.; Gafni, Rachel I.; Collins, Michael T.

2016-01-01

Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated while iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in 7 subjects; no causative mutation was found in the eighth. Biopsies from 4 subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in 1 subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the 2 subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and peri-lesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations

Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report.

PubMed

Matsunaga, Shunji; Koga, Hiroaki; Kawabata, Naoya; Kawamura, Ichiro; Otusji, Masaki; Imakiire, Takanori; Komiya, Setsuro

2008-01-01

The pathogenesis of ossification of the posterior longitudinal ligaments (OPLL) has not been clarified. We here report dizygotic twin sisters with OPLL of the cervical spine and propose a new pathogenesis of OPLL. This is the first report of dizygotic twins with OPLL. The twins suffered from schizophrenia, which might be related to the pathogenesis of OPLL. In addition, we investigated the occurrence of OPLL in 30 patients with schizophrenia who had been admitted to a mental hospital. OPLL of the cervical spine was found in six (20%) of them, with an incidence almost five times higher than the incidence of OPLL among the general population in Japan. Schizophrenia may have a increased susceptibility to OPLL.

Role of Runx2 polymorphisms in risk and prognosis of ossification of posterior longitudinal ligament.

PubMed

Chang, Feng; Li, Lijun; Gao, Gang; Ding, Shengqiang; Yang, Jincai; Zhang, Ting; Zuo, Genle

2017-07-01

Our study was aimed at finding out if Runx2 SNPs (single-nucleotide polymorphisms) are related to susceptibility to and prognosis of ossification of posterior longitudinal ligament (OPLL). We selected 80 OPLL patients and another 80 independent patients without OPLL from September 2013 to November 2014. Serum was collected to detect the genotypes of rs1321075, rs12333172, and rs1406846 on Runx2 with direct sequencing analysis. Differences in clinical characteristics, including age, weight, height, sex ratio, as well as smoking and drinking history, between OPLL and control groups appeared to be insignificant (all P-value >.05). The allele of rs1406846 (A) emerged as a key element in raising OPLL risk with the biggest statistical significance (P<.001). Conversely, alleles of rs967588 (T) and rs16873379 (C) were associated with reduced predisposition to OPLL less remarkably (both P=.033). Regarding rs16873379, the case group exhibited a smaller frequency of homozygote CC in comparison with TT genotype than the control group (P=.016). Furthermore, the improvement rate based on calculation of JOA score suggested that genotype AA of rs6908650 was beneficial for OPLL patients' recovery from posterior laminoplasty surgery (P<.05), while genotypes of rs16873379 (CC), rs1406846 (AA), and rs2677108 (CC) significantly restrained this process (P<.05). Besides, rs16873379, rs1406846, and rs2677108 were significantly associated with number of ossification segments (P<.05). Runx2 SNPs (e.g., rs16873379, rs1406846, and rs2677108) were strongly correlated with onset and treatment efficacy of OPLL, and they might regulate severity of OPLL. © 2016 Wiley Periodicals, Inc.

Somitic disruption of GNAS in chick embryos mimics progressive osseous heteroplasia

PubMed Central

Cairns, Dana M.; Pignolo, Robert J.; Uchimura, Tomoya; Brennan, Tracy A.; Lindborg, Carter M.; Xu, Meiqi; Kaplan, Frederick S.; Shore, Eileen M.; Zeng, Li

2013-01-01

Progressive osseous heteroplasia (POH) is a rare developmental disorder of heterotopic ossification (HO) caused by heterozygous inactivating germline mutations in the paternal allele of the GNAS gene. Interestingly, POH lesions have a bewildering mosaic distribution. Using clinical, radiographic, and photographic documentation, we found that most of the 12 individuals studied had a lesional bias toward one side or the other, even showing exclusive sidedness. Most strikingly, all had a dermomyotomal distribution of HO lesions. We hypothesized that somatic mutations in a progenitor cell of somitic origin may act on a background of germline haploinsufficiency to cause loss of heterozygosity at the GNAS locus and lead to the unilateral distribution of POH lesions. Taking advantage of the chick system, we examined our hypothesis by mimicking loss of heterozygosity of GNAS expression using dominant-negative GNAS that was introduced into a subset of chick somites, the progenitors that give rise to dermis and muscle. We observed rapid ectopic cartilage and bone induction at the axial and lateral positions in a unilateral distribution corresponding to the injected somites, which suggests that blocking GNAS activity in a targeted population of progenitor cells can lead to mosaic ectopic ossification reminiscent of that seen in POH. PMID:23863715

PROGRESSIVE OSSIFYING FIBRODYSPLASIA: CASE REPORT

PubMed Central

Romani, Fabiana; de Menezes Karam, Simone

2015-01-01

Progressive ossifying fibrodysplasia is a rare genetic disease that affects one individual in every two million births. Its main consequence is heterotopic ossification, i.e. formation of additional bone in abnormal locations. It is an autosomal dominant disease, usually caused by a new mutation in the ACVR1 receptor gene, which is in the signaling pathway for bone morphogenic protein. This abnormality is not related to gender, ethnicity or consanguinity. The present study reports the case of A.C., a 17-year-old girl. Her clinical investigation began at the age of four years, but she was only diagnosed with FOP at the age of 15 years, after being evaluated by several specialists in different centers. The patient has two siblings, but her family history did not reveal any similar cases. PMID:27047836

Bipolar Hemarthroplasty Using Cementless Conical Stem for Treatment of Dorr Type B and C Femoral Neck Fracture.

PubMed

Kang, Jeong Hoon; Lee, Sang Hong; Jung, Sung

2015-12-01

The current study aims to evaluate the clinical and the radiological outcome of bipolar hemiarthroplasty using cementless cone stem to treat osteoporotic femoral neck fracture and compare the results according to the proximal femur geometry. Seventy-five hips (75 patients) that underwent bipolar hemiarthroplasty with cementless cone stem between September 2006 and December 2011 were analyzed. The minimum follow-up period was 3 years. Thirty-three hips were classified as type B and 41 as type C. The clinical outcome was assessed using Harris hip score and the walking ability score. Radiographic evaluation was performed to evaluate the stability of the prosthesis. At the most recent follow up, the mean Harris hip score was 86 (range, 70-92) and 65% recovered to preoperative ambulatory status. In the radiographic exam, stable stem fixation was achieved in all cases. For the complications, eight hips developed deep vein thrombosis while three hips showed heterotopic ossification. Dislocation and delayed deep infection occurred in one hip resepectively. There were no significance differences in Harris hip score and walking ability score when the type B group was compare with the type C. Bipolar hemiarthroplasty with cementless cone stem showed an excellent early outcome both clinically and radiographically regardless of the shape of the proximal femur. We believe this prosthesis can provide early stability to the Dorr type B and C femur and is an effective treatment for treating osteoporotic femoral neck fracture.

Investigation of a Translatable Animal Model in Order to Understand the Etiology of Heterotopic Ossification

DTIC Science & Technology

2017-09-01

dB levels that were made by the AID without attenuation, we performed this testing in a cinderblock-based room with metal ducting, cement floors and... steel -framed ceilings (Figure 7). 8 Figure 7: Image of a corner of the cinderblock room in which testing has been performed. To measure

Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice.

PubMed

Zhang, Zhongrong; Leung, Wing Nang; Li, Gang; Lai, Yau Ming; Chan, Chun Wai

2016-12-01

Osthole has been found to restore bone mass in preclinical osteoporotic models. In the present study, we investigated the effects of osthole on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with 20 mg/kg osthole and vehicle solvent daily from week 1 post-operation. Fracture callus were analyzed by plain radiography, micro-computed tomography, histology, molecular imaging and immunohistochemistry and tartrate-resistant acid phosphatase staining. Results demonstrated that osthole treatment enhanced removal of cartilage and bony union during reparative stage without significant interfering on remodeling process. In vivo molecular imaging showed bone formation rate of the treatment group was almost twofold of control group at week 2 post-operation. Osthole augmented the expression of alkaline phosphatase and collagen type X in hypertrophic chondrocytes as well as expression of bone morphogenetic protein-2, osteocalcin and alkaline phosphatase in osteoblastic cells, indicating it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during endochondral healing. In summary, osthole promotes endochondral ossification via upregulation of maturation osteogenic marker genes in chondrocytes and subsequently accelerates fracture repair and bony fusion.

Qualitative and quantitative evaluation of avian demineralized bone matrix in heterotopic beds.

PubMed

Reza Sanaei, M; Abu, Jalila; Nazari, Mojgan; A B, Mohd Zuki; Allaudin, Zeenathul N

2013-11-01

To evaluate the osteogenic potential of avian demineralized bone matrix (DBM) in the context of implant geometry. Experimental. Rock pigeons (n = 24). Tubular and chipped forms of DBM were prepared by acid demineralization of long bones from healthy allogeneic donors and implanted bilaterally into the pectoral region of 24 pigeons. After euthanasia at 1, 4, 6, 8, 10, and 12 weeks, explants were evaluated histologically and compared by means of quantitative (bone area) and semi quantitative measures (scores). All explants had new bone at retrieval with the exception of tubular implants at the end of week 1. The most reactive part in both implants was the interior region between the periosteal and endosteal surfaces followed by the area at the implant-muscle interface. Quantitative measurements demonstrated a significantly (P = .012) greater percentage of new bone formation induced by tubular implants (80.28 ± 8.94) compared with chip implants (57.64 ± 3.12). There was minimal inflammation. Avian DBM initiates heterotopic bone formation in allogeneic recipients with low grades of immunogenicity. Implant geometry affects this phenomenon as osteoconduction appeared to augment the magnitude of the effects in larger tubular implants. © Copyright 2013 by The American College of Veterinary Surgeons.

Gelatin device for the delivery of growth factors involved in endochondral ossification.

PubMed

Ahrens, Lucas A J; Vonwil, Daniel; Christensen, Jon; Shastri, V Prasad

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo.

Gelatin device for the delivery of growth factors involved in endochondral ossification

PubMed Central

Ahrens, Lucas A. J.; Vonwil, Daniel; Christensen, Jon

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo. PMID:28380024

R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification

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

Takegami, Yasuhiko; Department of Orthopaedic Surgery, Nagoya University School of Medicine, Nagoya; Ohkawara, Bisei

Endochondral ossification is a crucial process for longitudinal growth of bones. Differentiating chondrocytes in growth cartilage form four sequential zones of proliferation, alignment into column, hypertrophy, and substitution of chondrocytes with osteoblasts. Wnt/β-catenin signaling is essential for differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation remains unknown. Here we report that growth cartilage of Rspo2-knockout mice shows a decreased amount of β-catenin and increased amounts collagen type II (CII) and Sox9 in the abnormally extended proliferating zone. Inmore » contrast, expression of collagen type X (CX) in the hypertrophic zone remains unchanged. Differentiating chondrogenic ATDC5 cells, mimicking proliferating chondrocytes, upregulate Rspo2 and its putative receptor, Lgr5, in parallel. Addition of recombinant human Rspo2 to differentiating ATDC5 cells decreases expressions of Col2a1, Sox9, and Acan, as well as production of proteoglycans. In contrast, lentivirus-mediated knockdown of Rspo2 has the opposite effect. The effect of Rspo2 on chondrogenic differentiation is mediated by Wnt/β-catenin signaling, and not by Wnt/PCP or Wnt/Ca{sup 2+} signaling. We propose that Rspo2 activates Wnt/β-catenin signaling to reduce Col2a1 and Sox9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. - Highlights: • Rspo2 is a secreted activator of Wnt, and its knockout shows extended proliferating chondrocytes in endochondral ossification. • In proliferating chondrocytes of Rspo2-knockout mice, Sox9 and collagen type 2 are increased and β-catenin is decreased. • Rspo2 and its receptor Lgr5, as well as Sox9 and collagen type 2, are expressed in differentiating ATDC5 chondrogenic cells. • In ATDC5 cells, Rspo2 decreases

Management of cervical myelopathy due to ossification of posterior longitudinal ligament in a patient with Alström syndrome.

PubMed

Kanna, Rishi Mugesh; Gradil, Daniela; Boszczyk, Bronek M

2012-12-01

Alström syndrome (AS) is a rare autosomal recessive genetic disorder with multisystemic involvement characterised by early blindness, hearing loss, obesity, insulin resistance, diabetes mellitus, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. The clinical features, time of onset and severity can vary greatly among different patients. Many of the phenotypes are often not present in infancy but develop throughout childhood and adolescence. Recessively inherited mutations in ALMS1 gene are considered to be responsible for the causation of AS. Musculoskeletal manifestations including scoliosis and kyphosis have been previously described. Here, we present a patient with AS who presented with cervical myelopathy due to extensive flowing ossification of the anterior and posterior longitudinal ligaments of the cervical spine resulting in cervical spinal cord compression. The presence of an auto-fused spine in an acceptable sagittal alignment, in the background of a constellation of medical comorbidities, which necessitated a less morbid surgical approach, favored a posterior cervical laminectomy decompression in this patient. Postoperatively, the patient showed significant neurological recovery with improved function. Follow-up MRI showed substantial enlargement of the spinal canal with improved space available for the spinal cord. The rarity of the syndrome, cervical myelopathy due to ossified posterior longitudinal ligament as a disease phenotype and the treatment considerations for performing a posterior cervical decompression have been discussed in this Grand Rounds' case presentation.

Cellular and morphological aspects of fibrodysplasia ossificans progressiva

PubMed Central

Martelli, Anderson; Santos, Arnaldo Rodrigues

2014-01-01

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease that causes bone formation within the muscles, tendons, ligaments and connective tissues. There is no cure for this disorder and only treatment of the symptoms is available. The purpose of this study was to review the literature and describe the clinical, cellular and molecular aspects of FOP. The material used for the study was obtained by reviewing scientific articles published in various literature-indexed databases. In view of its rarity and of the lack of insightful information and the unpredictability of its course, FOP is a challenging disorder for professionals who are confronted by it. However, this rare disease raises a great deal of interest because understanding the mechanism of mature bone formation can encourage research lines related to bone regeneration and the prevention of heterotopic ossification. PMID:25482313

Myositis ossificans traumatica of the medial pterygoid muscle following a third molar extraction.

PubMed

Torres, A M; Nardis, A C; da Silva, R A; Savioli, C

2015-04-01

Myositis ossificans (MO) is a rare disease involving heterotopic ossification in the muscle or soft tissue. Myositis ossificans traumatica (MOT) disease presents as a calcification within the injured muscle, resulting from a single or repetitive injury. There are few reports of MOT in the masticatory muscles. The case of a patient with MOT in the medial pterygoid muscle caused by a complication related to the extraction of an erupted upper third molar is reported. The major symptom was severe trismus. Despite surgical treatment, the disease relapsed. MOT can lead to serious consequences for the patient. Its aetiopathogenesis needs to be better understood, so that the most appropriate treatment is established and relapses are minimized. This will improve the quality of life of these patients. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

PubMed Central

Imamura, Taisuke; Komatsu, Shuhei; Ichikawa, Daisuke; Kobayashi, Hiroki; Miyamae, Mahito; Hirajima, Shoji; Kawaguchi, Tsutomu; Kubota, Takeshi; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Ogiso, Kiyoshi; Yagi, Nobuaki; Yanagisawa, Akio; Ando, Takashi; Otsuji, Eigo

2015-01-01

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland (HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery (LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor (SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm into the submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG. PMID:26306144

Comparison of ossification of demineralized bone, hydroxyapatite, Gelfoam, and bone wax in cranial defect repair.

PubMed

Papay, F A; Morales, L; Ahmed, O F; Neth, D; Reger, S; Zins, J

1996-09-01

Demineralized bone allografts in the repair of calvarial defects are compared with other common bone fillers. This study uses a video-digitizing radiographic analysis of calvarial defect ossification to determine calcification of bone defects and its relation to postoperative clinical examination and regional controls. The postoperative clinical results at 3 months demonstrated that bony healing was greatest in bur holes filled with demineralized bone and hydroxyapatite. Radiographic analysis demonstrated calcification of demineralized bone-filled defects compared to bone wax- and Gelfoam-filled regions. Hydroxyapatite granules are radiographically dense, thus not allowing accurate measurement of true bone healing. The results suggest that demineralized bone and hydroxyapatite provide better structural support via bone healing to defined calvarial defects than do Gelfoam and bone wax.

Successful treatment algorithm for evaluation of early pregnancy after in vitro fertilization.

PubMed

Cookingham, Lisa Marii; Goossen, Rachel P; Sparks, Amy E T; Van Voorhis, Bradley J; Duran, Eyup Hakan

2015-10-01

To evaluate a prospectively implemented clinical algorithm for early identification of ectopic pregnancy (EP) and heterotopic pregnancy (HP) after assisted reproductive technology (ART). Analysis of prospectively collected data. Academic medical center. All ART-conceived pregnancies between January 1995 and June 2013. Early pregnancy monitoring via clinical algorithm with all pregnancies screened using human chorionic gonadotropin (hCG) levels and reported symptoms, with subsequent early ultrasound evaluation if hCG levels were abnormal or if the patient reported pain or vaginal bleeding. Algorithmic efficiency for diagnosis of EP and HP and their subsequent clinical outcomes using a binary forward stepwise logistic regression model built to determine predictors of early pregnancy failure. Of the 3,904 pregnancies included, the incidence of EP and HP was 0.77% and 0.46%, respectively. The algorithm selected 96.7% and 83.3% of pregnancies diagnosed with EP and HP, respectively, for early ultrasound evaluation, leading to earlier treatment and resolution. Logistic regression revealed that first hCG, second hCG, hCG slope, age, pain, and vaginal bleeding were all independent predictors of early pregnancy failure after ART. Our clinical algorithm for early pregnancy evaluation after ART is effective for identification and prompt intervention of EP and HP without significant over- or misdiagnosis, and avoids the potential catastrophic morbidity associated with delayed diagnosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors

PubMed Central

Qian, Guofeng; Karnati, Srikanth; Baumgart-Vogt, Eveline

2015-01-01

Ossification defects leading to craniofacial dysmorphism or rhizomelia are typical phenotypes in patients and corresponding knockout mouse models with distinct peroxisomal disorders. Despite these obvious skeletal pathologies, to date no careful analysis exists on the distribution and function of peroxisomes in skeletal tissues and their alterations during ossification. Therefore, we analyzed the peroxisomal compartment in different cell types of mouse cartilage and bone as well as in primary cultures of calvarial osteoblasts. The peroxisome number and metabolism strongly increased in chondrocytes during endochondral ossification from the reserve to the hypertrophic zone, whereas in bone, metabolically active osteoblasts contained a higher numerical abundance of this organelle than osteocytes. The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11β gene expression. During culture, calvarial pre-osteoblasts differentiated into secretory osteoblasts accompanied by peroxisome proliferation and increased levels of peroxisomal genes and proteins. Since many peroxisomal genes contain a PPAR-responsive element, we analyzed the gene expression of PPARɑ/ß/ɣ in calvarial osteoblasts and MC3T3-E1 cells, revealing higher levels for PPARß than for PPARɑ and PPARɣ. Treatment with different PPAR agonists and antagonists not only changed the peroxisomal compartment and associated gene expression, but also induced complex alterations of the gene expression patterns of the other PPAR family members. Studies in M3CT3-E1 cells showed that the PPARß agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat), whereas the PPARß antagonist GSK0660 led to repression of the PPRE and a decrease of the corresponding mRNA levels. In the same way, treatment of calvarial osteoblasts with GW0742 increased in peroxisome number and related gene expression

Suppressing Mesenchymal Stem Cell Hypertrophy and Endochondral Ossification in 3D Cartilage Regeneration with Nanofibrous Poly(l-Lactic Acid) Scaffold and Matrilin-3.

PubMed

Liu, Qihai; Wang, Jun; Chen, Yupeng; Zhang, Zhanpeng; Saunders, Laura; Schipani, Ernestina; Chen, Qian; Ma, Peter X

2018-06-22

Articular cartilage has a very limited ability to self-heal after injury or degeneration due to its low cellularity, poor proliferative activity, and avascular nature. Current clinical options are able to alleviate patient suffering, but cannot sufficiently regenerate the lost tissue. Biomimetic scaffolds that recapitulate the important features of the extracellular matrix (ECM) of cartilage are hypothesized to be advantageous in supporting cell growth, chondrogenic differentiation, and integration of regenerated cartilage with native cartilage, ultimately restoring the injured tissue to its normal function. It's a challenge to support and maintain articular cartilage regenerated by bone marrow-derived mesenchymal stem cells (BMSCs), which are prone to hypertrophy and endochondral ossification after implanted in vivo. In the present work, a nanofibrous poly(l-lactic acid) (NF PLLA) scaffold developed by our group was utilized because of the desired highly porous structure, high interconnectivity, collagen-like NF architecture to support rabbit BMSCs for articular cartilage regeneration. We further hypothesized that Matrilin-3 (MATN3), a non-collagenous, cartilage-specific ECM protein, would enhance the microenvironment of the NF PLLA scaffold for cartilage regeneration and maintaining its property. To test this hypothesis, we seeded BMSCs on the NF PLLA scaffold with or without MATN3. We found that MATN3 suppresses hypertrophy in this 3D culture system in vitro. Subcutaneous implantation of the chondrogenic cell/scaffold constructs in a nude mouse model showed that pretreatment with MATN3 was able to maintain chondrogenesis and prevent hypertrophy and endochondral ossification in vivo. These results demonstrate that the porous NF PLLA scaffold treated with MATN3 represents an advantageous 3D microenvironment for cartilage regeneration and phenotype maintenance, and is a promising strategy for articular cartilage repair. Articular cartilage defects, caused by trauma

Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): Inflammation in OPLL.

PubMed

Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Seki, Shoji; Suzuki, Kayo; Yahara, Yasuhito; Makino, Hiroto; Kitajima, Isao; Kimura, Tomoatsu

2017-01-01

Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of ligamentous tissue by ectopic new bone formation. OPLL causes narrowing of the spinal canal, resulting in neurological impairment. However, the pathogenesis of OPLL has not been fully elucidated. We investigated whether inflammation occurs in OPLL or not using high-sensitivity CRP (hs-CRP) in a case-control study. This study included 103 patients with OPLL in the patient group and 95 age- and sex-matched volunteers with degenerative spinal disease in the control group. Of the 103 OPLL patients, 88 patients who were available for more than 2 years follow-up were checked for OPLL progression. A blood sample was obtained and Hs-CRP, and other routine data, including total protein (TP), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glucose (Glu), calcium (Ca), inorganic phosphate (Pi), white blood cell count (WBC), hemoglobin (Hb) and platelet (PLT), were analyzed. The data were compared between the patients with OPLL and the controls. The severity of the ossified lesions in the whole spine were evaluated by the ossification index (OS index) in patients with OPLL. The data were also compared between the patients with OPLL progression (the progression group) and the patients without OPLL progression (the non-progression group). In the results, the mean hs-CRP in the OPLL group was higher than that in the controls. The Pi in the OPLL group was lower than that in the control group. A negative correlation was found between the Pi and the OS index. The mean hs-CRP in the progression group was higher than that in the non-progression group. There was a positive correlation between the average length of the OPLL progression per year and the hs-CRP. The results may suggest the occurrence of local inflammation in OPLL and the inflammation might cause OPLL progression. These facts are important for understanding the pathology of OPLL.

Postoperative Paralysis From Thoracic Ossification of Posterior Longitudinal Ligament Surgery Risk Factor of Neurologic Injury: Nationwide Multiinstitution Survey.

PubMed

Ito, Zenya; Matsuyama, Yukihiro; Ando, Muneharu; Kawabata, Shigenori; Kanchiku, Tsukasa; Kida, Kazunobu; Fujiwara, Yasushi; Yamada, Kei; Yamamoto, Naoya; Kobayashi, Sho; Saito, Takanori; Wada, Kanichiro; Tadokoro, Nobuaki; Takahashi, Masato; Satomi, Kazuhiko; Shinomiya, Kenichi; Tani, Toshikazu

2016-10-01

Retrospective case-control study. The purpose of this study was to examine the factors of postoperative paralysis in patients who have undergone thoracic ossification of posterior longitudinal ligament (OPLL) surgery. A higher percentage of thoracic OPLL patients experience postoperative aggravation of paralysis than cervical OPLL patients, including patients that presented great difficulties in treatment. However, there were a few reports to prevent paralysis thoracic OPLL. The 156 patients who had received thoracic OPLL surgery were selected as the subjects of this study. The items for review were the duration of disease; the preoperative muscle strength (Muscle Manual Testing); OPLL levels (T1/2-4/5: high, T5/6-8/9: middle, and T9/10-11/12: low); the spinal canal occupancy ratio; the ratio of yellow ligament ossification as a complication; the ratio of transcranial-motor evoked potential (Tc-MEP) derivation; the preoperative/postoperative kyphotic angles in the thoracic vertebrae; the correction angle of kyphosis; the duration of surgery; and the amount of bleeding. The subjects were divided into two groups based on the absence or presence of postoperative paralysis to determine the factors of postoperative paralysis. Twenty-three patients (14.7%) exhibited postoperative paralysis. Multivariate analysis identified factors associated with postoperative paralysis: the duration of disease (odds ratio, OR = 3.3); the correction angle of kyphosis (OR = 2.4); and the ratio of Tc-MEP derivation (OR = 2.2). The risk factors of postoperative paralysis are a short duration of disease and a small correction angle of kyphosis. In addition, ratios of Tc-MEP derivation below 50% may anticipate paralysis. 4.

Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus

PubMed Central

Chong, Vui Heng

2013-01-01

Heterotopic gastric mucosa of the proximal esophagus (HGMPE), also referred to as “inlet patch” or “cervical inlet patch”, is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%. Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints. Most consider HGMPE as clinically irrelevant entity. The clinical significance of HGMPE is mainly acid related or neoplastic transformation. The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20% to as high as 73.1%. However, most of these symptoms are mild. Clinically significant acid related complications such as bleeding, ulcerations, structure and fistulization have been reported. Although rare, dysplastic changes and malignancies in association with HGMPE have also been reported. Associations with Barrett’s esophagus have also been reported but the findings so far have been conflicting. There are still many areas that are unknown or not well understood and these include the natural history of HGMPE, risk factors for complications, role of Helicobacter pylori infection and factors associated with malignant transformations. Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes. Despite the overall low incidence of clinically relevant manifestations reported in the literature, HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance. PMID:23372354

Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development.

PubMed

Nguyen, Thao M; Arthur, Agnieszka; Paton, Sharon; Hemming, Sarah; Panagopoulos, Romana; Codrington, John; Walkley, Carl R; Zannettino, Andrew C W; Gronthos, Stan

2016-12-01

The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1 fl/fl ) in osteogenic progenitor cells, under the control of the osterix (Osx:Cre) promoter. The Osx:EfnB1 -/- mice displayed aberrant bone growth during embryonic and postnatal skeletal development up to 4weeks of age, when compared to the Osx:Cre controls. Furthermore, compared to the Osx:Cre control mice, the Osx:EfnB1 -/- mice exhibited significantly weaker and less rigid bones, with a reduction in trabecular/ cortical bone formation, reduced trabecular architecture and a reduction in the size of the growth plates at the distal end of the femora from newborn through to 4weeks of age. The aberrant bone formation correlated with increased numbers of tartrate resistant acid phosphatase positive osteoclasts and decreased numbers of bone lining osteoblasts in 4week old Osx:EfnB1 -/- mice, compared to Osx:Cre control mice. Taken together, these observations demonstrate the importance of ephrinB1 signalling between cells of the skeleton required for endochondral ossification. Copyright © 2016 Elsevier Inc. All rights reserved.

Ovarian tissue vitrification and heterotopic autologous transplantation in prepubertal Wistar rats.

PubMed

Wietcovsky, Leticia; Til, David; Salvador, Rafael Alonso; Amaral, Nicole Louise Lângaro; Senn, Alfred Paul; Amaral, Vera Lucia Lângaro

2018-03-15

To evaluate the efficiency of ovarian tissue heterotopic autografting after vitrification in prepubertal rats. Fragments of excised ovaries from prepubertal rats were used after assessing post-warming cellular viability, to determine the best vitrification protocol prior to retroauricular autografting. Pre-pubertal females (N=24) were castrated and divided into three group: Group 1 - fresh ovarian tissue transplantation; Group 2 - vitrified/warmed tissue transplantation; Group 3 - bilateral oophorectomy without transplantation. The ovarian fragments were exposed to solutions from the Ingamed® commercial kit, allocated in bacteriological loops and immersed in liquid nitrogen. Sixty days after transplantation, a vaginal mucus sample was collected for cytology tests, followed by sacrificing the animal, performing a cardiac puncture for collecting a blood sample to determine luteinizing hormone and estradiol levels, and excision of the transplanted fragment for histology tests. Vaginal cytology revealed that 87.5% of females from groups 1 and 2 had estrus while all females in Group 3 remained in diestrus. The mean LH value in groups 1 (0.08 mIU/mL) and 2 (0.34 mIU/mL) were statistically different from that of Group 3 (2.27 mIU/mL). E2 values did not differ between the groups. The histological analysis of Group 1 excised grafts versus those from Group 2 showed a higher percentage of primary follicles (62.5% vs. 12.5%), developing follicles (75% vs. 25%), corpus luteum (37.5% vs. 12.5%) and stromal region (100% vs. 87.5%). This study indicated that pre-pubertal ovarian tissue vitrification can be used to preserve fertility and to restore endocrine function in castrated rats.

Dwarfism and early death in mice lacking C-type natriuretic peptide

PubMed Central

Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

2001-01-01

Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone-related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor.

PubMed

Kong, Li; Zhao, Yun-Peng; Tian, Qing-Yun; Feng, Jian-Quan; Kobayashi, Tatsuya; Merregaert, Joseph; Liu, Chuan-Ju

2016-08-01

Chondrogenesis and endochondral ossification are precisely controlled by cellular interactions with surrounding matrix proteins and growth factors that mediate cellular signaling pathways. Here, we report that extracellular matrix protein 1 (ECM1) is a previously unrecognized regulator of chondrogenesis. ECM1 is induced in the course of chondrogenesis and its expression in chondrocytes strictly depends on parathyroid hormone-related peptide (PTHrP) signaling pathway. Overexpression of ECM1 suppresses, whereas suppression of ECM1 enhances, chondrocyte differentiation and hypertrophy in vitro and ex vivo In addition, target transgene of ECM1 in chondrocytes or osteoblasts in mice leads to striking defects in cartilage development and endochondral bone formation. Of importance, ECM1 seems to be critical for PTHrP action in chondrogenesis, as blockage of ECM1 nearly abolishes PTHrP regulation of chondrocyte hypertrophy, and overexpression of ECM1 rescues disorganized growth plates of PTHrP-null mice. Furthermore, ECM1 and progranulin chondrogenic growth factor constitute an interaction network and act in concert in the regulation of chondrogenesis.-Kong, L., Zhao, Y.-P., Tian, Q.-Y., Feng, J.-Q., Kobayashi, T., Merregaert, J., Liu, C.-J. Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone-related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor. © FASEB.

Mesenchymal Stem Cells Suppress Chronic Rejection in Heterotopic Small Intestine Transplant Rat Models Via Inhibition of CD68, Transforming Growth Factor- β1, and Platelet-Derived Growth Factor Expression.

PubMed

Li, Fuxin; Cao, Jisen; Zhao, Zhicheng; Li, Chuan; Qi, Feng; Liu, Tong

2017-04-01

Mesenchymal stem cells are easy to obtain and expand, with characteristics of low immunogenicity and strong tissue repair capacity. In this study, our aim was to investigate the role of mesenchymal stem cells in chronic immune rejection of heterotopic small intestine transplant in rats. After successfully constructing a rat chronic immune rejection model of heterotopic small intestine transplant, we infused mesenchymal stem cells into the animal recipients. We observed mesenchymal stem cell location in the recipients, recipient survival, pathology changes, and the expression of CD68, transforming growth factor β1, and platelet-derived growth factor C in the donor intestine. Mesenchymal stem cells inhibited the lymphocyte proliferation caused by concanavalin A in vitro. After stem cells were infused into recipients, they were mainly located in the donor intestine, as well as in the spleen and thymus. Recovery after transplant and pathology changes of the donor intestine in rats with stem cell infusion were better than in the control group; however, we observed no differences in survival time, accompanied by downregulated expression of CD68, transforming growth factor β1, and platelet-derived growth factor C. Mesenchymal stem cells, to a certain extent, could inhibit the process of chronic rejection. The mechanisms may include the inhibited function of these cells on lymphocyte proliferation, reduced infiltration of macrophages, and reduced expression of transforming growth factor β1 and platelet-derived growth factor C.

Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating the Distal Phalanx.

PubMed

Sheehy, Eamon J; Mesallati, Tariq; Kelly, Lara; Vinardell, Tatiana; Buckley, Conor T; Kelly, Daniel J

2015-01-01

Novel strategies are urgently required to facilitate regeneration of entire bones lost due to trauma or disease. In this study, we present a novel framework for the regeneration of whole bones by tissue engineering anatomically shaped hypertrophic cartilaginous grafts in vitro that subsequently drive endochondral bone formation in vivo. To realize this, we first fabricated molds from digitized images to generate mesenchymal stem cell-laden alginate hydrogels in the shape of different bones (the temporomandibular joint [TMJ] condyle and the distal phalanx). These constructs could be stimulated in vitro to generate anatomically shaped hypertrophic cartilaginous tissues that had begun to calcify around their periphery. Constructs were then formed into the shape of the distal phalanx to create the hypertrophic precursor of the osseous component of an engineered long bone. A layer of cartilage engineered through self-assembly of chondrocytes served as the articular surface of these constructs. Following chondrogenic priming and subcutaneous implantation, the hypertrophic phase of the engineered phalanx underwent endochondral ossification, leading to the generation of a vascularized bone integrated with a covering layer of stable articular cartilage. Furthermore, spatial bone deposition within the construct could be modulated by altering the architecture of the osseous component before implantation. These findings open up new horizons to whole limb regeneration by recapitulating key aspects of normal bone development.

Refractory pain following hip arthroscopy: evaluation and management

PubMed Central

de SA, Darren L; Burnham, Jeremy M; Mauro, Craig S

2018-01-01

ABSTRACT With increased knowledge and understanding of hip pathology, hip arthroscopy is rapidly becoming a popular treatment option for young patients with hip pain. Despite improved clinical and radiographic outcomes with arthroscopic treatment, some patients may have ongoing pain and less than satisfactory outcomes. While the reasons leading to failed hip arthroscopy are multifactorial, patient selection, surgical technique and rehabilitation all play a role. Patients with failed hip arthroscopy should undergo a thorough history and physical examination, as well as indicated imaging. A treatment plan should then be developed based on pertinent findings from the workup and in conjunction with the patient. Depending on the etiology of failed hip arthroscopy, management may be nonsurgical or surgical, which may include revision arthroscopic or open surgery, periacetabular osteotomy or joint arthroplasty. Revision surgery may be appropriate in settings including, but not limited to, incompletely treated femoroacetabular impingement, postoperative adhesions, heterotopic ossification, instability, hip dysplasia or advanced degeneration. PMID:29423245

Characterization of focal muscle compression under impact loading

NASA Astrophysics Data System (ADS)

Butler, B. J.; Sory, D. R.; Nguyen, T.-T. N.; Proud, W. G.; Williams, A.; Brown, K. A.

2017-01-01

In modern wars over 70% of combat wounds are to the extremities. These injuries are characterized by disruption and contamination of the limb soft tissue envelope. The extent of this tissue trauma and contamination determine the outcome of the extremity injury. In military injury, common post-traumatic complications at amputation sites include heterotopic ossification (formation of bone in soft tissue), and severe soft tissue and bone infections. We are currently developing a model of soft tissue injury that recreates pathologies observed in combat injuries. Here we present characterization of a controlled focal compression of the rabbit flexor carpi ulnaris (FCU) muscle group. The FCU was previously identified as a suitable site for studying impact injury because its muscle belly can easily be mobilized from the underlying bone without disturbing anatomical alignment in the limb. We show how macroscopic changes in tissue organization, as visualized using optical microscopy, can be correlated with data from temporally resolved traces of loading conditions.

Hypomorphic mutation in mouse Nppc gene causes retarded bone growth due to impaired endochondral ossification

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

Tsuji, Takehito; Kondo, Eri; Yasoda, Akihiro

2008-11-07

Long bone abnormality (lbab/lbab) is a spontaneous mutant mouse characterized by dwarfism with shorter long bones. A missense mutation was reported in the Nppc gene, which encodes C-type natriuretic peptide (CNP), but it has not been confirmed whether this mutation is responsible for the dwarf phenotype. To verify that the mutation causes the dwarfism of lbab/lbab mice, we first investigated the effect of CNP in lbab/lbab mice. By transgenic rescue with chondrocyte-specific expression of CNP, the dwarf phenotype in lbab/lbab mice was completely compensated. Next, we revealed that CNP derived from the lbab allele retained only slight activity to inducemore » cGMP production through its receptor. Histological analysis showed that both proliferative and hypertrophic zones of chondrocytes in the growth plate of lbab/lbab mice were markedly reduced. Our results demonstrate that lbab/lbab mice have a hypomorphic mutation in the Nppc gene that is responsible for dwarfism caused by impaired endochondral ossification.« less

An awake, minimally-invasive, fully-endoscopic surgical technique for treating lumbar radiculopathy secondary to heterotopic foraminal bone formation after a minimally invasive transforaminal lumbar interbody fusion with BMP: technical note

PubMed Central

2018-01-01

One complication associated with recombinant human bone morphogenetic protein (rhBMP-2) use in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is heterotopic bone growth at the neural foramen which results in the compression of neural structures. Here we present an awake, minimally invasive surgical approach for treating the radiculopathy that results from this excessive bone growth in the foramen. A 42-year-old male underwent a lumbar 4–sacral 1 MIS-TLIF by another surgeon. He did well in the initial postoperative period, but he began to note right leg pain and numbness in an L5 dermatomal pattern. The pain continued for 2 years despite interventional pain management, and he began to note left foot dorsiflexion weakness. An electromyography (EMG) showed a left L5 radiculopathy and a CT Lumbar spine demonstrated excessive bone growth in the right L4–5 neural foramen. The patient underwent an awake, endoscopic foraminotomy procedure utilizing a blunt tipped manual shaver drill system. The patient’s radicular symptoms improved immediately, and he remained asymptomatic at the 1 year follow up. Heterotopic foraminal bone growth is one potential complication of rhBMP-2 use in the MIS-TLIF procedure. The endoscopic procedure described here is a minimally invasive surgical option that can be performed in an awake patient and is suggested a unique salvage or rescue procedure to be considered for the treatment of this potential rhBMP-2 complication. PMID:29732437

Clinical outcomes of scala vestibuli cochlear implantation in children with partial labyrinthine ossification.

PubMed

Lin, Yung-Song

2009-03-01

Cochlear implantation via the scala vestibuli is a viable approach in those with ossification in the scala tympani. With extended cochlear implant experience, there is no significant difference in the mapping parameters and auditory performance between those implanted via scala vestibuli and via scala tympani. To assess the clinical outcomes of cochlear implantation via scala vestibuli. In a cohort follow-up study, 11 prelingually deafened children who received cochlear implantation between age 3 and 10 years through the scala vestibuli served as participants. The mapping parameters (i.e. comfortable level (C), threshold level (T), dynamic range) and auditory performance of each participant were evaluated following initial cochlear implant stimulation, then at 3 month intervals for 2 years, then semi-annually. The follow-up period lasted for 9 years 9 months on average, with a minimum of 8 years 3 months. The clinical results of the mapping parameters and auditory performance of children implanted via the scala vestibuli were comparative to those who were implanted via the scala tympani. No balance problem was reported by any of these patients. One child exhibited residual low frequency hearing after implantation.

Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone–related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor

PubMed Central

Kong, Li; Zhao, Yun-Peng; Tian, Qing-Yun; Feng, Jian-Quan; Kobayashi, Tatsuya; Merregaert, Joseph; Liu, Chuan-Ju

2016-01-01

Chondrogenesis and endochondral ossification are precisely controlled by cellular interactions with surrounding matrix proteins and growth factors that mediate cellular signaling pathways. Here, we report that extracellular matrix protein 1 (ECM1) is a previously unrecognized regulator of chondrogenesis. ECM1 is induced in the course of chondrogenesis and its expression in chondrocytes strictly depends on parathyroid hormone–related peptide (PTHrP) signaling pathway. Overexpression of ECM1 suppresses, whereas suppression of ECM1 enhances, chondrocyte differentiation and hypertrophy in vitro and ex vivo. In addition, target transgene of ECM1 in chondrocytes or osteoblasts in mice leads to striking defects in cartilage development and endochondral bone formation. Of importance, ECM1 seems to be critical for PTHrP action in chondrogenesis, as blockage of ECM1 nearly abolishes PTHrP regulation of chondrocyte hypertrophy, and overexpression of ECM1 rescues disorganized growth plates of PTHrP-null mice. Furthermore, ECM1 and progranulin chondrogenic growth factor constitute an interaction network and act in concert in the regulation of chondrogenesis.—Kong, L., Zhao, Y.-P., Tian, Q.-Y., Feng, J.-Q., Kobayashi, T., Merregaert, J., Liu, C.-J. Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone–related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor. PMID:27075243

Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration.

PubMed

Spalthoff, S; Jehn, P; Zimmerer, R; Möllmann, U; Gellrich, N-C; Kokemueller, H

2015-06-01

We previously generated viable heterotopic bone in living animals and found that 3 months of intrinsic vascularization improved bone formation and matrix degeneration. In this study, we varied the pre-vascularization time to determine its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm-long cylindrical β-tricalcium phosphate scaffolds were filled intraoperatively with autogenous iliac crest bone marrow and implanted in the latissimus dorsi muscle in six sheep. To examine the effect of axial perfusion, one scaffold was surgically implanted with (group C) or without (group D) a central vascular bundle. All animals were sacrificed 6 months postoperatively and histomorphometric measurements were compared to previous results. All implanted scaffolds exhibited ectopic bone growth. However, bone growth was not significantly different between the 3-month (group A, 0.191±0.097 vs. group C, 0.237±0.075; P=0.345) and 6-month (group B, 0.303±0.105 vs. group D, 0.365±0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early differences between surgically and extrinsically vascularized constructs disappeared after 6 months. Here, we describe a reliable procedure for generating ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient and ceramic degradation proceeds in accordance with bone generation, supporting the hypothesis of cell-mediated resorption. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: an experimental investigation in immature pigs.

PubMed

Kim, Harry K W; Aruwajoye, Olumide; Du, Justin; Kamiya, Nobuhiro

2014-09-17

Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease. Eighteen piglets were surgically induced with femoral head ischemia. Immediately following the surgery, all animals received an above-the-knee amputation to enforce local non-weight-bearing (NWB). One to two weeks later, six animals received local BMP-2 to the necrotic head (BMP group), six received local BMP-2 and ibandronate (BMP+IB group), and the remaining six received no treatment (NWB group). All animals were killed at eight weeks after the induction of ischemia. Radiographic, microcomputed tomography (micro-CT), and histomorphometric assessments were performed. Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP+IB groups had a decrease of 20%, 14%, and 10%, respectively, in their mean epiphyseal quotient in comparison with the normal control group. Micro-CT analyses showed significantly higher femoral head bone volume in the BMP+IB group than in the BMP group (p = 0.02) and the NWB group (p < 0.001). BMP+IB and BMP groups had a significantly higher trabecular number (p < 0.01) and lower trabecular separation (p < 0.02) than the NWB group. In addition, the osteoclast number per bone surface was significantly lower in the BMP+IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP+IB groups than in the NWB group (p < 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP+IB group but not in the BMP group. Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non

Cervical arthroplasty: a critical review of the literature.

PubMed

Alvin, Matthew D; Abbott, E Emily; Lubelski, Daniel; Kuhns, Benjamin; Nowacki, Amy S; Steinmetz, Michael P; Benzel, Edward C; Mroz, Thomas E

2014-09-01

ossification rate of 22%, whereas those studies with no COI (n=43) had a rate of 46%. Associated COIs did not influence QOL outcomes. Conflicts of interest were more likely to be present in studies published after 2008, and those with a COI reported greater adjacent segment disease rates for ACDF than CDA. In addition, heterotopic ossification rates were much lower in studies with COI versus those without COI. Thus, COIs did not affect QOL outcomes but were associated with lower complication rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Ossification of the posterior longitudinal ligament of the cervical spine in 3161 patients: a CT-based study.

PubMed

Fujimori, Takahito; Le, Hai; Hu, Serena S; Chin, Cynthia; Pekmezci, Murat; Schairer, William; Tay, Bobby K; Hamasaki, Toshimitsu; Yoshikawa, Hideki; Iwasaki, Motoki

2015-04-01

A cross-sectional study. To examine the prevalence of ossification of the posterior longitudinal ligament (OPLL) and ossification of the nuchal ligament (ONL) of the cervical spine in the San Francisco area. The prevalence of OPLL and ONL is unknown in the non-Asian population. This computed tomography-based cross-sectional study assessed the prevalence of OPLL and ONL within the cervical spine of patients treated at a level 1 trauma center between 2009 and 2012. The prevalence of both OPLL and ONL was compared between racial groups. Of the 3161 patients (mean age, 51.2 ± 21.6 yr; 66.1% male), there were 1593 Caucasians (50.4%), 624 Asians (19.7%), 472 Hispanics (14.9%), 326 African Americans (10.3%), 62 Native Americans (2.0%), and 84 Others (2.7%). The prevalence of cervical OPLL was 2.2% (95% confidence interval [CI]: 1.7-2.8). The adjusted prevalence was 1.3% in Caucasian Americans (95% CI: 0.7-2.3), 4.8% in Asian Americans (95% CI: 2.8-8.1), 1.9% in Hispanic Americans (95% CI: 0.9-4.0), 2.1% in African Americans (95% CI: 0.9-4.8), and 3.2% in Native Americans (95% CI: 0.8-12.3). The prevalence of OPLL in Asian Americans was significantly higher than that in Caucasian Americans (P = 0.005). ONL was detected in 346 patients and the prevalence was 10.9% (95% CI: 10.0-12.0). The adjusted prevalence of ONL was 7.3% in Caucasian Americans (95% CI: 5.8-9.3), 26.4% in Asian Americans (95% CI: 21.9-31.5), 7.4% in Hispanic Americans (95% CI: 5.2-10.5), 2.5% in African Americans (95% CI: 1.2-4.9), and 25.8% in Native Americans (95% CI: 16.5-37.5). ONL was significantly more common in Asian Americans than in Caucasian Americans, Hispanic Americans, and African Americans (P = 0.001). This study also demonstrated that OPLL and ONL were significantly more common in Asian Americans than in Caucasian Americans. 3.

Pathogenesis of myelopathy in patients with ossification of the posterior longitudinal ligament.

PubMed

Matsunaga, Shunji; Kukita, Makoto; Hayashi, Kyoji; Shinkura, Reiko; Koriyama, Chihaya; Sakou, Takashi; Komiya, Setsuro

2002-03-01

The goal of this study was to clarify the pathogenesis of myelopathy in patients with ossification of the posterior longitudinal ligament (OPLL) based on the relationship between static compression factors and dynamic factors. There was a total of 247 patients, including 167 patients who were conservatively followed for a mean of 11 years and 2 months and 80 patients who had myelopathy at initial consultation and underwent surgery. The changes in clinical symptoms associated with OPLL in the cervical spine were examined periodically. During the natural course of OPLL in the cervical spine, 37 (22%) of 167 patients developed or suffered aggravated spinal symptoms. All of the patients with a space available for the spinal cord (SAC) less than 6 mm suffered myelopathy, whereas the patients with an SAC diameter of 14 mm or greater did not. No correlation was found between the presence or absence of myelopathy in patients whose SAC diameter ranged from 6 mm to less than 14 mm. In patients with myelopathy whose minimal SAC diameter ranged from 6 mm to less than 14 mm, the range of motion of the cervical spine was significantly greater. These results indicate that pathological compression by the ossified ligament above a certain critical point may be the most significant factor in inducing myelopathy, whereas below that point dynamic factors may be largely involved in inducing myelopathy.

Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis.

PubMed

Yang, Chih-Yu; Chang, Zee-Fen; Chau, Yat-Pang; Chen, Ann; Lee, Oscar Kuang-Sheng; Yang, An-Hang

2015-11-01

Uremic patients are predisposed to atrophy of the alveolar bone and narrowing of the dental pulp chamber. Such pulp chamber changes have only been diagnosed radiologically; however, this has not been supported by any pathological evidence. We used a uremic rat model with secondary hyperparathyroidism induced by 5/6 nephrectomy surgery and high-phosphate diet to examine the dental pulp and adjacent alveolar bone pathology. In addition, we collected pulp tissues for real-time PCR. We found an opposite histopathological presentation of the ossified dental pulp and the osteomalacic adjacent alveolar bone. Furthermore, pulp cells with positive staining for Thy-1, a surrogate stem cell marker, were significantly reduced in the pulp of uremic rats compared to the controls, indicating a paucity of stem cells. This was further evidenced by the reduced pulp expression of dickkopf-1 (Dkk-1), a Wnt/β-catenin signaling inhibitor produced by mesenchymal stem cells. In contrast, expressions of receptor activator of nuclear factor κB ligand (RANKL) and RANK in uremic pulp were up-regulated, probably to counteract the ossifying process of uremic pulp. In conclusion, uremic pulp ossifications were associated with a paucity of stem cells and dysregulated Dkk-1 and RANKL signaling systems, further shifting the imbalance toward osteogenesis. Strategies to counteract such an imbalance may offer a potential therapeutic target to improve dental health in uremic patients, which warrants further interventional studies.

Mitogen‐inducible gene‐6 partly mediates the inhibitory effects of prenatal dexamethasone exposure on endochondral ossification in long bones of fetal rats

PubMed Central

Shang‐Guan, Yangfan; Ma, Jing; Hu, Hang; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin

2016-01-01

Abstract Background and Purpose Prenatal exposure to dexamethasone slows down fetal linear growth and bone mineralization but the regulatory mechanism remains unknown. Here we assessed how dexamethasone regulates bone development in the fetus. Experimental Approach Dexamethasone (1 mg·kg−1·day−1) was injected subcutaneously every morning in pregnant rats from gestational day (GD)9 to GD20. Fetal femurs and tibias were harvested at GD20 for histological and gene expression analysis. Femurs of 12‐week‐old female offspring were harvested for microCT (μCT) measurement. Primary chondrocytes were treated with dexamethasone (10, 50, 250 and 1000 nM). Key Results Prenatal dexamethasone exposure resulted in accumulation of hypertrophic chondrocytes and delayed formation of the primary ossification centre in fetal long bone. The retardation was accompanied by reduced maturation of hypertrophic chondrocytes, decreased osteoclast number and down‐regulated expression of osteocalcin and bone sialoprotein in long bone. In addition, the mitogen‐inducible gene‐6 (Mig6) and osteoprotegerin (OPG) expression were stimulated, and the receptor activator of NF‐κB ligand (RANKL) expression was repressed. Moreover, dexamethasone activated OPG and repressed RANKL expression in both primary chondrocytes and primary osteoblasts, and the knockdown of Mig6 abolished the effect of dexamethasone on OPG expression. Further, μCT measurement showed loss of bone mass in femur of 12‐week‐old offspring with prenatal dexamethasone exposure. Conclusions and Implications Prenatal dexamethasone exposure delays endochondral ossification by suppressing chondrocyte maturation and osteoclast differentiation, which may be partly mediated by Mig6 activation in bone. Bone development retardation in the fetus may be associated with reduced bone mass in later life. PMID:27128203

Comparative Postembryonic Skeletal Ontogeny in Two Sister Lineages of Old World Tree Frogs (Rhacophoridae: Taruga, Polypedates)

PubMed Central

Senevirathne, Gayani; Kerney, Ryan

2017-01-01

Rhacophoridae, a family of morphologically cryptic frogs, with many genetically distinct evolutionary lineages, is understudied with respect to skeletal morphology, life history traits and skeletal ontogeny. Here we analyze two species each from two sister lineages, Taruga and Polypedates, and compare their postembryonic skeletal ontogeny, larval chondrocrania and adult osteology in the context of a well-resolved phylogeny. We further compare these ontogenetic traits with the direct-developing Pseudophilautus silus. For each species, we differentially stained a nearly complete developmental series of tadpoles from early postembryonic stages through metamorphosis to determine the intraspecific and interspecific differences of cranial and postcranial bones. Chondrocrania of the four species differ in 1) size; 2) presence/absence of anterolateral and posterior process; and 3) shape of the suprarostral cartilages. Interspecific variation of ossification sequences is limited during early stages, but conspicuous during later development. Early cranial ossification is typical of other anuran larvae, where the frontoparietal, exoccipital and parasphenoid ossify first. The ossification sequences of the cranial bones vary considerably within the four species. Both species of Taruga show a faster cranial ossification rate than Polypedates. Seven cranial bones form when larvae near metamorphic climax. Ossification of all 18 cranial bones is initiated by larval Gosner stage 46 in T. eques. However, some cranial bone formation is not initiated until after metamorphosis in the other three species. Postcranial sequence does not vary significantly. The comparison of adult osteology highlights two characters, which have not been previously recorded: presence/absence of the parieto-squamosal plates and bifurcated base of the omosternum. This study will provide a starting point for comparative analyses of rhacophorid skeletal ontogeny and facilitate the study of the evolution of

Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the hyaline cartilage and endochondral ossification and beta-catenin, Sox9, and osteocalcin immunostaining of 22 cases.

PubMed

Fanburg-Smith, Julie C; Auerbach, Aaron; Marwaha, Jayson S; Wang, Zengfeng; Rushing, Elisabeth J

2010-05-01

Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage tumor, is most commonly intraosseous but can occur in extraskeletal sites. We intensively observed the morphology and applied Sox9 (master regulator of chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for osteoblastic phenotype) to 22 central nervous system and musculoskeletal mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved and reviewed from our files. Immunohistochemistry and follow-up were obtained on mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal chondrosarcomas included 5 central nervous system (all female; mean age, 30.2; mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17 musculoskeletal (female-male ratio, 11:6; mean age, 31.1; mean size, 6.2 cm; 3 each of humerus and vertebrae; 2 each of pelvis, rib, tibia, neck soft tissue; one each of femur, unspecified bone, and elbow soft tissue). The hyaline cartilage in most tumors revealed a consistent linear progression of chondrocyte morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty-seven percent of cases demonstrated cell death and acquired osteoblastic phenotype, cells positive for osteocalcin at the site of endochondral ossification. Small round cells of mesenchymal chondrosarcoma were negative for osteocalcin. SOX9 was positive in both components of 21 of 22 cases of mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface between round cells and hyaline cartilage in 35% cases. Control skull and central nervous system cases were compared, including chondrosarcomas and small cell osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal chondrosarcoma demonstrates centrally located hyaline cartilage with a linear progression of chondrocytes from resting to proliferative to hypertrophic

Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall Transplantation

PubMed Central

Oh, Byoungchol; Furtmüller, Georg J.; Malek, Veronika; Fryer, Madeline L.; Brayton, Cory; Walczak, Piotr; Janowski, Miroslaw

2017-01-01

Background: Congenital and acquired chest wall deformities represent a significant challenge to functional reconstruction and may impact feasibility of heart transplantation for patients with end-stage organ failure. In the recent past, the concept of replacing like-with-like tissue by using vascularized composite allografts (VCA) has been enthusiastically employed for reconstruction of complex tissue defects. Methods: In this study, we introduce a novel murine model for en bloc chest wall, heart, and thymus transplantation and thereby the use of complex tissue allografts for reconstruction of both chest wall defects and also end-stage organ failure. Additionally, this model allows us to study the features of combined vascularized bone marrow (VBM), thymus, and heart transplantation on allograft survival and function. Heterotopic chest wall, thymus, and heart transplants were performed in untreated syngeneic and allogeneic combinations and in allogeneic combinations treated with costimulation blockade (CTLA4-Ig and MR-1). Results: Indefinite (ie, 150 d, N = 3) graft survival was observed in syngeneic controls. In untreated recipients of allogeneic grafts, the skin component was rejected after 10 (±1) days, whereas rejection of the heart occurred after 13 (± 1) days (N = 3). Costimulation blockade treatment prolonged survival of the heart and chest wall component (130 d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism (average: 2.35 ± 1.44%), whereas interestingly, the skin component was rejected after 13 (±1) days. Conclusion: Thus, this novel microsurgical model of VCA combined with solid organ transplantation is technically feasible and results in split tolerance when treated with costimulatory blockade. PMID:29632774

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation.

PubMed

Faure, Alice; Bruzzese, Laurie; Steinberg, Jean-Guillaume; Jammes, Yves; Torrents, Julia; Berdah, Stephane V; Garnier, Emmanuelle; Legris, Tristan; Loundou, Anderson; Chalopin, Matthieu; Magalon, Guy; Guieu, Regis; Fenouillet, Emmanuel; Lechevallier, Eric

2016-02-04

In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death

Malignant transformation of thymoma in recipient rats by heterotopic thymus transplantation from HTLV-I transgenic rats.

PubMed

Tsuji, Takahiro; Ikeda, Hitoshi; Tsuchikawa, Takahiro; Kikuchi, Kazunori; Baba, Tomohisa; Ishizu, Akihiro; Yoshiki, Takashi

2005-07-01

Transgenic rats expressing the pX gene of human T lymphocyte virus type-I (HTLV-I) under control of the rat lymphocyte-specific protein tyrosine kinase type-I promoter (lck-pX rats) developed benign epithelial thymomas. When the thymuses of newborn lck-pX rats were transplanted into the subcapsular space of the kidney in other thymectomized lck-pX rats, similar tumors developed in the transplanted thymuses. Following the tumor growth, dissemination in the abdominal cavity and distant metastasis occurred. The tumors were histopathologically similar to the original thymomas, but prominent nuclear atypia and high mitotic activity were present. The Ki-67 index was twice as high as that in the originals. The tumors were transplantable into the subcutis of lck-pX rats, although transplantation of the originals never succeeded. All evidence indicated that malignant transformation of thymoma was induced by the heterotopic transplantation. Expression of the pX transgene in the transformed tumors were significantly reduced. Among host genes, the expression of p16ink4a/ARF, which was significantly upregulated in the originals, was never detected in the transformed tumors. Genomic Southern blots and PCR suggest that homozygous deletion of the p16ink4a/ARF gene may play important roles in malignant transformation in this model. Our model described here is a useful unique model for in vivo malignant transformation.

Bone union and remodelling of the non-ossified segment in thoracic ossification of the posterior longitudinal ligament after posterior decompression and fusion surgery.

PubMed

Koda, Masao; Furuya, Takeo; Okawa, Akihiko; Aramomi, Masaaki; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Ikeda, Osamu; Takahashi, Kazuhisa; Mannoji, Chikato; Yamazaki, Masashi

2015-11-01

The motion at the non-ossified segment of the ossification of the posterior longitudinal ligament (OPLL) is thought to be highly correlated to aggravation of symptoms of myelopathy. The rationale for posterior decompression with instrumented fusion (PDF) surgery is to limit the motion of the non-ossified segment of OPLL by stabilization. The purpose of the present study was to elucidate the course of bone union and remodelling of the non-ossified segment of thoracic OPLL (T-OPLL) after PDF surgery. A total of 29 patients who underwent PDF surgery for T-OPLL were included in this study. We measured the thickness of the OPLLs by determining the thickest part of the OPLL in the sagittal multi-planer reconstruction CT images pre- and post-operatively. Five experienced spine surgeons independently performed CT measurements of OPLL thickness twice. Japanese Orthopaedic Association score for thoracic myelopathy was measured as clinical outcome measure. Non-ossified segment of OPLLs fused in 24 out of 29 (82.8 %) patients. The average thickness of the OPLL at its thickest segment was 8.0 mm and decreased to 7.3 mm at final follow-up. The decrease in ossification thickness was significantly larger in the patients who showed fusion of non-ossified segments of OPLL compared with that in the patients did not show fusion. There was no significant correlation between the clinical outcome and the decrease in thickness of the OPLLs. The results of this study showed that remodelling of the OPLLs, following fusion of non-ossified segment of OPLLs, resulted in a decreased OPLL thickness, with potential for a reduction of spinal cord compression.

3D printed microchannel networks to direct vascularisation during endochondral bone repair.

PubMed

Daly, Andrew C; Pitacco, Pierluca; Nulty, Jessica; Cunniffe, Gráinne M; Kelly, Daniel J

2018-04-01

Bone tissue engineering strategies that recapitulate the developmental process of endochondral ossification offer a promising route to bone repair. Clinical translation of such endochondral tissue engineering strategies will require overcoming a number of challenges, including the engineering of large and often anatomically complex cartilage grafts, as well as the persistence of core regions of avascular cartilage following their implantation into large bone defects. Here 3D printing technology is utilized to develop a versatile and scalable approach to guide vascularisation during endochondral bone repair. First, a sacrificial pluronic ink was used to 3D print interconnected microchannel networks in a mesenchymal stem cell (MSC) laden gelatin-methacryloyl (GelMA) hydrogel. These constructs (with and without microchannels) were next chondrogenically primed in vitro and then implanted into critically sized femoral bone defects in rats. The solid and microchanneled cartilage templates enhanced bone repair compared to untreated controls, with the solid cartilage templates (without microchannels) supporting the highest levels of total bone formation. However, the inclusion of 3D printed microchannels was found to promote osteoclast/immune cell invasion, hydrogel degradation, and vascularisation following implantation. In addition, the endochondral bone tissue engineering strategy was found to support comparable levels of bone healing to BMP-2 delivery, whilst promoting lower levels of heterotopic bone formation, with the microchanneled templates supporting the lowest levels of heterotopic bone formation. Taken together, these results demonstrate that 3D printed hypertrophic cartilage grafts represent a promising approach for the repair of complex bone fractures, particularly for larger defects where vascularisation will be a key challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparison of 2 heterotopic heart transplant techniques in rats: cervical and abdominal heart.

PubMed

Ma, Yi; Wang, Guodong

2011-04-01

Heterotopic heart transplant in rats has been accepted as the most commonly used animal model to investigate the mechanisms of transplant immunology. Many ingenious approaches to this model have been reported. We sought to improve this model and compare survival rates and histologic features of acute rejection in cervical and abdominal heart transplants. Rats were divided into cervical and abdominal groups. Microsurgical techniques were introduced for vascular anastomoses. In the abdominal heart transplant group, the donor's thoracic aorta was anastomosed end-to-side to the recipient's infrarenal abdominal aorta, and the donor's pulmonary artery was anastomosed to the recipient's inferior vena cava. In the cervical heart transplant group, the donor's thoracic aorta was anastomosed to the recipient's common carotid artery, and the donor's pulmonary artery was anastomosed to the recipient's external jugular vein. Survival time of the 2 models was followed and pathology was examined. Histologic features of allogeneic rejection also were compared in the cervical and abdominal heart transplant groups. The mean time to recover the donor's hearts was 7.4 ± 2.2 minutes in the cervical group and 7.2 ± 1.8 minutes in the abdominal group. In the cervical and abdominal heart transplant models, the mean recipient's operative time was 23.2 ± 2.6 minutes and 21.6 ± 2.8 minutes. Graft survival was 98% and 100% in the cervical and abdominal heart transplant groups. There was no significant difference in graft survival between the 2 methods. Heart allografts rejected at 5.7 and 6.2 days in the cervical and abdominal transplant groups. There was no difference in the histologic features of acute allogenic rejection in cervical and abdominal heart transplant. Both cervical and abdominal heart transplants can achieve a high rate of success. The histologic features of acute allogeneic rejection in the models are comparable.

Follow-up Findings in a Turkish Girl with Pseudohypoparathyroidism Type Ia Caused by a Novel Heterozygous Mutation in the GNAS Gene.

PubMed

Şahin, Sezgin; Hiort, Olaf; Thiele, Susanne; Evliyaoğlu, Olcay; Tüysüz, Beyhan

2017-03-01

Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by multihormone resistance and an Albright hereditary osteodystrophy (AHO) phenotype. It is caused by heterozygous mutations in GNAS gene. Clinical and biochemical findings of a female PHP-Ia patient were evaluated from age of diagnosis (6.5 years) to 14.5 years of age. The patient had short stature, brachydactyly, and subcutaneous heterotopic ossifications. Serum calcium and phosphorus levels were normal, but parathyroid hormone levels were high. Based on the typical clinical findings of AHO phenotype and biochemical findings, she was diagnosed as having PHP-Ia. A novel heterozygous mutation (c.128T>C) was found in the GNAS gene. Follow-up examinations revealed resistance to thyroid-stimulating hormone and a bioinactive growth hormone. Clinicians should take into consideration PHP-Ia in patients referred with short stature, and patients with an AHO phenotype must be further evaluated for hormone resistance, GNAS gene mutation, Gsα activity. To our knowledge, this is the first case report describing bioinactive growth hormone in PHP-Ia.

Characterization of Focal Muscle Compression Under Impact Loading

NASA Astrophysics Data System (ADS)

Butler, Ben; Sory, David; Nguyen, Thuy-Tien; Curry, Richard; Clasper, Jon; Proud, William; Williams, Alun; Brown, Kate

2015-06-01

The pattern of battle injuries sustained in modern wars shows that over 70% of combat wounds are to the extremities. These injuries are characterized by disruption and contamination of the limb soft tissue envelope. The extent of this tissue trauma and contamination determine the outcome in extremity injury. In military injury, common post-traumatic complications at amputation sites include heterotopic ossification (formation of bone in soft tissue), and severe soft tissue and bone infections. We are currently developing a model of soft tissue injury that recreates pathologies observed in combat injuries. Here we present characterization of a controlled focal compression of the rabbit flexor carpi ulnaris (FCU) muscle group. The FCU was previously identified as a suitable site for studying impact injury because its muscle belly can easily be mobilized from the underlying bone without disturbing anatomical alignment in the limb. We show how macroscopic changes in tissue organization, as visualized using optical microscopy, can be correlated with data from temporally resolved traces of loading conditions. Funding provided by the Royal British Legion.

Acute and chronic rapamycin use in patients with Fibrodysplasia Ossificans Progressiva: A report of two cases.

PubMed

Kaplan, Frederick S; Zeitlin, Leonid; Dunn, Stephen P; Benor, Shira; Hagin, David; Al Mukaddam, Mona; Pignolo, Robert J

2018-04-01

Fibrodysplasia Ossificans Progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification for which there is presently no definitive treatment. Several recent studies in genetic mouse models of FOP support involvement of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the pathophysiology of FOP and propose the repurposed use of rapamycin, an inhibitor of mTORC1 signaling in clinical trials for the management of FOP. Here we report two patients with the classic FOP mutation who received rapamycin-one for four months on a compassionate basis for treatment of acute flare-ups of the neck and back that were refractory to corticosteroid therapy-and the other for 18years for chronic immunosuppression following liver transplantation for intercurrent cytomegalovirus infection. In both patients, FOP progressed despite the use of rapamycin. This report highlights the real-world use of rapamycin in two FOP patients and provides insight into the use of rapamycin in clinical trials for the management of FOP. Copyright © 2017 Elsevier Inc. All rights reserved.

[Analysis of the results of total cervical disc arthroplasty using a M6-C prosthesis: a multicenter study].

PubMed

Byval'tsev, V A; Kalinin, A A; Stepanov, I A; Pestryakov, Yu Ya; Shepelev, V V

Cervical spondylosis and intervertebral disc (IVD) degeneration are the most common cause for compression of the spinal cord and/or its roots. Total IVD arthroplasty, as a modern alternative to surgical treatment of IVD degeneration, is gaining popularity in many neurosurgical clinics around the world. Aim - the study aim was to conduct a multicenter analysis of cervical spine arthroplasty with an IVD prosthesis M6-C ('Spinal Kinetics', USA). The study included 112 patients (77 males and 35 females). All patients underwent single-level discectomy with implantation of the artificial IVD prosthesis M6-C. The follow-up period was up to 36 months. Dynamic assessment of the prosthesis was based on clinical parameters (pain intensity in the cervical spine and upper extremities (visual analog scale - VAS); quality of life (Neck Disability Index - NDI)); and subjective satisfaction with the results of surgical treatment (Macnab scale) and instrumental data (range of motion in the operated spinal motion segment, degree of heterotopic ossification (McAfee-Suchomel classification), and time course of degenerative changes in the adjacent segments).

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

PubMed Central

Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

2017-01-01

The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

Skull Development, Ossification Pattern, and Adult Shape in the Emerging Lizard Model Organism Pogona vitticeps: A Comparative Analysis With Other Squamates.

PubMed

Ollonen, Joni; Da Silva, Filipe O; Mahlow, Kristin; Di-Poï, Nicolas

2018-01-01

skull shape of P. vitticeps and further indicates that heterochrony has played a key role in the early development and ossification of squamate skull bones. Such detailed studies of embryonic character development, craniofacial patterning, and bone formation are essential for the establishment of well-selected squamate species as Evo-Devo model organisms. We expect that P. vitticeps will continue to emerge as a new attractive model organism for understanding developmental and molecular processes underlying tissue formation, morphology, and evolution.

Skull Development, Ossification Pattern, and Adult Shape in the Emerging Lizard Model Organism Pogona vitticeps: A Comparative Analysis With Other Squamates

PubMed Central

Ollonen, Joni; Da Silva, Filipe O.; Mahlow, Kristin; Di-Poï, Nicolas

2018-01-01

skull shape of P. vitticeps and further indicates that heterochrony has played a key role in the early development and ossification of squamate skull bones. Such detailed studies of embryonic character development, craniofacial patterning, and bone formation are essential for the establishment of well-selected squamate species as Evo-Devo model organisms. We expect that P. vitticeps will continue to emerge as a new attractive model organism for understanding developmental and molecular processes underlying tissue formation, morphology, and evolution. PMID:29643813

Rupture of the distal biceps brachii tendon: conservative treatment versus anatomic reinsertion--clinical and radiological evaluation after 2 years.

PubMed

Chillemi, Claudio; Marinelli, Mario; De Cupis, Vincenzo

2007-10-01

Distal biceps tendon rupture is a relatively rare injury. It commonly occurs in the dominant extremity of middle-aged men during an excessive eccentric tension as the arm is forced from a flexed position, while it is rarely observed during sport activities. Many techniques, including non-operative and surgical option, have been described for the treatment of a ruptured distal biceps tendon, but there is still considerable controversy about the management of choice. Nine patients affected with traumatic distal tendon ruptures of the biceps brachii were followed-up for a minimum of 24 months. Five patients underwent surgery (two-incision technique) and four patients were treated conservatively. Tendon readaptation to its origin was done by a suture metal anchor. Outcome was evaluated based on the physical examination, radiographic analysis and the SECEC elbow score. The SECEC elbow score results show that every single item result is in favour of surgical treatment. On measurements of motion, we found a slight flexion-extension deficit in two patients, but reduced supination in six patients and reduced pronation in four. Two patients had postoperative dysfunction of the deep branch of the radial nerve. Radiographic examination showed heterotopic bone formation on the radial tuberosity around the presumed insertion of the reattached tendon in 2 of 5 patients and ectopic ossification more proximally in the area of the biceps muscle Our findings confirm the view that anatomic repair of distal biceps tendon rupture provides consistently good results and early anatomic reconstruction can restore strength and endurance for the elbow.

The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat

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

Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.

1990-12-01

To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease inmore » bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation.« less

Validation of the ultrasonographic assessment of the femoral trochlea epiphyseal cartilage in foals at osteochondrosis predilected sites with magnetic resonance imaging and histology.

PubMed

Martel, G; Forget, C; Gilbert, G; Richard, H; Moser, T; Olive, J; Laverty, S

2017-11-01

Noninvasive imaging tools are needed to screen foal femoropatellar joints to detect subclinical osteochondrosis lesions due to focal failure of endochondral ossification to enhance early management to optimise intrinsic healing events. Recently investigations employing 3T susceptibility-weighted magnetic resonance imaging (3T SWI MRI) and CT have demonstrated their capacity for early osteochondrosis diagnosis, but these technologies are not practical for field screening. We postulate that ultrasonography is a valuable field tool for the detection of subclinical osteochondrosis lesions. The goals were to 1) describe the ultrasonographic features of the femoral trochlea of healthy and osteochondrosis-predisposed neonatal foals, 2) validate the capacity of ultrasound to assess cartilage canal vascular archictecture and the ossification front and 3) evaluate field feasibility in a pilot study. Experimental study. Ultrasonographic evaluation of osteochondrosis predisposed (n = 10) and control (n = 6) femoral trochleas was performed ex vivo and compared with site-matched histological sections and 3T SWI MRI. The articular and epiphyseal cartilage thickness, ossification front indentation and cartilage canal vascular archictecture were assessed at each ROI. Femoral trochleae of foals (n = 3) aged ≈ 1, 3 and 6 months were also evaluated with ultrasonography in field. Ultrasonographic measurements strongly correlated with the histological measurements. There was no difference in the cartilage thickness or ossification front indentation between control and osteochondrosis-predisposed specimens. The cartilage canal vascular archictecture on ultrasonograms corresponded with the vessel pattern observed on site matched histology and 3T SWI MRI. The number of specimens for study was limited and no early osteochondrosis lesions were present within the predilected group, but a field study is now underway. Ultrasonographic examination of the femoral trochlea permitted accurate

Stabilization with the Dynamic Cervical Implant: a novel treatment approach following cervical discectomy and decompression.

PubMed

Matgé, Guy; Berthold, Christophe; Gunness, Vimal Raj Nitish; Hana, Ardian; Hertel, Frank

2015-03-01

57%, reduced motion (2°-5°) in 34.5%, and little motion (0-2°) in 8.5%. The Cobb and FSU angles improved, showing a clear tendency for lordosis with the DCI. Motion greater than 2° of the treated segment could be preserved in 91.5%, while 8.5% had a near segmental fusion. Mean ROM at index levels demonstrated satisfying motion preservation with DCI. Mean ROM at upper and lower adjacent levels showed maintenance of adjacent-level kinematics. Heterotopic ossification, including 20% minor and 15% major, had no direct impact on clinical results. There were 2 endplate subsidences detected with an increased segmental lordosis. One asymptomatic anterior device migration required reoperation. Three patients underwent a secondary surgery in another segment during follow-up, twice for a new disc herniation and once for an adjacent degeneration. There was no posterior migration and no device breakage. Preliminary results indicate that the DCI implanted using a proper surgical technique is safe and facilitates excellent clinical outcomes, maintains index-and adjacent-level ROM in the majority of cases, improves sagittal alignment, and may be suitable for patients with facet arthrosis who would otherwise not be candidates for cervical TDR. Shock absorption together with maintained motion in the DCI may protect adjacent levels from early degeneration in longer follow-up.

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

PubMed Central

Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

2011-01-01

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

PubMed

Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

2011-10-01

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

Thumb Ossification Composite Index (TOCI) for Predicting Peripubertal Skeletal Maturity and Peak Height Velocity in Idiopathic Scoliosis

PubMed Central

Hung, Alec L.H.; Chau, W.W.; Shi, B.; Chow, Simon K.; Yu, Fiona Y.P.; Lam, T.P.; Ng, Bobby K.W.; Qiu, Y.; Cheng, Jack C.Y.

2017-01-01

Background: Accurate skeletal maturity assessment is important to guide clinical evaluation of idiopathic scoliosis, but commonly used methods are inadequate or too complex for rapid clinical use. The objective of the study was to propose a new simplified staging method, called the thumb ossification composite index (TOCI), based on the ossification pattern of the 2 thumb epiphyses and the adductor sesamoid bone; to determine its accuracy in predicting skeletal maturation when compared with the Sanders simplified skeletal maturity system (SSMS); and to validate its interrater and intrarater reliability. Methods: Hand radiographs of 125 girls, acquired when they were newly diagnosed with idiopathic scoliosis prior to menarche and during longitudinal follow-up until skeletal maturity (a minimum of 4 years), were scored with the TOCI and SSMS. These scores were compared with digital skeletal age (DSA) and radius, ulna, and small hand bones (RUS) scores; anthropometric data; peak height velocity; and growth-remaining profiles. Correlations were analyzed with the chi-square test, Spearman and Cramer V correlation methods, and receiver operating characteristic curve analysis. Reliability analysis using the intraclass correlation (ICC) was conducted. Results: Six hundred and forty-five hand radiographs (average, 5 of each girl) were scored. The TOCI staging system was highly correlated with the DSA and RUS scores (r = 0.93 and 0.92, p < 0.01). The mean peak height velocity (and standard deviation) was 7.43 ± 1.45 cm/yr and occurred at a mean age of 11.9 ± 0.86 years, with 70.1% and 51.4% of the subjects attaining their peak height velocity at TOCI stage 5 and SSMS stage 3, respectively. The 2 systems predicted peak height velocity with comparable accuracy, with a strong Cramer V association (0.526 and 0.466, respectively; p < 0.01) and similar sensitivity and specificity on receiver operating characteristic curve analysis. The mean age at menarche was 12.57 ± 1

A new hynobiid-like salamander (Amphibia, Urodela) from Inner Mongolia, China, provides a rare case study of developmental features in an Early Cretaceous fossil urodele

PubMed Central

Jia, Jia

2016-01-01

A new fossil salamander, Nuominerpeton aquilonaris (gen. et sp. nov.), is named and described based on specimens from the Lower Cretaceous Guanghua Formation of Inner Mongolia, China. The new discovery documents a far northern occurrence of Early Cretaceous salamanders in China, extending the geographic distribution for the Mesozoic fossil record of the group from the Jehol area (40th–45th parallel north) to near the 49th parallel north. The new salamander is characterized by having the orbitosphenoid semicircular in shape; coracoid plate of the scapulocoracoid greatly expanded with a convex ventral and posterior border; ossification of two centralia in carpus and tarsus; and first digit being about half the length of the second digit in both manus and pes. The new salamander appears to be closely related to hynobiids, although this inferred relationship awaits confirmation by research in progress by us on a morphological and molecular combined analysis of cryptobranchoid relationships. Comparison of adult with larval and postmetamorphic juvenile specimens provides insights into developmental patterns of cranial and postcranial skeletons in this fossil species, especially resorption of the palatine and anterior portions of the palatopterygoid in the palate and the coronoid in the mandible during metamorphosis, and postmetamorphic ossification of the mesopodium in both manus and pes. Thus, this study provides a rare case study of developmental features in a Mesozoic salamander. PMID:27761316

What Is It Like to Be a Child? Childhood Subjectivity and Teacher Memories as Heterotopia

ERIC Educational Resources Information Center

Chang-Kredl, Sandra; Wilkie, Gala

2016-01-01

Foucault's notion of heterotopia offers a novel way to understand teachers' conceptualizations of childhood, in juxtaposing adult memories of childhood with their present context of teaching children. Memory writing prompts were given to 41 early childhood teachers, and the resulting written narratives were analyzed as heterotopic spaces. The…

Apixaban Versus Warfarin for Mechanical Heart Valve Thromboprophylaxis in a Swine Aortic Heterotopic Valve Model.

PubMed

Lester, Patrick A; Coleman, Dawn M; Diaz, Jose A; Jackson, Tatum O; Hawley, Angela E; Mathues, Angela R; Grant, Brandon T; Knabb, Robert M; Ramacciotti, Eduardo; Frost, Charles E; Song, Yan; Wakefield, Thomas W; Myers, Daniel D

2017-05-01

Warfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy. A well-documented heterotopic aortic valve porcine model was used to test the hypothesis that apixaban has comparable efficacy to warfarin for thromboprophylaxis of mechanical heart valves. Sixteen swine were implanted with a bileaflet mechanical aortic valve that bypassed the ligated descending thoracic aorta. Animals were randomized to 4 groups: control (no anticoagulation; n=4), apixaban oral 1 mg/kg twice a day (n=5), warfarin oral 0.04 to 0.08 mg/kg daily (international normalized ratio 2-3; n=3), and apixaban infusion (n=4). Postmortem valve thrombus was measured 30 days post-surgery for control-oral groups and 14 days post-surgery for the apixaban infusion group. Control thrombus weight (mean) was significantly different (1422.9 mg) compared with apixaban oral (357.5 mg), warfarin (247.1 mg), and apixiban 14-day infusion (61.1 mg; P <0.05). Apixaban is a promising candidate and may be a useful alternative to warfarin for thromboprophylaxis of mechanical heart valves. Unlike warfarin, no adverse bleeding events were observed in any apixaban groups. © 2017 American Heart Association, Inc.

Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs.

PubMed

Fernández-Rodríguez, O M; Ríos, A; Navarro, J L; Pons, J A; Palenciano, C G; Mota, R; Berenguer, J J; Mulero, F; Contreras, J; Conesa, C; Ramírez, P; Fuente, T; Parrilla, P

2006-04-01

Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.

Cerebro-costo-mandibular syndrome in a father and a female fetus: early prenatal ultrasonographic diagnosis and autosomal dominant transmission.

PubMed

Morin, G; Gekas, J; Naepels, P; Gondry, J; Devauchelle, B; Testelin, S; Sevestre, H; Thépôt, F; Mathieu, M

2001-10-01

Ultrasonography in a female fetus revealed cystic cervical hygroma, severe micrognathia, and vertebral and upper limb anomalies suggestive of cerebro-costo-mandibular syndrome (CCMS) which was diagnosed ultrasonographically at 16 weeks' gestation. The father is affected and presents with a Pierre Robin sequence, short stature and typical costovertebral anomalies. CCMS is a rare and severe disorder. The high frequency of sporadic cases, vertical transmission, and the excess of sibs affected via horizontal transmission suggest dominant autosomal mutation with possible germinal mosaicism. The vertical familial case detailed in the present report is a reminder of the high risk when one parent or one sibling is affected and the extreme variability of phenotype and costal ossification. Early prenatal ultrasound diagnosis is possible in a severely affected fetus. Copyright 2001 John Wiley & Sons, Ltd.

Outcome of posterior decompression with instrumented fusion surgery for K-line (-) cervical ossification of the longitudinal ligament.

PubMed

Saito, Junya; Maki, Satoshi; Kamiya, Koshiro; Furuya, Takeo; Inada, Taigo; Ota, Mitsutoshi; Iijima, Yasushi; Takahashi, Kazuhisa; Yamazaki, Masashi; Aramomi, Masaaki; Mannoji, Chikato; Koda, Masao

2016-10-01

We investigated the outcome of posterior decompression and instrumented fusion (PDF) surgery for patients with K-line (-) ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, who may have a poor surgical prognosis. We retrospectively analyzed the outcome of a series of 27 patients who underwent PDF without correction of cervical alignment for K-line (-) OPLL and were followed-up for at least 1 year after surgery. We had performed double-door laminoplasty followed by posterior instrumented fusion without excessive correction of cervical spine alignment. The preoperative Japanese Orthopedic Association (JOA) score for cervical myelopathy was 8.0 points and postoperative JOA score was 11.9 points on average. The mean JOA score recovery rate was 43.6%. The average C2-C7 angle was 2.2° preoperatively and 3.1° postoperatively. The average maximum occupation ratio of OPLL was 56.7%. In conclusion, PDF without correcting cervical alignment for patients with K-line (-) OPLL showed moderate neurological recovery, which was acceptable considering K-line (-) predicts poor surgical outcomes. Thus, PDF is a surgical option for such patients with OPLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiographic analysis of the correlation between ossification of the nuchal ligament and sagittal alignment and segmental stability of the cervical spine in patients with cervical spondylotic myelopathy.

PubMed

Ying, Jinwei; Teng, Honglin; Qian, Yunfan; Hu, Yingying; Wen, Tianyong; Ruan, Dike; Zhu, Minyu

2018-01-01

Background Ossification of the nuchal ligament (ONL) caused by chronic injury to the nuchal ligament (NL) is very common in instability-related cervical disorders. Purpose To determine possible correlations between ONL, sagittal alignment, and segmental stability of the cervical spine. Material and Methods Seventy-three patients with cervical spondylotic myelopathy (CSM) and ONL (ONL group) and 118 patients with CSM only (control group) were recruited. Radiographic data included the characteristics of ONL, sagittal alignment and segmental stability, and ossification of the posterior longitudinal ligament (OPLL). We performed comparisons in terms of radiographic parameters between the ONL and control groups. The correlations between ONL size, cervical sagittal alignment, and segmental stability were analyzed. Multivariate logistic regression was used to identify the independent risk factors of the development of ONL. Results C2-C7 sagittal vertical axis (SVA), T1 slope (T1S), T1S minus cervical lordosis (T1S-CL) on the lateral plain, angular displacement (AD), and horizontal displacement (HD) on the dynamic radiograph increased significantly in the ONL group compared with the control group. The size of ONL significantly correlated with C2-C7 SVA, T1S, AD, and HD. The incidence of ONL was higher in patients with OPLL and segmental instability. Cervical instability, sagittal malalignment, and OPLL were independent predictors of the development of ONL through multivariate analysis. Conclusion Patients with ONL are more likely to have abnormal sagittal alignment and instability of the cervical spine. Thus, increased awareness and appreciation of this often-overlooked radiographic finding is warranted during diagnosis and treatment of instability-related cervical pathologies and injuries.

Endoscopic excavation for gastric heterotopic pancreas: an analysis of 42 cases from a tertiary center.

PubMed

Zhang, Yu; Huang, Qin; Zhu, Lin-hong; Zhou, Xian-bin; Ye, Li-ping; Mao, Xin-li

2014-09-01

Because of the difficulty associated with making an accurate diagnosis of gastric heterotopic pancreas (HP) before surgery, surgical resection is usually performed in suspected cases. However, this is an invasive procedure and prone to certain surgical complications. This study was designed to evaluate the feasibility of endoscopic excavation for gastric HP, as well as the value of endoscopic ultrasonography (EUS) in diagnosing gastric HP. Between January 2007 and January 2013, 42 consecutive patients with gastric HP were enrolled in this retrospective study. Key steps: (1) Injection of a solution (100 ml saline + 2 ml indigo carmine + 1 ml epinephrine) into the submucosal layer after making several dots around the lesion; (2) Incision of the mucosa outside the marker dots with a needle-knife, and then circumferential excavation until complete resection of the lesion; (3) Closure of the artificial ulcer with several clips after tumor removal. In this study, 18 cases (42.9%) were suspected as gastric HP (assessed by two experienced endoscopists before endoscopic excavation), 8 (19.0%) were suspected as gastrointestinal stromal tumors, 7 (16.7%) as gastric polyp, and the remaining 9 cases (21.4%) were still unknown. The mean procedure duration was 28.6 min. En bloc resection by endoscopic excavation was achieved in 40 cases (95.2%), and no massive bleeding, delayed bleeding, perforation, or other severe complication occurred in these patients. Among the 42 lesions, a tube echo could be detected in 11 cases by EUS. Those 11 cases were diagnosed as gastric HP by histopathology. Endoscopic excavation appears to be a safe and feasible procedure for accurate histopathologic evaluation and curative treatment in gastric HP. Use of EUS has some value in the diagnosis of gastric HP before the procedure

[Treatment of type C intercondylar fractures of distal humerus using dual plating].

PubMed

Liu, Ya-Ke; Xu, Hua; Liu, Fan; Wang, You-Hua; Tao, Ran; Cao, Yi; Wang, Hong; Zhou, Zhen-Yu; Zhu, Yong

2009-06-15

To evaluate the clinical outcome of dual plating in the treatment of humeral intercondylar type-C fractures in adults. From June 2004 to October 2007, 38 cases of type-C distal humeral fractures were stabilised with dual plating. There were 21 males and 17 females. The average age was 43 years with a range from 21 to 71 years. According to the AO classification, 9 cases were of type C1, 17 of C2 and 12 of C3. The posterior midline approach was selected. Twenty-one cases were exposed through the trans-olecranon osteotomy, 11 through the Campbell (Van Gorder) approach, 6 through triceps sparing approach. Autogenous bone graft was performed in 5 cases because of severe comminution. Thirty-five patients were followed-up for 14-30 months (mean 24.2 months). At the latest follow-up, the elbow flexion averaged 119 degrees (range 90 degrees - 135 degrees ), and the loss of extension averaged 16.2 degrees (range 5 degrees - 25 degrees ). All the patients got bony healing, the average healing period was 14 weeks. The patients were evaluated using the criteria of Aitken and Rorabeek and the scores were 13 excellent, 16 good, 6 fair. Twenty-nine patients (82.9%) had a good or excellent results. Complications included 4 cases of traumatic osteoarthritis, 2 heterotopic ossification, 1 ulnar neuropathy. Infection as well as loosening or breakage of the implant was not found. The dual plating is able to provide rigid fixation for the humeral intercondylar fractures. In addition, it can allow early functional exercise after operation, decrease the related complications significantly, and improve the functional results.

Development of the Synarcual in the Elephant Sharks (Holocephali; Chondrichthyes): Implications for Vertebral Formation and Fusion.

PubMed

Johanson, Zerina; Boisvert, Catherine; Maksimenko, Anton; Currie, Peter; Trinajstic, Kate

2015-01-01

The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group 'Placodermi', in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the 'Placodermi', individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmentation and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disorders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callorhinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton. We

Development of the Synarcual in the Elephant Sharks (Holocephali; Chondrichthyes): Implications for Vertebral Formation and Fusion

PubMed Central

Johanson, Zerina; Boisvert, Catherine; Maksimenko, Anton; Currie, Peter; Trinajstic, Kate

2015-01-01

The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group ‘Placodermi’, in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the ‘Placodermi’, individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmentation and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disorders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callorhinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton

Stiffness after total knee arthroplasty.

PubMed

Manrique, Jorge; Gomez, Miguel M; Parvizi, Javad

2015-04-01

Stiffness after total knee arthroplasty (TKA) adversely affects outcome and impacts patient function. Various risk factors for stiffness after TKA have been identified, including reduced preoperative knee range of motion, history of prior knee surgery, etiology of arthritis, incorrect positioning or oversizing of components, and incorrect gap balancing. Mechanical and associated causes, such as infection, arthrofibrosis, complex regional pain syndrome, and heterotopic ossification, secondary gain issues have also been identified. Management of stiffness following TKA can be challenging. The condition needs to be assessed and treated in a staged manner. A nonsurgical approach is the first step. Manipulation under anesthesia may be considered within the first 3 months after the index TKA, if physical therapy fails to improve the range of motion. Beyond this point, consideration should be given to surgical intervention such as lysis of adhesions, either arthroscopically or by open arthrotomy. If the cause of stiffness is deemed to be surgical error, such as component malpositioning, revision arthroplasty is indicated. The purpose of this article is to evaluate the various aspects of management of stiffness after TKA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cervical artificial disc extrusion after a paragliding accident.

PubMed

Niu, Tianyi; Hoffman, Haydn; Lu, Daniel C

2017-01-01

Cervical total disc replacement (TDR) is an established alternative to anterior cervical discectomy and fusion (ACDF) with excellent long-term outcomes and low failure rates. Cases of implant failure and migration are scarce and primarily limited to several years postoperatively. The authors report a case of anterior extrusion of a C4-C5 ProDisc-C (DePuy Synthes, West Chester, PA, USA) cervical artificial disc (CAD) 14 months after placement due to minor trauma. A 33-year-old female who had undergone C4-C5 CAD implantation presented with neck pain and spasm after experiencing a paragliding accident. A 4 mm anterior protrusion of the CAD was seen on x-ray. She underwent removal of the CAD followed by anterior fusion. Other cases of CAD extrusion in the literature are discussed and the device's durability and testing are considered. Overall, CAD extrusion is a rare event. This case is likely the result of insufficient osseous integration. Patients undergoing cervical TDR should avoid high-risk activities to prevent trauma that could compromise the disc's placement, and future design/research should focus on how to enhance osseous integration at the interface while minimizing excessive heterotopic ossification.

Lateral Condyle Fracture of the Humerus in Children Treated with Bioabsorbable Materials

PubMed Central

Tercier, Stéphane; Bregou-Bourgeois, Aline; Zambelli, Pierre-Yves

2013-01-01

The aim of this study was to compare clinical and radiological outcome of lateral condyle fracture of the elbow in children treated with bioabsorbable or metallic material. From January 2008 to December 2009, 16 children with similar fractures and ages were grouped according to the fixation material used. Children were seen at 3, 6, and 12 months and more than 4 years (mean 51.8 months) postoperatively. The clinical results were compared using the Mayo Elbow Performance Score (MEPS). Radiographic studies of the fractured and opposite elbow were assessed at last follow-up control. Twelve children had a sufficient followup and could be included in the study. Seven could be included in the traditional group and 5 in the bioabsorbable group. At 12 months, the MEPS was 100 for every child in both groups. Asymptomatic bony radiolucent visible tracks and heterotopic ossifications were noted in both groups. There were no significant differences in terms of clinical and radiological outcome between the two groups. The use of bioabsorbable pins or screws is a reasonable alternative to the traditional use of metallic materials for the treatment of lateral condyle fracture of the elbow in children. PMID:24228016

Epileptogenic networks in nodular heterotopia: A stereoelectroencephalography study.

PubMed

Pizzo, Francesca; Roehri, Nicolas; Catenoix, Hélène; Medina, Samuel; McGonigal, Aileen; Giusiano, Bernard; Carron, Romain; Scavarda, Didier; Ostrowsky, Karine; Lepine, Anne; Boulogne, Sébastien; Scholly, Julia; Hirsch, Edouard; Rheims, Sylvain; Bénar, Christian-George; Bartolomei, Fabrice

2017-12-01

Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings. Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3). A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection. This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1 Is Necessary for Normal Endochondral Ossification and Aggrecan Metabolism*

PubMed Central

Sato, Takashi; Kudo, Takashi; Ikehara, Yuzuru; Ogawa, Hiroyasu; Hirano, Tomoko; Kiyohara, Katsue; Hagiwara, Kozue; Togayachi, Akira; Ema, Masatsugu; Takahashi, Satoru; Kimata, Koji; Watanabe, Hideto; Narimatsu, Hisashi

2011-01-01

Chondroitin sulfate (CS) is a glycosaminoglycan, consisting of repeating disaccharide units of N-acetylgalactosamine and glucuronic acid residues, and plays important roles in development and homeostasis of organs and tissues. Here, we generated and analyzed mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGalNAcT-1). Csgalnact1−/− mice were viable and fertile but exhibited slight dwarfism. Biochemically, the level of CS in Csgalnact1−/− cartilage was reduced to ∼50% that of wild-type cartilage, whereas its chain length was similar to wild-type mice, indicating that CSGalNAcT-1 participates in the CS chain initiation as suggested in the previous study (Sakai, K., Kimata, K., Sato, T., Gotoh, M., Narimatsu, H., Shinomiya, K., and Watanabe, H. (2007) J. Biol. Chem. 282, 4152–4161). Histologically, the growth plate of Csgalnact1−/− mice contained shorter and slightly disorganized chondrocyte columns with a reduced volume of the extracellular matrix principally in the proliferative layer. Immunohistochemical analysis revealed that the level of both aggrecan and link protein 1 were decreased in Csgalnact1−/− cartilage. Western blot analysis demonstrated an increase in processed forms of aggrecan core protein. These results suggest that CSGalNAcT-1 is required for normal levels of CS biosynthesis in cartilage. Our observations suggest that CSGalNAcT-1 is necessary for normal levels of endochondral ossification, and the decrease in CS amount in the growth plate by its absence causes a rapid catabolism of aggrecan. PMID:21148564

Transformation of the pectoral girdle in the evolutionary origin of frogs: insights from the primitive anuran Discoglossus

PubMed Central

Havelková, Pavla; Roček, Zbyněk

2006-01-01

Using cleared-and-stained whole mounts and computer-aided three-dimensional reconstructions made from serial histological sections, we studied the development of the pectoral girdle in Discoglossus pictus, an extant member of an ancient frog lineage, represented for example by Eodiscoglossus from the Middle Jurassic to Early Cretaceous periods in Europe. Basic developmental features were compared with those of extinct Temnospondyli, considered to be the most probable anuran ancestors, and with Triadobatrachus, an early Triassic proanuran. In the endochondral girdle, the separate scapula and coracoid of Discoglossus and other anurans (completed by suprascapular and procoracoid cartilages) evolved from the compact scapulocoracoid of temnospondyls by paedomorphosis. In parallel, the dermal ossifications of the girdle were reduced to a small clavicle and cleithrum. The overall reduction in ossification of the anuran pectoral girdle supports the hypothesis of a paedomorphic origin for Anura. The almost simultaneous appearance of dermal and endochondral ossifications may be explained by the accumulation of developmental events during a short, distinct metamorphosis (which did not occur in neotenic temnospondyls living permanently in water). The sternal elements seem to be neomorphs for the most part, which help to cushion the shock of landing in jumping anurans but which also evolved as functional substitutes (insertion area for the pectoralis muscles) of the temnospondyl interclavicle. PMID:16822264

Comparison of clinical outcomes in decompression and fusion versus decompression only in patients with ossification of the posterior longitudinal ligament: a meta-analysis.

PubMed

Mehdi, Syed K; Alentado, Vincent J; Lee, Bryan S; Mroz, Thomas E; Benzel, Edward C; Steinmetz, Michael P

2016-06-01

OBJECTIVE Ossification of the posterior longitudinal ligament (OPLL) is a pathological calcification or ossification of the PLL, predominantly occurring in the cervical spine. Although surgery is often necessary for patients with symptomatic neurological deterioration, there remains controversy with regard to the optimal surgical treatment. In this systematic review and meta-analysis, the authors identified differences in complications and outcomes after anterior or posterior decompression and fusion versus after decompression alone for the treatment of cervical myelopathy due to OPLL. METHODS A MEDLINE, SCOPUS, and Web of Science search was performed for studies reporting complications and outcomes after decompression and fusion or after decompression alone for patients with OPLL. A meta-analysis was performed to calculate effect summary mean values, 95% CIs, Q statistics, and I(2) values. Forest plots were constructed for each analysis group. RESULTS Of the 2630 retrieved articles, 32 met the inclusion criteria. There was no statistically significant difference in the incidence of excellent and good outcomes and of fair and poor outcomes between the decompression and fusion and the decompression-only cohorts. However, the decompression and fusion cohort had a statistically significantly higher recovery rate (63.2% vs 53.9%; p < 0.0001), a higher final Japanese Orthopaedic Association score (14.0 vs 13.5; p < 0.0001), and a lower incidence of OPLL progression (< 1% vs 6.3%; p < 0.0001) compared with the decompression-only cohort. There was no statistically significant difference in the incidence of complications between the 2 cohorts. CONCLUSIONS This study represents the only comprehensive review of outcomes and complications after decompression and fusion or after decompression alone for OPLL across a heterogeneous group of surgeons and patients. Based on these results, decompression and fusion is a superior surgical technique compared with posterior

Clinical staging of Fibrodysplasia Ossificans Progressiva (FOP).

PubMed

Pignolo, Robert J; Kaplan, Frederick S

2018-04-01

Fibrodyplasia ossificans progressiva (FOP) is an ultra-rare genetic condition of heterotopic ossification (HO) that results in progressive loss of joint function, ultimately rendering movement impossible. Death is most commonly the result of thoracic insufficiency syndrome, or complications related to recurrent respiratory infections. There are no current treatments for FOP, but early and emerging clinical trials offer hope for this devastating disease. With the recent reporting of a comprehensive global natural history study, scales to assess joint dysfunction, and a more accurate prediction of joint survival, it is now possible to construct a conceptual framework for the clinical staging of FOP. Based on assessment of FOP features in seven areas, it is possible to assign five clinical stages. FOP features include flare-up activity, body regions affected, thoracic insufficiency, other complications, activities of daily living (ADLs), ambulatory status, and the cumulative joint involvement scale (CAJIS) score. Assessments of these features assign an individual with FOP to early/mild, moderate, severe, profound, or late-stage disease. These criteria seek to be flexible enough to be used by clinicians without reliance on advanced imaging or specialized testing, as well as by investigators involved in research or clinical trial studies who would have these tools available. These staging measures for FOP assess the influence of HO and accelerated joint dysfunction (due to congenital abnormalities) on the ability to perform common functional activities, and thus a delay or lack of progression from one stage to the next represents the ultimate test of efficacy for drug trials. This framework will serve both as a prediction tool for FOP progression as well as a critical opportunity to substantiate therapeutic interventions. The staging system proposed here will permit an accurate assessment of severity to appropriately develop or revise clinical plans of care, define

Skeletal heterochrony is associated with the anatomical specializations of snakes among squamate reptiles.

PubMed

Werneburg, Ingmar; Sánchez-Villagra, Marcelo R

2015-01-01

Snakes possess a derived anatomy, characterized by limb reduction and reorganization of the skull and internal organs. To understand the origin of snakes from an ontogenetic point of view, we conducted comprehensive investigations on the timing of skeletal elements, based on published and new data, and reconstructed the evolution of the ossification sequence among squamates. We included for the first time Varanus, a critical taxon in phylogenetic context. There is comprehensive delay in the onset of ossification of most skeletal elements in snakes when compared to reference developmental events through evolution. We hypothesize that progressing deceleration accompanied limb reduction and reorganization of the snake skull. Molecular and morphological studies have suggested close relationship of snakes to either amphisbaenians, scincids, geckos, iguanids, or varanids. Likewise, alternative hypotheses on habitat for stem snakes have been postulated. Our comprehensive heterochrony analyses detected developmental shifts in ossification for each hypothesis of snake origin. Moreover, we show that reconstruction of ancestral developmental sequences is a valuable tool to understand ontogenetic mechanisms associated with major evolutionary changes and test homology hypotheses. The "supratemporal" of snakes could be homolog to squamosal of other squamates, which starts ossification early to become relatively large in snakes. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

2016-02-01

During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

New developmental evidence clarifies the evolution of wrist bones in the dinosaur-bird transition.

PubMed

Botelho, João Francisco; Ossa-Fuentes, Luis; Soto-Acuña, Sergio; Smith-Paredes, Daniel; Nuñez-León, Daniel; Salinas-Saavedra, Miguel; Ruiz-Flores, Macarena; Vargas, Alexander O

2014-09-01

From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowing whole-mount immunofluorescence of the embryonic cartilaginous skeleton. Beyond previous controversy, we establish that the proximal-anterior ossification develops from a composite radiale+intermedium cartilage, consistent with fusion of radiale and intermedium observed in some theropod dinosaurs. Despite previous claims that the development of the distal-anterior ossification does not support the dinosaur-bird link, we found its embryonic precursor shows two distinct regions of both collagen type II and collagen type IX expression, resembling the composite semilunate bone of bird-like dinosaurs (distal carpal 1+distal carpal 2). The distal-posterior ossification develops from a cartilage referred to as "element x," but its position corresponds to distal carpal 3. The proximal-posterior ossification is perhaps most controversial: It is labelled as the ulnare in palaeontology, but we confirm the embryonic ulnare is lost during development. Re-examination of the fossil evidence reveals the ulnare was actually absent in bird-like dinosaurs. We confirm the proximal-posterior bone is a pisiform in terms of embryonic position and its development as a sesamoid associated to a tendon. However, the pisiform is absent in bird-like dinosaurs, which are known from several articulated specimens. The combined data provide compelling evidence of a remarkable evolutionary reversal: A large, ossified pisiform re-evolved in the lineage leading to birds, after a period in which it was either absent, nonossified, or very small, consistently escaping fossil preservation. The bird wrist provides a modern example of how developmental and paleontological data illuminate

1,25-Dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification.

PubMed

Stumpf, W E; Koike, N; Hayakawa, N; Tokuda, K; Nishimiya, K; Tsuchiya, Y; Hirate, J; Okazaki, A; Kumaki, K

1994-09-01

Target cells for 3H-labeled 1 alpha, 25(OH)2 vitamin D3 [1,25(OH)2D3, vitamin D] and its analog 3H-labeled 22-oxa-1 alpha, 25(OH)2 vitamin D3 (OCT) have been identified during endochondral and intramembranous ossification in developing, undecalcified, unembedded bone, using thaw-mount autoradiography. Two-day-old neonatal rats were injected with [3H]1,25(OH)2D3 or [3H]OCT; after 2 h leg, spine, and head were frozen and sectioned. In the epiphyseal-metaphyseal region specific nuclear concentrations of [3H]1,25(OH)2D3 and [3H]OCT were observed in identical cell populations, being low in cells of the articular and resting zone, intermediate in the proliferating zone, and highest in hypertrophic chondrocytes and in osteoblasts and precursor cells. In the primary spongiosa intertrabecular spaces there were a large number of cells with nuclear labeling--probably osteoblasts and precursor cells. In contrast, in the secondary spongiosa intertrabecular spaces, apparent blood-forming cells were mostly unlabeled. Osteoblasts along bone spicules and compact bone in long bones, vertebrae, and head also showed strong nuclear labeling, as did cells of the periosteum. These data suggest that 1,25(OH)2D3 and OCT regulate development, differentiation, and activities of chondrocytes and osteoblasts, including differentiation of resting chondrocytes into proliferating and hypertrophic chondrocytes that involve "chondroclastic" enlargement of lacunae and "trans-differentiation" of surviving hypertrophic chondrocytes; differentiation of stroma cells into osteoblasts; and in periosteum and other regions of intramembranous ossification differentiation of precursor cells and osteoblasts. Nuclear receptor binding and their selective and hierarchical distribution during cell differentiation appear to correspond to multiple genomic effects toward growth, regeneration and repair. The findings indicate a physiological significance and therapeutic potential of 1,25(OH)2D3 and in particular of

Heterotopic vascularized lymph node transfer to the medial calf without a skin paddle for restoration of lymphatic function: Proof of concept.

PubMed

Smith, Mark L; Molina, Bianca J; Dayan, Erez; Saint-Victor, Diane S; Kim, Julie N; Kahn, Eugene S; Kagen, Alexander; Dayan, Joseph H

2017-01-01

The use of heterotopic vascularized lymph node transfer (HVLNT) for the treatment of lower extremity lymphedema is still evolving. Current techniques, either place the lymph nodes in the thigh without a skin paddle or at the ankle requiring an unsightly and often bulky skin paddle for closure. We explored the feasibility of doing a below-knee transfer without a skin paddle using the medial sural vessels as recipient vessels and report our experience in 21 patients. A retrospective review of all patients who underwent HVLNT to the medial calf was performed. Postoperative magnetic resonance angiography (MRA) and lymphoscintigraphy (LS) were analyzed to assess lymph node viability and function after transfer. Twenty-one patients underwent HVLNT to the medial calf. Postoperative imaging was performed at an average of 11 months after surgery. Thirteen patients had postoperative MRA, of whom 12 demonstrated viable lymph nodes. Seven patients underwent postoperative LS, of whom three demonstrated uptake in the transferred nodes. In the other four patients, the injectate failed to reach the level of the proximal calf. We provide proof of concept that HVLNT to the lower leg using the medial sural vessels without a skin paddle can result in viable and functional lymph nodes in the setting of lower extremity lymphedema. J. Surg. Oncol. 2017;115:90-95. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ossification of the posterior longitudinal ligament related genes identification using microarray gene expression profiling and bioinformatics analysis.

PubMed

He, Hailong; Mao, Lingzhou; Xu, Peng; Xi, Yanhai; Xu, Ning; Xue, Mingtao; Yu, Jiangming; Ye, Xiaojian

2014-01-10

Ossification of the posterior longitudinal ligament (OPLL) is a kind of disease with physical barriers and neurological disorders. The objective of this study was to explore the differentially expressed genes (DEGs) in OPLL patient ligament cells and identify the target sites for the prevention and treatment of OPLL in clinic. Gene expression data GSE5464 was downloaded from Gene Expression Omnibus; then DEGs were screened by limma package in R language, and changed functions and pathways of OPLL cells compared to normal cells were identified by DAVID (The Database for Annotation, Visualization and Integrated Discovery); finally, an interaction network of DEGs was constructed by string. A total of 1536 DEGs were screened, with 31 down-regulated and 1505 up-regulated genes. Response to wounding function and Toll-like receptor signaling pathway may involve in the development of OPLL. Genes, such as PDGFB, PRDX2 may involve in OPLL through response to wounding function. Toll-like receptor signaling pathway enriched genes such as TLR1, TLR5, and TLR7 may involve in spine cord injury in OPLL. PIK3R1 was the hub gene in the network of DEGs with the highest degree; INSR was one of the most closely related genes of it. OPLL related genes screened by microarray gene expression profiling and bioinformatics analysis may be helpful for elucidating the mechanism of OPLL. © 2013.

Defective Endochondral Ossification-Derived Matrix and Bone Cells Alter the Lymphopoietic Niche in Collagen X Mouse Models

PubMed Central

Sweeney, Elizabeth; Roberts, Douglas; Lin, Angela; Guldberg, Robert

2013-01-01

Despite the appreciated interdependence of skeletal and hematopoietic development, the cell and matrix components of the hematopoietic niche remain to be fully defined. Utilizing mice with disrupted function of collagen X (ColX), a major hypertrophic cartilage matrix protein associated with endochondral ossification, our data identified a cytokine defect in trabecular bone cells at the chondro-osseous hematopoietic niche as a cause for aberrant B lymphopoiesis in these mice. Specifically, analysis of ColX transgenic and null mouse chondro-osseous regions via micro-computed tomography revealed an altered trabecular bone environment. Additionally, cocultures with hematopoietic and chondro-osseous cell types highlighted impaired hematopoietic support by ColX transgenic and null mouse derived trabecular bone cells. Further, cytokine arrays with conditioned media from the trabecular osteoblast cocultures suggested an aberrant hematopoietic cytokine milieu within the chondro-osseous niche of the ColX deficient mice. Accordingly, B lymphopoiesis was rescued in the ColX mouse derived trabecular osteoblast cocultures with interlukin-7, stem cell factor, and stromal derived factor-1 supplementation. Moreover, B cell development was restored in vivo after injections of interlukin-7. These data support our hypothesis that endrochondrally-derived trabecular bone cells and matrix constituents provide cytokine-rich niches for hematopoiesis. Furthermore, this study contributes to the emerging concept that niche defects may underlie certain immuno-osseous and hematopoietic disorders. PMID:23656481

Defective endochondral ossification-derived matrix and bone cells alter the lymphopoietic niche in collagen X mouse models.

PubMed

Sweeney, Elizabeth; Roberts, Douglas; Lin, Angela; Guldberg, Robert; Jacenko, Olena

2013-10-01

Despite the appreciated interdependence of skeletal and hematopoietic development, the cell and matrix components of the hematopoietic niche remain to be fully defined. Utilizing mice with disrupted function of collagen X (ColX), a major hypertrophic cartilage matrix protein associated with endochondral ossification, our data identified a cytokine defect in trabecular bone cells at the chondro-osseous hematopoietic niche as a cause for aberrant B lymphopoiesis in these mice. Specifically, analysis of ColX transgenic and null mouse chondro-osseous regions via micro-computed tomography revealed an altered trabecular bone environment. Additionally, cocultures with hematopoietic and chondro-osseous cell types highlighted impaired hematopoietic support by ColX transgenic and null mouse derived trabecular bone cells. Further, cytokine arrays with conditioned media from the trabecular osteoblast cocultures suggested an aberrant hematopoietic cytokine milieu within the chondro-osseous niche of the ColX deficient mice. Accordingly, B lymphopoiesis was rescued in the ColX mouse derived trabecular osteoblast cocultures with interlukin-7, stem cell factor, and stromal derived factor-1 supplementation. Moreover, B cell development was restored in vivo after injections of interlukin-7. These data support our hypothesis that endrochondrally-derived trabecular bone cells and matrix constituents provide cytokine-rich niches for hematopoiesis. Furthermore, this study contributes to the emerging concept that niche defects may underlie certain immuno-osseous and hematopoietic disorders.

Choice of surgical approach for ossification of the posterior longitudinal ligament in combination with cervical disc hernia.

PubMed

Yang, Hai-song; Chen, De-yu; Lu, Xu-hua; Yang, Li-li; Yan, Wang-jun; Yuan, Wen; Chen, Yu

2010-03-01

Ossification of the posterior longitudinal ligament (OPLL) is a common spinal disorder that presents with or without cervical myelopathy. Furthermore, there is evidence suggesting that OPLL often coexists with cervical disc hernia (CDH), and that the latter is the more important compression factor. To raise the awareness of CDH in OPLL for spinal surgeons, we performed a retrospective study on 142 patients with radiologically proven OPLL who had received surgery between January 2004 and January 2008 in our hospital. Plain radiograph, three-dimensional computed tomography construction (3D CT), and magnetic resonance imaging (MRI) of the cervical spine were all performed. Twenty-six patients with obvious CDH (15 of segmental-type, nine of mixed-type, two of continuous-type) were selected via clinical and radiographic features, and intraoperative findings. By MRI, the most commonly involved level was C5/6, followed by C3/4, C4/5, and C6/7. The areas of greatest spinal cord compression were at the disc levels because of herniated cervical discs. Eight patients were decompressed via anterior cervical discectomy and fusion (ACDF), 13 patients via anterior cervical corpectomy and fusion (ACCF), and five patients via ACDF combined with posterior laminectomy and fusion. The outcomes were all favorable. In conclusion, surgeons should consider the potential for CDH when performing spinal cord decompression and deciding the surgical approach in patients presenting with OPLL.

Choice of surgical approach for ossification of the posterior longitudinal ligament in combination with cervical disc hernia

PubMed Central

Yang, Hai-song; Lu, Xu-hua; Yang, Li–li; Yan, Wang-jun; Yuan, Wen; Chen, Yu

2009-01-01

Ossification of the posterior longitudinal ligament (OPLL) is a common spinal disorder that presents with or without cervical myelopathy. Furthermore, there is evidence suggesting that OPLL often coexists with cervical disc hernia (CDH), and that the latter is the more important compression factor. To raise the awareness of CDH in OPLL for spinal surgeons, we performed a retrospective study on 142 patients with radiologically proven OPLL who had received surgery between January 2004 and January 2008 in our hospital. Plain radiograph, three-dimensional computed tomography construction (3D CT), and magnetic resonance imaging (MRI) of the cervical spine were all performed. Twenty-six patients with obvious CDH (15 of segmental-type, nine of mixed-type, two of continuous-type) were selected via clinical and radiographic features, and intraoperative findings. By MRI, the most commonly involved level was C5/6, followed by C3/4, C4/5, and C6/7. The areas of greatest spinal cord compression were at the disc levels because of herniated cervical discs. Eight patients were decompressed via anterior cervical discectomy and fusion (ACDF), 13 patients via anterior cervical corpectomy and fusion (ACCF), and five patients via ACDF combined with posterior laminectomy and fusion. The outcomes were all favorable. In conclusion, surgeons should consider the potential for CDH when performing spinal cord decompression and deciding the surgical approach in patients presenting with OPLL. PMID:20012451

Heterotopic Ossification in Combat Amputees from Afghanistan and Iraq wars: Five Case Histories and Results from a Small Series of Patients

DTIC Science & Technology

2011-01-01

symptoms. This patient also had severe soft-tissue injuries to his nonamputated left arm that required a skin graft . Subse- quent to surgery, the...illustrates the use of preventive medi- cation and symptomatic HO following breakdown of a skin graft . This patient had bilateral transfemoral amputa...United States. He was fitted with prostheses and successfully learned to walk. This patient had a split-thickness skin graft on his right residual

Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia

PubMed Central

Li, Hui-Jie; Xu, Yong; Zhang, Ke-Rang; Hoptman, Matthew J.; Zuo, Xi-Nian

2014-01-01

Background The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy – a measure of interhemispheric connection – and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. Methods Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric inter-hemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). Results EOS patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. Conclusions Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status. PMID:25130214

[Case-control study on comprehensive traditional Chinese medicine therapy for preventing postsurgery stiffness after operation for terrible triad of the elbow].

PubMed

Lin, Guang-Mao; Liu, Liang-Le; Ye, Li-Jie; Li, Qi; Liu, Mei-Fen

2014-11-01

To study therapeutic effects of comprehensive traditional Chinese medicine therapy for preventing postsurgery stiffness after operation for terrible triad of the elbow. From December 2008 to December 2013,32 patients with elbow triad were randomly divided into two groups: therapy group and control group. There were 17 patients in control group including 12 males and 5 females with a mean age of (41.0 ± 7.1) years old. The patients in control group were received the past procedure therapy. There were 15 patients in therapy group, including 10 males and 5 females with a mean age of (41.3 ± 7.6) years old. The patients in therapy group were received comprehensive traditional Chinese medicine therapy, including passive exercise training at early stage (0 to 2 weeks after operation), transition from passive to active exercise training at middle stage (3 to 4 weeks after operation), and active exercise training at late stage (5 to 12 weeks after operation). Other treatment methods, such as orally taking or externally use of Chinese herbal medicine, manipulation and physiotherapy, were used at all stages. The Mayo Elbow Performance Score, patient satisfaction and complications were evaluated and analyzed. All the patients were followed up, and the mean duration was 7.5 months. There were no complications such as internal fixation loosing, obvious displacement fracture and heterotopic ossification occurred. The Mayo score and patient satisfaction in therapy group were higher than those in control group (t = 12.78, P = 0.00; χ2 = 8.719, P = 0.003). Seven patients needed reoperation in control group, compared with 1 patient in therapy group (χ2 = 4.626, P = 0.032). The comprehensive traditional Chinese medicine therapy is effective to prevent postoperative stiffness after operation for terrible triad of the elbow by using different methods at different stages, which is worthy of spread and application.

Pseudohypoparathyroidism Type 1A-Subclinical Hypothyroidism and Rapid Weight Gain as Early Clinical Signs: A Clinical Review of 10 Cases

PubMed Central

Kayemba-Kay’s, Simon; Tripon, Cedric; Heron, Anne; Hindmarsh, Peter

2016-01-01

Objective: To evaluate the clinical signs and symptoms that would help clinicians to consider pseudohypoparathyroidism (PHP) type 1A as a diagnosis in a child. Methods: A retrospective review of the medical records of children diagnosed by erythrocyte Gsα activity and/or GNAS1 gene study and followed-up for PHP type 1A. Clinical and biochemical parameters along with epidemiological data were extracted and analyzed. Weight gain during infancy and early childhood was calculated as change in weight standard deviation score (SDS), using the French growth reference values. An upward gain in weight ≥0.67 SDS during these periods was considered indicative of overweight and/or obesity. Results: Ten cases of PHP type 1A were identified (mean age 41.1 months, range from 4 to 156 months). In children aged ≤2 years, the commonest clinical features were round lunar face, obesity (70%), and subcutaneous ossifications (60%). In older children, brachydactyly was present in 60% of cases. Seizures occurred in older children (3 cases). Short stature was common at all ages. Subclinical hypothyroidism was present in 70%, increased parathormone (PTH) in 83%, and hyperphosphatemia in 50%. Only one case presented with hypocalcemia. Erythrocyte Gsα activity tested in seven children was reduced; GNAS1 gene testing was performed in 9 children. Maternal transmission was the most common (six patients). In three other cases, the mutations were de novo, c.585delGACT in exon 8 (case 2) and c.344C>TP115L in exon 5 (cases 6&7). Conclusion: Based on our results, PHP type 1A should be considered in toddlers presenting with round face, rapid weight gain, subcutaneous ossifications, and subclinical hypothyroidism. In older children, moderate mental retardation, brachydactyly, afebrile seizures, short stature, and thyroid-stimulating hormone resistance are the most suggestive features. PMID:27467896

Multiple intracranial calcifications and spinal compressions: rare complications of type la pseudohypoparathyroidism.

PubMed

Chen, H; Tseng, F; Su, D; Chen, H; Tsai, K

2005-01-01

Type la pseudohypoparathyroidism (PHP la) is an unusual inherited disease. PHP la often causes extraskeletal calcifications and even soft tissue ossifications. Patients may present neurologic symptoms and signs related to hypocalcemia and hyperphosphatemia. We report here a 38-yr-old woman with PHP la who had two uncommon neurologic complications. One was involuntary movements related to basal ganglia calcification, and the other was myelopathy owing to ossifications of the posterior longitudinal ligament and multiple herniated intervertebral disks. Aggressive body weight control and corrections of hypocalcemia, hyperphosphatemia, and elevated PTH may be important to prevent these unusual neurologic complications. Regular and careful neurologic examinations should be performed for early diagnosis and treatments of these spinal lesions.

Nontraumatic Myositis Ossificans of Hip: A Case Presentation

PubMed Central

Ozcan, Muhammed Sefa

2016-01-01

In most of the cases trauma is the leading etiology and the nontraumatic myositis ossificans (MO) is a very rare condition. We present an MO case without any trauma occurring. A 36-year-old female patient with a history of pain and restriction of range of motion of the left hip was admitted. Hip motions were restricted with 10–60° of flexion, 10° of internal rotation, 20° of external rotation, 10° of abduction, and 10° of adduction. There was no history of trauma and familial involvement. The biopsy of the lesion revealed mature bone tissue confirming our diagnosis of MO. The mass was removed surgically and postoperatively the patient was treated with a single dose radiotherapy with 800 gyc. MO is a benign and well differentiated bone formation or in other words heterotopic ossification of the muscle tissue. It has a prevalence of less than 1/1 million. Trauma is the most frequent etiological factor seen in almost 60–75% of the cases. Nontraumatic MO is very rare in the literature. Our patient had no history of trauma or familial involvement. Combination of the surgical excision with radiotherapy in the treatment of the MO of the hip may give satisfactory results. PMID:27437157

Case report: severe melorheostosis involving the ipsilateral extremities.

PubMed

Long, Hai-Tao; Li, Kang-Hua; Zhu, Yong

2009-10-01

Melorheostosis is a rare, noninheritable bone dysplasia characterized by its classic radiographic feature of flowing hyperostosis resembling dripping candle wax, generally on one side of the long bone. The condition originally was described by Leri and Joanny in 1922. Its etiology remains speculative, and treatment in most instances has been symptomatic. Melorheostosis usually affects one limb, more often the lower extremity, and rarely the axial skeleton. We report a rare case of severe melorheostosis in the ipsilateral upper and lower extremities with normal contralateral extremities. The plain radiographs revealed almost all the bones in the affected extremities, from clavicle and scapula to distal phalanges of the fingers and from femur to distal phalanges of the toes, presented extensive, dense hyperostosis and heterotopic ossification in the periarticular soft tissue. Physical examination showed considerable swelling and deformities of the left limbs, stiffness and distortion of the joints, and anesthesia in the left ulnar regions of the forearm and hand. The examination of the right side was normal. Computed tomography scans showed multiple areas of classic candle wax-like hyperostosis and narrowing or disappearance of the medullary cavity. Histologic analysis confirmed the clinical and imaging diagnosis and revealed extremely dense sclerotic bone of cortical pattern.

Cervical artificial disc extrusion after a paragliding accident

PubMed Central

Niu, Tianyi; Hoffman, Haydn; Lu, Daniel C.

2017-01-01

Background: Cervical total disc replacement (TDR) is an established alternative to anterior cervical discectomy and fusion (ACDF) with excellent long-term outcomes and low failure rates. Cases of implant failure and migration are scarce and primarily limited to several years postoperatively. The authors report a case of anterior extrusion of a C4-C5 ProDisc-C (DePuy Synthes, West Chester, PA, USA) cervical artificial disc (CAD) 14 months after placement due to minor trauma. Case Description: A 33-year-old female who had undergone C4-C5 CAD implantation presented with neck pain and spasm after experiencing a paragliding accident. A 4 mm anterior protrusion of the CAD was seen on x-ray. She underwent removal of the CAD followed by anterior fusion. Other cases of CAD extrusion in the literature are discussed and the device's durability and testing are considered. Conclusion: Overall, CAD extrusion is a rare event. This case is likely the result of insufficient osseous integration. Patients undergoing cervical TDR should avoid high-risk activities to prevent trauma that could compromise the disc's placement, and future design/research should focus on how to enhance osseous integration at the interface while minimizing excessive heterotopic ossification. PMID:28781915

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

PubMed

Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

Effectiveness of autologous fibrin tissue adhesive in reducing postoperative blood loss during total hip arthroplasty: a prospective randomised study of 100 cases.

PubMed

Mawatari, M; Higo, T; Tsutsumi, Y; Shigematsu, M; Hotokebuchi, T

2006-08-01

To evaluate the effectiveness of autologous fibrin tissue adhesive (auto-FTA) in reducing blood loss during cementless total hip arthroplasty (THA). From September 2000 to August 2001, 100 patients who predonated 400 ml of autologous blood were randomised to undergo either standard treatment with auto-FTA (auto-FTA group) or standard treatment alone (control group). The volume of postoperative blood loss and the decrease in haemoglobin level were measured. All patients were followed up for 3 years to evaluate the rate of bone ingrowth and heterotopic ossification. The mean postoperative blood loss was 580 ml (standard deviation [SD], 240 ml) in the auto-FTA group and 810 ml (SD, 341 ml) in the control group; the difference was significant (230 ml, p<0.001). The decrease in haemoglobin concentration was 17 g/l (SD, 11 g/l) in the auto-FTA group and 22 g/l (SD, 12 g/l) in the control group. The difference was significant (5 g/l, p=0.03). The percentage of total blood loss of >1200 ml in any single patient was significantly lower in the auto-FTA group (4%) than in the control group (20%) [p=0.01]. Auto-FTA is a safe and effective means of reducing perioperative blood loss in THA.

Bird embryos uncover homology and evolution of the dinosaur ankle.

PubMed

Ossa-Fuentes, Luis; Mpodozis, Jorge; Vargas, Alexander O

2015-11-13

The anklebone (astragalus) of dinosaurs presents a characteristic upward projection, the 'ascending process' (ASC). The ASC is present in modern birds, but develops a separate ossification centre, and projects from the calcaneum in most species. These differences have been argued to make it non-comparable to dinosaurs. We studied ASC development in six different orders of birds using traditional techniques and spin-disc microscopy for whole-mount immunofluorescence. Unexpectedly, we found the ASC derives from the embryonic intermedium, an ancient element of the tetrapod ankle. In some birds it comes in contact with the astragalus, and, in others, with the calcaneum. The fact that the intermedium fails to fuse early with the tibiale and develops an ossification centre is unlike any other amniotes, yet resembles basal, amphibian-grade tetrapods. The ASC originated in early dinosaurs along changes to upright posture and locomotion, revealing an intriguing combination of functional innovation and reversion in its evolution.

Bird embryos uncover homology and evolution of the dinosaur ankle

PubMed Central

Ossa-Fuentes, Luis; Mpodozis, Jorge; Vargas, Alexander O

2015-01-01

The anklebone (astragalus) of dinosaurs presents a characteristic upward projection, the ‘ascending process' (ASC). The ASC is present in modern birds, but develops a separate ossification centre, and projects from the calcaneum in most species. These differences have been argued to make it non-comparable to dinosaurs. We studied ASC development in six different orders of birds using traditional techniques and spin–disc microscopy for whole-mount immunofluorescence. Unexpectedly, we found the ASC derives from the embryonic intermedium, an ancient element of the tetrapod ankle. In some birds it comes in contact with the astragalus, and, in others, with the calcaneum. The fact that the intermedium fails to fuse early with the tibiale and develops an ossification centre is unlike any other amniotes, yet resembles basal, amphibian-grade tetrapods. The ASC originated in early dinosaurs along changes to upright posture and locomotion, revealing an intriguing combination of functional innovation and reversion in its evolution. PMID:26563435

Heterotopic bone formation around sintered porous-surfaced Ti-6Al-4V implants coated with native bone morphogenetic proteins.

PubMed

Simon, Ziv; Deporter, Douglas A; Pilliar, Robert M; Clokie, Cameron M

2006-09-01

Coating endosseous dental implants with growth factors such as bone morphogenetic proteins (BMPs) may be one way to accelerate and/or enhance the quality of osseointegration. The purpose of this study was to investigate in the murine muscle pouch model whether sintered porous-surfaced titanium alloy implants coated with BMPs would lead to heterotopic bone formation around and within the implant surface geometry. Porous-surfaced dental implants were coated with partially purified native human BMPs, with or without a carrier of Poloxamer 407 (BASF Corp., Parsippany, NJ), placed in gelatin capsules and implanted into the hindquarter muscles of mice. Mice were euthanized after 28 days. Sections of retrieved specimens were subsequently prepared for morphometric analysis of bone formation using backscatter electron microscopic images. Human BMPs, either with or without the carrier of Poloxamer 407, led to bone formation within and outside of the sintered porous implant surface. When the sintered implant surface region was subdivided into inner and outer halves, similar levels of bone ingrowth and contact were seen in the 2 halves. Evidence of bone formation to the depth of the solid implant core (i.e., the deepest level possible) also was seen. Sintered porous-surfaced dental implants can be used as substrate for partially purified BMPs in the murine muscle pouch model. With the addition of these osteoinductive factors, the porous implant surface supported bone formation within the surface porosity provided, in some instances, all the way to the solid implant core. The addition of growth factors to a sintered porous surface may be an efficient method for altering locally the healing sequence and quality of bone associated with osseointegration of bone-interfacing implants.

Zero-profile integrated plate and spacer device reduces rate of adjacent-level ossification development and dysphagia compared to ACDF with plating and cage system.

PubMed

Yang, Haisong; Chen, Deyu; Wang, Xinwei; Yang, Lili; He, Hailong; Yuan, Wen

2015-06-01

Retrospective case-control study. To compare the safety and efficacy of the Zero-profile (Zero-p) integrated plate and spacer device to that of an anterior cervical plate and cage in patients undergoing anterior cervical discectomy and fusion (ACDF). Anterior cervical plating system has provided good results, including higher fusion rate and improved alignment since its use. However, adjacent-level ossification development (ALOD) and dysphagia have been usually reported associating with plates. This was a retrospective control study. Sixty-two patients with cervical radiculopathy or myelopathy were treated with an anterior plate and cage or Zero-p implant between January 2011 and December 2011. The mean follow-up was 33.1 months in the plate and cage group and 30.6 months in Zero-p group. Patient demographics, operative details and complications were reviewed. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scores and JOA recovery rate before and after operations. Incidence of cephalad and caudal ALOD on the lateral radiographs was studied at preoperation, immediate postoperation and last follow-up. Incidence of dysphagia was also recorded after operation according to Bazaz-Yoo dysphagia index. Thirty-two patients received an anterior plate and cage and 30 received the Zero-p implant. There were no statistical differences in patient demographics, operative details between the two groups. The JOA scores significantly increased compared with preoperational measurements in both groups (p < 0.05), but the JOA recovery rate was similar (72.2 % for plate and cage group and 77.0 % for Zero-p group, p > 0.05). ALOD occurred in 12 (18.8 %) of the 64 cephalad and caudal adjacent segments in plate with cage group, and only 1 (1.6 %) of 63 adjacent levels (including three noncontiguous cases) presented with ALOD in Zero-p group. The difference was significant (p < 0.01). The incidence of dysphagia in the Zero-p group was lower

New Developmental Evidence Clarifies the Evolution of Wrist Bones in the Dinosaur–Bird Transition

PubMed Central

Botelho, João Francisco; Ossa-Fuentes, Luis; Soto-Acuña, Sergio; Smith-Paredes, Daniel; Nuñez-León, Daniel; Salinas-Saavedra, Miguel; Ruiz-Flores, Macarena; Vargas, Alexander O.

2014-01-01

From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowing whole-mount immunofluorescence of the embryonic cartilaginous skeleton. Beyond previous controversy, we establish that the proximal–anterior ossification develops from a composite radiale+intermedium cartilage, consistent with fusion of radiale and intermedium observed in some theropod dinosaurs. Despite previous claims that the development of the distal–anterior ossification does not support the dinosaur–bird link, we found its embryonic precursor shows two distinct regions of both collagen type II and collagen type IX expression, resembling the composite semilunate bone of bird-like dinosaurs (distal carpal 1+distal carpal 2). The distal–posterior ossification develops from a cartilage referred to as “element x,” but its position corresponds to distal carpal 3. The proximal–posterior ossification is perhaps most controversial: It is labelled as the ulnare in palaeontology, but we confirm the embryonic ulnare is lost during development. Re-examination of the fossil evidence reveals the ulnare was actually absent in bird-like dinosaurs. We confirm the proximal–posterior bone is a pisiform in terms of embryonic position and its development as a sesamoid associated to a tendon. However, the pisiform is absent in bird-like dinosaurs, which are known from several articulated specimens. The combined data provide compelling evidence of a remarkable evolutionary reversal: A large, ossified pisiform re-evolved in the lineage leading to birds, after a period in which it was either absent, nonossified, or very small, consistently escaping fossil preservation. The bird wrist provides a modern example of how developmental and paleontological

An Endochondral Ossification-Based Approach to Bone Repair: Chondrogenically Primed Mesenchymal Stem Cell-Laden Scaffolds Support Greater Repair of Critical-Sized Cranial Defects Than Osteogenically Stimulated Constructs In Vivo.

PubMed

Thompson, Emmet M; Matsiko, Amos; Kelly, Daniel J; Gleeson, John P; O'Brien, Fergal J

2016-03-01

The lack of success associated with the use of bone grafts has motivated the development of tissue engineering approaches for bone defect repair. However, the traditional tissue engineering approach of direct osteogenesis, mimicking the process of intramembranous ossification (IMO), leads to poor vascularization. In this study, we speculate that mimicking an endochondral ossification (ECO) approach may offer a solution by harnessing the potential of hypertrophic chondrocytes to secrete angiogenic signals that support vasculogenesis and enhance bone repair. We hypothesized that stimulation of mesenchymal stem cell (MSC) chondrogenesis and subsequent hypertrophy within collagen-based scaffolds would lead to improved vascularization and bone formation when implanted within a critical-sized bone defect in vivo. To produce ECO-based constructs, two distinct scaffolds, collagen-hyaluronic acid (CHyA) and collagen-hydroxyapatite (CHA), with proven potential for cartilage and bone repair, respectively, were cultured with MSCs initially in the presence of chondrogenic factors and subsequently supplemented with hypertrophic factors. To produce IMO-based constructs, CHA scaffolds were cultured with MSCs in the presence of osteogenic factors. These constructs were subsequently implanted into 7 mm calvarial defects on Fischer male rats for up to 8 weeks in vivo. The results demonstrated that IMO- and ECO-based constructs were capable of supporting enhanced bone repair compared to empty defects. However, it was clear that the scaffolds, which were previously shown to support the greatest cartilage formation in vitro (CHyA), led to the highest new bone formation (p < 0.05) within critical-sized bone defects 8 weeks postimplantation. We speculate this to be associated with the secretion of angiogenic signals as demonstrated by the higher VEGF protein production in the ECO-based constructs before implantation leading to the greater blood vessel ingrowth. This study thus

Cranial Morphology of the Brachystelechid ‘Microsaur’ Quasicaecilia texana Carroll Provides New Insights into the Diversity and Evolution of Braincase Morphology in Recumbirostran ‘Microsaurs’

PubMed Central

Pardo, Jason D.; Szostakiwskyj, Matt; Anderson, Jason S.

2015-01-01

Recumbirostran ‘microsaurs,’ a group of early tetrapods from the Late Carboniferous and Early Permian, are the earliest known example of adaptation to head-first burrowing in the tetrapod fossil record. However, understanding of the diversity of fossorial adaptation within the Recumbirostra has been hindered by poor anatomical knowledge of the more divergent forms within the group. Here we report the results of μCT study of Quasicaecilia texana, a poorly-known recumbirostran with a unique, broad, shovel-like snout. The organization of the skull roof and braincase of Quasicaecilia is found to be more in line with that of other recumbirostrans than previously described, despite differences in overall shape. The braincase is found to be broadly comparable to Carrolla craddocki, with a large presphenoid that encompasses much of the interorbital septum and the columella ethmoidalis, and a single compound ossification encompassing the sphenoid, otic, and occipital regions. The recumbirostran braincase conserves general structure and topology of braincase regions and cranial nerve foramina, but it is highly variable in the number of ossifications and their extent, likely associated with the reliance on braincase ossifications to resist compression during sediment compaction and mechanical manipulation by epaxial and hypaxial musculature. Expansion of the deep ventral neck musculature in Quasicaecilia, autapomorphic among recumbirostrans, may reflect unique biomechanical function, and underscores the importance of future attention to the role of the cervical musculature in contextualizing the origin and evolution of fossoriality in recumbirostrans. PMID:26107260

Arthroplasty for cervical spondylotic myelopathy: similar results to patients with only radiculopathy at 3 years' follow-up.

PubMed

Fay, Li-Yu; Huang, Wen-Cheng; Wu, Jau-Ching; Chang, Hsuan-Kan; Tsai, Tzu-Yun; Ko, Chin-Chu; Tu, Tsung-Hsi; Wu, Ching-Lan; Cheng, Henrich

2014-09-01

Cervical arthroplasty has been accepted as a viable option for surgical management of cervical spondylosis or degenerative disc disease (DDD). The best candidates for cervical arthroplasty are young patients who have radiculopathy caused by herniated disc with competent facet joints. However, it remains uncertain whether arthroplasty is equally effective for patients who have cervical myelopathy caused by DDD. The aim of this study was to compare the outcomes of arthroplasty for patients with cervical spondylotic myelopathy (CSM) and patients with radiculopathy without CSM. A total of 151 consecutive cases involving patients with CSM or radiculopathy caused by DDD and who underwent one- or two-level cervical arthroplasty were included in this study. Clinical outcome evaluations and radiographic studies were reviewed. Clinical outcome measurements included the Visual Analog Scale (VAS) of neck and arm pain, Japanese Orthopaedic Association (JOA) scores, and the Neck Disability Index (NDI) in every patient. For patients with CSM, Nurick scores were recorded for evaluation of cervical myelopathy. Radiographic studies included lateral dynamic radiographs and CT for detection of the formation of heterotopic ossification . Of the 151 consecutive patients with cervical DDD, 125 (82.8%; 72 patients in the myelopathy group and 53 in the radiculopathy group) had at least 24 months of clinical and radiographic follow-up. The mean duration of follow-up in these patients was 36.4 months (range 24-56 months). There was no difference in sex distribution between the 2 groups. However, the mean age of the patients in the myelopathy group was approximately 6 years greater than that of the radiculopathy group (53.1 vs 47.2 years, p < 0.001). The mean operation time, mean estimated blood loss, and the percentage of patients prescribed perioperative analgesic agents were similar in both groups (p = 0.754, 0.652, and 0.113, respectively). There were significant improvements in VAS neck

Controversies in Treatment of Acetabular Fracture

PubMed Central

Grubor, Predrag; Krupic, Ferid; Biscevic, Mirza; Grubor, Milan

2015-01-01

ossification, periarticular hetero-tropic calcifications after surgical treatment were: 0° in 65 patients (79%), I-II° in 9 patients (11%) and III-IV ° in 8 patients (10%). Calcifications in 14 patients treated with traction of heterotopic ossification by Brook-s classification were as follows: 0° in 10 patients (72%), I-II ° in 3 patients (22%) and III-IV° in 1 patient (6%). Conclusion: At the occurrence of acetabular fracture, it is necessary to start the treatment immediately, with an obligatory application of thromboembolic and antibiotic prophylaxis. Conservative treatment is acceptable if the dislocation of fracture is less than 5 mm. Indications for surgical treatment are incongruent or unstable fractures with verified dislocation greater than 5 mm, as well as when the radiography measured by JM Matta shows incongruence of acetabular roof less than 40° in all planes. Kocher-Langenbeck approach is the choice of surgical approach for the management of posterior column / wall, and Letournel’s (ilioinguinal) approach is the choice for the management of anterior wall/column. PMID:25870470

Development of a new auxiliary heterotopic partial liver transplantation technique using a liver cirrhosis model in minipigs: Preliminary report of eight transplants

PubMed Central

ZHANG, JUN-JING; NIU, JIAN-XIANG; YUE, GEN-QUAN; ZHONG, HAI-YAN; MENG, XING-KAI

2012-01-01

This study aimed to develop a new auxiliary heterotopic partial liver transplantation (AHPLT) technique in minipigs using a model of liver cirrhosis. Based on our previous study, 14 minipigs were induced to cirrhosis by administration of carbon tetrachloride (CCl4) through intraperitoneal injection. All of the cirrhotic animals were utilized as recipients. The donor’s liver was placed on the recipient’s splenic bed, and the anastomosis was performed as follows: end-to-end anastomosis between the donor’s portal vein and the recipient’s splenic vein, end-to-side anastomosis between the donor’s suprahepatic vena cava and the recipient’s suprahepatic vena cava, and end-to-end anastomosis between the donor’s hepatic artery and the recipient’s splenic artery. The common bile duct of the donor was intubated and bile was collected with an extracorporeal bag. Vital signs, portal vein pressure (PVP), hepatic venous pressure (HVP) and portal vein pressure gradient (PVPG) were monitored throughout the transplantation. All 8 minipigs that developed liver cirrhosis were utilized to establish the new AHPLT; 7 cases survived. Following the surgical intervention, the PVP and PVPG of the recipients were lower than those prior to the operation (P<0.05), whereas the PVP and PVPG of the donors increased significantly compared to those of the normal animals (P<0.05). A new operative technique for AHPLT has been successfully described herein using a model of liver cirrhosis. PMID:22969983

Clinical course of patients with ossification of the posterior longitudinal ligament: a minimum 10-year cohort study.

PubMed

Matsunaga, Shunji; Sakou, Takashi; Taketomi, Eiji; Komiya, Setsuro

2004-03-01

Ossification of the posterior longitudinal ligament (OPLL) may produce quadriplegia. The course of future neurological deterioration in patients with radiographic evidence of OPLL, however, is not known. The authors conducted a long-term follow-up cohort study of more than 10 years to clarify the clinical course of this disease progression. A total of 450 patients, including 304 managed conservatively and 146 treated by surgery, were enrolled in the study. All patients underwent neurological and radiographical follow-up examinations for a mean of 17.6 years. Myelopathy was graded using Nurick classification and the Japanese Orthopaedic Association scale. Fifty-five (17%) of 323 patients without myelopathy evident at the first examination developed myelopathy during the follow-up period. Risk factors associated with the evolution of myelopathy included greater than 60% OPLL-induced stenotic compromise of the cervical canal, and increased range of motion of the cervical spine. Using Kaplan-Meier analysis, the myelopathy-free rate in patients without first-visit myelopathy was 71% after 30 years. A significant difference in final functional outcome was not observed between nonsurgical and surgical cases in which preoperative Nurick grades were 1 or 2. In patients with Nurick Grade 3 or 4 myelopathy, however, only 12% who underwent surgery eventually became wheelchair bound or bedridden compared with 89% of those managed conservatively. Surgery proved ineffective in the management of patients with Grade 5 disease. Results of this long-term cohort study elucidated the clinical course of OPLL following conservative or surgical management. Surgery proved effective for the management of patients with Nurick Grades 3 and 4 myelopathy.

Endochondral Ossification Is Accelerated in Cholinesterase-Deficient Mice and in Avian Mesenchymal Micromass Cultures

PubMed Central

Spieker, Janine; Mudersbach, Thomas; Vogel-Höpker, Astrid; Layer, Paul G.

2017-01-01

Most components of the cholinergic system are detected in skeletogenic cell types in vitro, yet the function of this system in skeletogenesis remains unclear. Here, we analyzed endochondral ossification in mutant murine fetuses, in which genes of the rate-limiting cholinergic enzymes acetyl- (AChE), or butyrylcholinesterase (BChE), or both were deleted (called here A-B+, A+B-, A-B-, respectively). In all mutant embryos bone growth and cartilage remodeling into mineralizing bone were accelerated, as revealed by Alcian blue (A-blu) and Alizarin red (A-red) staining. In A+B- and A-B- onset of mineralization was observed before E13.5, about 2 days earlier than in wild type and A-B+ mice. In all mutants between E18.5 to birth A-blu staining disappeared from epiphyses prematurely. Instead, A-blu+ cells were dislocated into diaphyses, most pronounced so in A-B- mutants, indicating additive effects of both missing ChEs in A-B- mutant mice. The remodeling effects were supported by in situ hybridization (ISH) experiments performed on cryosections from A-B- mice, in which Ihh, Runx2, MMP-13, ALP, Col-II and Col-X were considerably decreased, or had disappeared between E18.5 and P0. With a second approach, we applied an improved in vitro micromass model from chicken limb buds that allowed histological distinction between areas of cartilage, apoptosis and mineralization. When treated with the AChE inhibitor BW284c51, or with nicotine, there was decrease in cartilage and accelerated mineralization, suggesting that these effects were mediated through nicotinic receptors (α7-nAChR). We conclude that due to absence of either one or both cholinesterases in KO mice, or inhibition of AChE in chicken micromass cultures, there is increase in cholinergic signalling, which leads to increased chondroblast production and premature mineralization, at the expense of incomplete chondrogenic differentiation. This emphasizes the importance of cholinergic signalling in cartilage and bone

Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation.

PubMed

Piché, Mathieu; Watanabe, Nobuhiro; Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Ishiwata, Kiichi; Hotta, Harumi

2014-01-01

The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (p<0.05), a late component of SEP that reflects activity in the anterior cingulate cortex. This reduction was associated with higher basal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Multipurpose contrast enhancement on epiphyseal plates and ossification centers for bone age assessment

PubMed Central

2013-01-01

Background The high variations of background luminance, low contrast and excessively enhanced contrast of hand bone radiograph often impede the bone age assessment rating system in evaluating the degree of epiphyseal plates and ossification centers development. The Global Histogram equalization (GHE) has been the most frequently adopted image contrast enhancement technique but the performance is not satisfying. A brightness and detail preserving histogram equalization method with good contrast enhancement effect has been a goal of much recent research in histogram equalization. Nevertheless, producing a well-balanced histogram equalized radiograph in terms of its brightness preservation, detail preservation and contrast enhancement is deemed to be a daunting task. Method In this paper, we propose a novel framework of histogram equalization with the aim of taking several desirable properties into account, namely the Multipurpose Beta Optimized Bi-Histogram Equalization (MBOBHE). This method performs the histogram optimization separately in both sub-histograms after the segmentation of histogram using an optimized separating point determined based on the regularization function constituted by three components. The result is then assessed by the qualitative and quantitative analysis to evaluate the essential aspects of histogram equalized image using a total of 160 hand radiographs that are implemented in testing and analyses which are acquired from hand bone online database. Result From the qualitative analysis, we found that basic bi-histogram equalizations are not capable of displaying the small features in image due to incorrect selection of separating point by focusing on only certain metric without considering the contrast enhancement and detail preservation. From the quantitative analysis, we found that MBOBHE correlates well with human visual perception, and this improvement shortens the evaluation time taken by inspector in assessing the bone age. Conclusions

The characteristic clinical symptoms of C-4 radiculopathy caused by ossification of the posterior longitudinal ligament.

PubMed

Katsumi, Keiichi; Yamazaki, Akiyoshi; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Endo, Naoto

2014-05-01

Cervical radiculopathy of the C2-4 spinal nerves is a rare condition and is poorly documented in terms of clinical symptoms, hindering its detection during initial patient screening based on imaging diagnostics. The authors describe in detail the clinical symptoms and successful surgical treatment of a patient diagnosed with isolated C-4 radiculopathy. This 41-year-old man suffered from sleep disturbance because of pain behind the right ear, along the right clavicle, and at the back of his neck on the right side. The Jackson and Spurling tests were positive, with pain radiating to the area behind the patient's ear. Unlike in cases of radiculopathy involving the C5-8 spinal nerves, no loss of upper-extremity motor function was seen. Magnetic resonance imaging showed foraminal stenosis at the C3-4 level on the right side, and multiplanar reconstruction CT revealed a beak-type ossification of the posterior longitudinal ligament in the foraminal region at the same level. In the absence of intracranial lesions or spinal cord compressive lesions, the positive Jackson and Spurling tests and the C3-4 foraminal stenosis were indicative of isolated C-4 radiculopathy. Microscopic foraminotomy was performed at the C3-4 vertebral level and the ossified lesion was resected. The patient's symptoms completely resolved immediately after surgery. To the authors' knowledge, this report is the first to describe the symptomatic features of isolated C-4 radiculopathy, in a case in which the diagnosis has been confirmed by both radiological findings and surgical outcome. Based on this case study, the authors conclude that the characteristic symptoms of C-4 radiculopathy are the presence of pain behind the ear and in the clavicular region in the absence of upper-limb involvement.

A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure.

PubMed

Lu, Wei; Zheng, Jun; Pan, Xu-Dong; Li, Bing; Zhang, Jin-Wei; Wang, Long-Fei; Sun, Li-Zhong

2015-04-01

The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique. Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively. No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients' mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3. We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation in which a working model is required.

Androgen-dependent and independent process of bone formation in the distal segment of Os penis in the rat.

PubMed

Murakami, R; Izumi, K; Yamaoka, I

1995-11-01

The distal segment of the os penis of the rat develops as a fibrocartilage which is replaced with non-lamellar bone by endochondral ossification after puberty. Development of the fibrocartilage and its calcification have been shown to be induced by androgens, but androgen-dependency of the endochondral ossification has not been studied in detail. In the present study, immature male rats of various ages were castrated and the ossification of the fibrocartilage of os penis was examined. In rats castrated at 6 weeks, when the fibrocartilage was scarcely calcified, ossification did not occur even at 24 weeks. When the castrated rats were treated with testosterone, ossification started before 12 weeks of age. In rats castrated at 8 weeks, when the fibrocartilage was heavily calcified, endochondral ossification was observed in some of the animals (5/7) at 24 weeks of age. The results of this study indicate that once the fibrocartilage is calcified, the endochondral ossification can take place without androgen, although the androgen can promote the process of ossification.

Extremity War Injuries VIII: sequelae of combat injuries.

PubMed

Andersen, Romney C; D'Alleyrand, Jean-Claude G; Swiontkowski, Marc F; Ficke, James R

2014-01-01

The 2013 Extremity War Injury symposium focused on the sequelae of combat-related injuries, including posttraumatic osteoarthritis, amputations, and infections. Much remains to be learned about posttraumatic arthritis, and there are few circumstances in which a definitive arthroplasty should be performed in an acutely injured and open joint. Although the last decade has seen tremendous advances in the treatment of combat upper extremity injuries, many questions remain unanswered, and continued research focusing on improving reconstruction of large segmental defects remains critical. Discussion of infection centered on the need for novel methods to reduce the bacterial load following the initial débridement procedures. Novel methods of delivering antimicrobial therapy and anti-inflammatory medications directly to the wound were discussed as well as the need for near real-time assessment of bacterial and fungal burden and further means of prevention and treatment of biofilm formation and the importance of animal models to test therapies discussed. Moderators and lecturers of focus groups noted the continuing need for improved prehospital care in the management of junctional injuries, identified optimal strategies for both surgical repair and/or reconstruction of the ligaments in multiligamentous injuries, and noted the need to mitigate bone mineral density loss following amputation and/or limb salvage as well as the necessity of developing better methods of anticipating and managing heterotopic ossification.

Longitudinal patient-reported mobility assessment in fibrodysplasia ossificans progressiva (FOP).

PubMed

Kaplan, Frederick S; Al Mukaddam, Mona; Pignolo, Robert J

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling genetic disorder characterized by episodic soft tissue swelling (flare-ups) that leads to progressive heterotopic ossification and restricted joint mobility. Here we present the first longitudinal patient-reported mobility assessment (PRMA) in FOP based on a simple evaluation tool. At initial presentation and follow-up (1-11year span; median: 6 year span), 64 patients (36 females; 28 males) with classic FOP completed a questionnaire designed to rapidly assess mobility at 15 sites (three axial; six upper limb, and six lower limb). In order to validate this instrument, twenty-one of 64 patients (33%) underwent a cumulative analogue joint involvement scale (CAJIS) evaluation by two physicians within six months of their second self-assessment. We found that: 1) mobility changes were episodic and regional, occurring first in the neck and trunk, followed by the upper limbs and finally the lower limbs; 2) interval improvements in mobility did occur, most notably in the lower limbs (18%), and less so in the upper limbs (12%) and trunk (3%), and 3) patient-reported mobility assessments correlate highly (R 2 =0.81) with physician-reported CAJIS evaluations. This is the first longitudinal PRMA in FOP and provides a simple and valid tool that can be used in the design and evaluation of clinical trials in this progressively disabling disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovery, clinical development, and therapeutic uses of bisphosphonates.

PubMed

Licata, Angelo A

2005-04-01

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R(1) and R(2)). The R(1) side chain determines binding affinity to hydroxyapatite, and the R(2) side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

Pre-surgical CT-assessment of neurogenic myositis ossificans of the hip and risk factors of recurrence: a series of 101 consecutive patients.

PubMed

Law-Ye, Bruno; Hangard, Chloé; Felter, Adrien; Safa, Dominique; Denormandie, Philippe; Genet, François; Carlier, Robert-Yves

2016-10-18

Neurogenic Myositis Ossificans (NMO) is a rare disabling pathology characterized by peri-articular heterotopic ossifications following severe peripheral or central nervous system injuries. It results in ankylosis and vessels or nerves compressions. Our study aimed to describe the pre-operative findings of patients with NMO of the hip using biphasic computerized tomography (CT). Between 2006 and 2012, we retrospectively analyzed 101 consecutive patients with hip NMO. We analyzed all CTs and surgical reports following a standardized grid depicting the osteoma and its relations with joint capsule, vessels and nerves and bone mineralization. We studied surgical complications and recurrence during follow-up. Chi2-test and Fischer's test were performed to compare qualitative values with respectively normal and non-normal distribution. Quantitative values were analyzed with a one factor analysis of variance (ANOVA) test. Agreement between pre-surgical CT and surgical observations was evaluated with Cohen's kappa test. Correlation between pre-operative CT and surgical findings was excellent regarding relationships with vessels (0,82) and was good concerning relationships with sciatic nerves (0.62) and with joint capsule (0.68). Close contact or disruption of joint capsule (p = 0.005), joint space narrowing (p = 0.007) and bone demineralization (p < 0.001) were correlated with NMO recurrence. Biphasic enhanced-CT allows pre-operative assessment of NMO with good correlation to surgical observations and helps prevent surgical complications.

Prospective long-term follow-up of the cementless bicontact hip stem with plasmapore coating.

PubMed

Ochs, U; Eingartner, C; Volkmann, R; Ochs, B G; Huber, C; Weller, S; Weise, K

2007-01-01

A prospective long-term study of the first 250 cementless Bicontact stems implanted in the BG Trauma Centre, Tuebingen, Germany. All of the patients in this series (treatment period June 1987 to April 1990) who were still contactable were invited for clinical and radiological follow-up. The radiographs were analysed for signs of loosening in the form of Gruen lysis zones, stress shielding, subsidence behaviour, heterotopic ossification and spot welds. The average follow-up period was 17.8 (16.7 - 19.5) years. The overall rate of follow-up was 65 % (162 of 250) and 91 % of patients who were still alive (162 of 179). The average patient age was 56.2 years at the time of operation and 74.0 years at follow-up. The average HHS was 81.6 points. In the course of the first 10 years (up to 03/1998), a total of 8 stem revisions had to be performed. In the period from 03/1998 to 01/2007, 2 cases of loosening requiring revision occurred in the patients still alive at the time of follow-up. The survival rate calculated was thus 95.6 %. These outstanding results provide enduring support for the philosophy of the cementless and bone-preserving fixation principles underlying the Bicontact hip stem with proximal intertrochanteric transmission of forces and high primary rotational stability.

Distal biceps tendon rupture reconstruction using muscle-splitting double-incision approach

PubMed Central

Tarallo, Luigi; Mugnai, Raffaele; Zambianchi, Francesco; Adani, Roberto; Catani, Fabio

2014-01-01

AIM: To evaluate the clinical and functional results after repair of distal biceps tendon tears, following the Morrey’s modified double-incision approach. METHODS: We retrospectively reviewed 47 patients with distal rupture of biceps brachii treated between 2003 and 2012 in our Orthopedic Department with muscle-splitting double-incision technique. Outcome measures included the Mayo elbow performance, the DASH questionnaire, patient’s satisfaction, elbow and forearm motion, grip strength and complications occurrence. RESULTS: At an average 18 mo follow-up (range, 7 mo-10 years) the average Mayo elbow performance and DASH score were respectively 97.2 and 4.8. The elbow flexion range was 94%, extension was -2°, supination was 93% and pronation 96% compared with the uninjured limb. The mean grip strength, expressed as percentage of respective contralateral limb, was 83%. The average patient satisfaction rating on a Likert scale (from 0 to 10) was 9.4. The following complications were observed: 3 cases of heterotopic ossification (6.4%), one (2.1%) re-rupture of the tendon at the site of reattachment and 2 cases (4.3%) of posterior interosseous nerve palsy. No complication required further surgical treatment. CONCLUSION: This technique allows an anatomic reattachment of distal biceps tendon at the radial tuberosity providing full functional recovery with low complication rate. PMID:25133147

The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model.

PubMed

Ibrahim, Nurul 'Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

2015-10-16

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II-VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.

Diagnosis and endoscopic treatment of esophago-bronchial fistula due to gastric heterotopy.

PubMed

Katsanos, Konstantinos H; Christodoulou, Dimitrios K; Kamina, Sevasti; Maria, Kosmidou; Lambri, Evangelia; Theodorou, Stavroula; Tsampoulas, Konstantinos; Vasiliki, Mitsi; Tsianos, Epameinondas V

2010-04-16

Heterotopic gastric mucosa patches are congenital gastrointestinal abnormalities and have been reported to occur anywhere along the gastrointestinal tract from mouth to anus. Complications of heterotopic gastric mucosa include dysphagia, upper gastrointestinal bleeding, upper esophageal ring stricture, adenocarcinoma and fistula formation. In this case report we describe the diagnosis and treatment of the first case of esophago-bronchial fistula due to heterotopic gastric mucosa in mid esophagus. A 40-year old former professional soccer player was referred to our department for treatment of an esophago-bronchial fistula. Microscopic examination of the biopsies taken from the esophageal fistula revealed the presence of gastric heterotopic mucosa. We decided to do a non-surgical therapeutic endoscopic procedure. A sclerotherapy catheter was inserted through which 1 mL of ready to use synthetic surgical glue was applied in the fistula and it closed the fistula opening with excellent results.

[Replantation at lower leg level].

PubMed

Daigeler, A; Fansa, H; Westphal, T; Schneider, W

2003-11-01

Replantation in reconstructive surgery is an established procedure due to microsurgical techniques. It can be routinely performed in unilateral lower leg amputation. In some cases of bilateral amputation, in which orthotopic replantation is not possible due to the complex trauma, heterotopic replantation is a therapeutic option. This avoids prosthetic fitting. We report five cases of orthotopic and two of heterotopic lower limb replantations. Functional outcome concerning sensibility, mobility, pain, and aesthetic result were assessed clinically and using a questionnaire. Functional outcome and patient satisfaction were good. The psychological situation of the patients as well as mobility and stability of the replanted limbs were satisfying. Heterotopically replanted patients found the replanted legs superior to the prostheses. We conclude that, in lower leg amputation, attempts should be made to replant the extremity. In bilateral lower leg amputations, at least one limb should be reconstructed, even if "only" a heterotopic replantation can be performed.

Combined use of leptin and mechanical stress has osteogenic effects on ossification of the posterior longitudinal ligament.

PubMed

Chen, Shuai; Zhu, Haifeng; Wang, Gangliang; Xie, Ziang; Wang, Jiying; Chen, Jian

2018-06-16

To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy. Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting. Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress. Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

A new rat model of auxiliary partial heterotopic liver transplantation with liver dual arterial blood supply.

PubMed

Qiao, Jianliang; Han, Chunlei; Zhang, Junjing; Wang, Zhiyong; Meng, Xingkai

2015-02-01

Auxiliary partial heterotopic liver transplantation (APHLT) with portal vein arterialization is a valuable procedure to be considered in the treatment of patients with acute liver failure and metabolic liver diseases. The aim of this study was to develop a new rat model of APHLT with liver dual arterial blood supply (LDABS). A total of 20 rats were used. The donor liver was resected, and the celiac trunk was reserved. Left and medial hepatic lobes accounting for 70% of the liver mass were removed en bloc and the suprahepatic caval vein was ligated simultaneously. Thus, 30% of the donor liver was obtained as the graft. Sleeve anastomosis of the graft portal vein and splenic artery were performed after narrowing the portal vein lumen through suturing. The right kidney of the recipient was removed, and sleeve anastomosis was performed between the celiac trunk of the graft and the right renal artery of the recipient. In addition, end-to-end anastomosis was performed between the infrahepatic caval vein of the graft and the right renal vein of the recipient. Following the reperfusion of the graft, the blood flow of the arterialized portal vein was controlled within the physiological range through suturing and narrowing under monitoring with an ultrasonic flowmeter. The bile duct of the graft was implanted into the duodenum of the recipient through an internal stent catheter. A 70% section of the native liver (left and medial hepatic lobes) was resected using bloodless hepatectomy. The mean operative duration was 154.5±16.4 min, and the warm and cold ischemia times of the graft were 8.1±1.1 min and 64.5±6.6 min, respectively. The blood flow of the arterialized portal vein to the graft was 1.8±0.3 ml/min/g liver weight. The success rate of model establishment (waking with post-surgical survival of >24 h) was 70% (7/10). Following successful model establishment, all rats survived 7 days post-surgery (100%; 7/7). The graft was found to be soft in texture and bright red

Microendoscopic posterior decompression for the treatment of thoracic myelopathy caused by ossification of the ligamentum flavum: a technical report.

PubMed

Baba, Satoshi; Oshima, Yasushi; Iwahori, Tomoyuki; Takano, Yuichi; Inanami, Hirohiko; Koga, Hisashi

2016-06-01

Ossification of the ligamentum flavum (OLF) is a common cause of progressive thoracic myelopathy in East Asia. Good surgical results are expected for patients who already show myelopathy. Surgical decompression using a posterior approach is commonly used to treat OLF. This study investigated the use of microendoscopic posterior decompression for the treatment of thoracic OLF. Microendoscopic posterior decompression was performed on 9 patients with myelopathy. Patients had a mean age of 59.8 years and single-level involvement, mostly at the T10-11 and T11-12 vertebrae. Computed tomography and magnetic resonance imaging were used to classify the OLF. A tubular retractor and endoscopic system were used for microendoscopic posterior decompression. Midline and unilateral paramedian approaches were performed in 2 and 7 patients, respectively. Intraoperative motor evoked potentials (MEPs) of 7 patients were monitored. Pre- and postoperative neurological status was evaluated using the modified Japanese Orthopaedic Association (mJOA) score. Thoracic OLF for all patients were classed as bilateral type with a round morphology. Improvement of MEPs at least one muscle area was recorded in all patients following posterior decompression. A dural tear in one patient was the only observed complication. The mean recovery rate was 44.9 %, as calculated from mJOA scores at a mean follow-up period of 20 months. Microendoscopic posterior decompression combined with MEP monitoring can be used to treat patients with thoracic OLF. The optimal surgical indication is OLF at a single vertebral level and of a unilateral or bilateral nature, without comma and tram track signs, and a round morphology.

[Multiple stones in atypical heterotopic reservoir in a patient with renal transplant: endourologic resolution].

PubMed

Pietro, Granelli; Antonio, Frattini; Stefania, Ferretti; Paolo, Salsi; Davide, Campobasso; Matteo, Moretti; Enzo, Capocasale; Patrizia, Mazzoni; Pietro, Cortellini; Granelli, Pietro; Frattini, Antonio; Ferretti, Stefania; Salsi, Paolo; Campobasso, Davide; Moretti, Matteo; Capocasale, Enzo; Mazzoni, Patrizia; Cortellini, Pietro

2011-10-01

Urolithiasis is a frequent complication in a heterotopic reservoir and the surgical management could be a difficult problem. Open surgery is not recommended in patients with multiple previous surgeries. A less invasive technique, such as the endourologic procedures, would allow high stone-free rate and low surgical morbidity. Stone formation in the reservoir is a well-known complication of urinary diversion. The incidence of lithiasis in patients with continent urinary diversion is reported as 12-52.5%. Most patients will have multiple physical factors, such as immobility, need for self-catheterization and poor urine drainage, so that it is not certain that an intestinal reservoir is the cause of stones on its own. The management of urolithiasis in continent urinary diversion can be challenging and could be a difficult problem to solve. A less invasive technique, such as the endourologic procedures, is desiderable, especially in patients with kidney transplant and low immune defence. We present the case of a 59-year-old woman with previous history of spina bifida and with neurogenic bladder. At a pediatric age, she underwent incontinent urinary diversion using a sigmo-colic conduit. For several years she had been suffering from kidney stones and recurrent urinary infections, which led to a left nephrectomy for pyonephrosis, subsequent deterioration of renal function and dialysis. In 2004, we performed an atypical continent and self-catheterizable reservoir using the previous colic conduit detubularized and ileum-cecal tract with Mitrofanoff system conduit of 14 Fr size. Finally, kidney transplant was carried out as last surgical procedure. Recently she has come to our attention for multiple and large reservoir stones. preliminary exploration of the continent pouch with flexible cystoscope. Percutaneous access with Endovision° direct control through the afferent conduit with 8 Fr flexible ureteroscope. Dilation of percutaneous tract with pneumatic balloon and

Formation of the Periotic Space During the Early Fetal Period in Humans.

PubMed

Ishikawa, Aoi; Ohtsuki, Sae; Yamada, Shigehito; Uwabe, Chigako; Imai, Hirohiko; Matsuda, Tetsuya; Takakuwa, Tetsuya

2018-04-01

The inner ear is a very complicated structure, composed of a bony labyrinth (otic capsule; OC), membranous labyrinth, with a space between them, named the periotic labyrinth or periotic space. We investigated how periotic tissue fluid spaces covered the membranous labyrinth three-dimensionally, leading to formation of the periotic labyrinth encapsulated in the OC during human fetal development. Digital data sets from magnetic resonance images and phase-contrast X-ray tomography images of 24 inner ear organs from 24 human fetuses from the Kyoto Collection (fetuses in trimesters 1 and 2; crown-rump length: 14.4-197 mm) were analyzed. The membranous labyrinth was morphologically differentiated in samples at the end of the embryonic period (Carnegie stage 23), and had grown linearly to more than eight times in size during the observation period. The periotic space was first detected at the 35-mm samples, around the vestibule and basal turn of the cochlea, which elongated rapidly to the tip of the cochlea and semicircular ducts, successively, and almost covered the membranous labyrinth at the 115-mm CRL stage or later. In those samples, several ossification centers were detected around the space. This article thus demonstrated that formation of the membranous labyrinth, periotic space (labyrinth), and ossification of the OC occurs successively, according to an intricate timetable. Anat Rec, 301:563-570, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Glial heterotopia in an adult: A rare orbital mass.

PubMed

Sundaresh, Divya Dabir; Mangala Gouri, S R

2016-11-01

Heterotopic glial tissue is very rare in the orbit. Our case was an adult, which is unique since most cases reported in literature involve children. We describe a case of a 60-year-old man who presented with an orbital mass, which histopathologically revealed heterotopic glial tissue.

Unusual Case of Combined Gliomeningeal Heterotopia on the Nose of an Infant.

PubMed

Schauer, Anna; Harvey, Nathan T; Vijayasekaran, Shyan; Wood, Benjamin A

2017-10-24

Nasal glial heterotopia ("nasal glioma") and cutaneous heterotopic meningeal nodules ("primary cutaneous meningioma") are rare congenital lesions characterized by the presence of heterotopic mature cerebral tissues. Nasal glial heterotopia occurs predominantly in the nasal area and typically does not contain meningothelial elements, whereas heterotopic meningeal nodules occur predominantly on the scalp and do not contain glial elements. In this article, we report an unusual case of cutaneous heterotopia on the nose of an infant composed of both glial and meningothelial elements. The glial component was characterized by irregular islands of predominantly astrocytic cells, on a fibrillary background. The meningothelial component was characterized by bland ovoid cells with focal intranuclear inclusions forming whorled arrangements, with associated psammomatous calcification. To our knowledge, this is the first time such a lesion has been documented. It has also provided us with an opportunity to review the literature regarding heterotopic deposits of both glial and meningothelial tissues.

Hip arthroscopy for femoroacetabular impingement: the changing nature and severity of associated complications over time.

PubMed

Park, Myung-Sik; Yoon, Sun-Jung; Kim, Yong-Jin; Chung, Woo-Chul

2014-08-01

The aim of this study was to assess complications related to arthroscopy for femoroacetabular impingement (FAI) and how these complications have changed as we have gained more experience with this procedure. The authors reviewed 200 hips (197 patients). The average patient age was 44.64 years and the mean follow-up time was 28.2 months. All patients underwent hip arthroscopy in the supine position. Clinically, Modified Harris Hip Scores (MHHS) and patient satisfaction with outcome were used. We divided complications into 3 groups: Group 1 related to traction, group 2 related to surgical technique or implant failure, and group 3 related to outcomes. Clinically, the MHHS improved from 69.96 (±6.10) to 80.45 (±7.00), and patient satisfaction with the achieved outcome increased to 8.87 (±0.76). The overall complication rate was 15% (30 of 200 hips). Group 1 consisted of 4 patients with pudendal neuropraxia and 2 patients with ankle joint pain (P = .013). Group 2 consisted of 2 patients with lateral femoral cutaneous neuropraxia, 2 patients with iatrogenic labral perforations, one patient with a labral tear, and 4 patients with femoral head scuffs. There were 4 incidents of instrument breakage. Furthermore, 3 suture anchors failed, a second-degree burn occurred in one patient, and there was incomplete reshaping in 5 hips (P = .045). Group 3 included one patient with a snapping sound and heterotopic ossification. Second-look arthroscopy was performed for 5 hips. All the complications outlined in groups 1 and 2 are related to the learning curve and have statistical significance (P < .05). Complications relating to hip arthroscopy took different forms during the early learning period, but overall complication rates decreased along the learning curve. Surgical technique-related complications such as problems with suture anchors and the reshaping of cam impingements were also considered during the later stage. Level IV, therapeutic case series. Copyright © 2014

Bone loss of vertebral bodies at the operative segment after cervical arthroplasty: a potential complication?

PubMed

Heo, Dong Hwa; Lee, Dong Chan; Oh, Jong Yang; Park, Choon Keun

2017-02-01

OBJECTIVE Bony overgrowth and spontaneous fusion are complications of cervical arthroplasty. In contrast, bone loss or bone remodeling of vertebral bodies at the operation segment after cervical arthroplasty has also been observed. The purpose of this study is to investigate a potential complication-bone loss of the anterior portion of the vertebral bodies at the surgically treated segment after cervical total disc replacement (TDR)-and discuss the clinical significance. METHODS All enrolled patients underwent follow-up for more than 24 months after cervical arthroplasty using the Baguera C disc. Clinical evaluations included recording demographic data and measuring the visual analog scale and Neck Disability Index scores. Radiographic evaluations included measurements of the functional spinal unit's range of motion and changes such as bone loss and bone remodeling. The grading of the bone loss of the operative segment was classified as follows: Grade 1, disappearance of the anterior osteophyte or small minor bone loss; Grade 2, bone loss of the anterior portion of the vertebral bodies at the operation segment without exposure of the artificial disc; or Grade 3, significant bone loss with exposure of the anterior portion of the artificial disc. RESULTS Forty-eight patients were enrolled in this study. Among them, bone loss developed in 29 patients (Grade 1 in 15 patients, Grade 2 in 6 patients, and Grade 3 in 8 patients). Grade 3 bone loss was significantly associated with postoperative neck pain (p < 0.05). Bone loss was related to the motion preservation effect of the operative segment after cervical arthroplasty in contrast to heterotopic ossification. CONCLUSIONS Bone loss may be a potential complication of cervical TDR and affect early postoperative neck pain. However, it did not affect mid- to long-term clinical outcomes or prosthetic failure at the last follow-up. Also, this phenomenon may result in the motion preservation effect in the operative segment

Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis.

PubMed

Hughes, Alexandria; Oxford, Alexandra E; Tawara, Ken; Jorcyk, Cheryl L; Oxford, Julia Thom

2017-03-20

Chondrocytes of the growth plate undergo apoptosis during the process of endochondral ossification, as well as during the progression of osteoarthritis. Although the regulation of this process is not completely understood, alterations in the precisely orchestrated programmed cell death during development can have catastrophic results, as exemplified by several chondrodystrophies which are frequently accompanied by early onset osteoarthritis. Understanding the mechanisms that underlie chondrocyte apoptosis during endochondral ossification in the growth plate has the potential to impact the development of therapeutic applications for chondrodystrophies and associated early onset osteoarthritis. In recent years, several chondrodysplasias and collagenopathies have been recognized as protein-folding diseases that lead to endoplasmic reticulum stress, endoplasmic reticulum associated degradation, and the unfolded protein response. Under conditions of prolonged endoplasmic reticulum stress in which the protein folding load outweighs the folding capacity of the endoplasmic reticulum, cellular dysfunction and death often occur. However, unfolded protein response (UPR) signaling is also required for the normal maturation of chondrocytes and osteoblasts. Understanding how UPR signaling may contribute to cartilage pathophysiology is an essential step toward therapeutic modulation of skeletal disorders that lead to osteoarthritis.

Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma.

PubMed

Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2016-01-01

Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT.

The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model

PubMed Central

Ibrahim, Nurul ‘Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

2015-01-01

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing. PMID:26501302

Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells.

PubMed

Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

2009-08-01

Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA.

A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

PubMed

Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

New insights in the homotopic and heterotopic connectivity of the frontal portion of the human corpus callosum revealed by microdissection and diffusion tractography.

PubMed

De Benedictis, Alessandro; Petit, Laurent; Descoteaux, Maxime; Marras, Carlo Efisio; Barbareschi, Mattia; Corsini, Francesco; Dallabona, Monica; Chioffi, Franco; Sarubbo, Silvio

2016-12-01

Extensive studies revealed that the human corpus callosum (CC) plays a crucial role in providing large-scale bi-hemispheric integration of sensory, motor and cognitive processing, especially within the frontal lobe. However, the literature lacks of conclusive data regarding the structural macroscopic connectivity of the frontal CC. In this study, a novel microdissection approach was adopted, to expose the frontal fibers of CC from the dorsum to the lateral cortex in eight hemispheres and in one entire brain. Post-mortem results were then combined with data from advanced constrained spherical deconvolution in 130 healthy subjects. We demonstrated as the frontal CC provides dense inter-hemispheric connections. In particular, we found three types of fronto-callosal fibers, having a dorso-ventral organization. First, the dorso-medial CC fibers subserve homotopic connections between the homologous medial cortices of the superior frontal gyrus. Second, the ventro-lateral CC fibers subserve homotopic connections between lateral frontal cortices, including both the middle frontal gyrus and the inferior frontal gyrus, as well as heterotopic connections between the medial and lateral frontal cortices. Third, the ventro-striatal CC fibers connect the medial and lateral frontal cortices with the contralateral putamen and caudate nucleus. We also highlighted an intricate crossing of CC fibers with the main association pathways terminating in the lateral regions of the frontal lobes. This combined approach of ex vivo microdissection and in vivo diffusion tractography allowed demonstrating a previously unappreciated three-dimensional architecture of the anterior frontal CC, thus clarifying the functional role of the CC in mediating the inter-hemispheric connectivity. Hum Brain Mapp 37:4718-4735, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genetic differences in osteogenic differentiation potency in the thoracic ossification of the ligamentum flavum under cyclic mechanical stress.

PubMed

Ning, Shanglong; Chen, Zhongqiang; Fan, Dongwei; Sun, Chuiguo; Zhang, Chi; Zeng, Yan; Li, Weishi; Hou, Xiaofei; Qu, Xiaochen; Ma, Yunlong; Yu, Huilei

2017-01-01

Mechanical stress and genetic factors play important roles in the occurrence of thoracic ossification of ligament flavum (TOLF), which can occur at one, two, or multiple levels of the spine. It is unclear whether single- and multiple-level TOLF differ in terms of osteogenic differentiation potency and osteogenesis-related gene expression under cyclic mechanical stress. This was addressed in the present study using patients with non‑TOLF and single‑ and multiple‑level TOLF (n=8 per group). Primary ligament cells were cultured and osteogenesis was induced by application of cyclic mechanical stress. Osteogenic differentiation was assessed by evaluating alkaline phosphatase (ALP) activity and the mRNA and protein expression of osteogenesis‑related genes, including ALP, bone morphogenetic protein 2 (BMP2), Runt‑related transcription factor‑2 (Runx‑2), osterix, osteopontin (OPN) and osteocalcin. The application of cyclic mechanical stress resulted in higher ALP activity in the multiple‑level than in the single‑level TOLF group, whereas no changes were observed in the non‑TOLF group. The ALP, BMP2, OPN and osterix mRNA levels were higher in the multiple‑level as compared to the single‑level TOLF group, and the levels of all osteogenesis-related genes, apart from Runx2, were higher in the multiple‑level as compared to the non‑TOLF group. The osterix and ALP protein levels were higher in the multiple‑level TOLF group than in the other 2 groups, and were increased with the longer duration of stress. These results highlight the differences in osteogenic differentiation potency between single‑ and multiple‑level TOLF that may be related to the different pathogenesis and genetic background.

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

PubMed Central

Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

2015-01-01

Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified

Skeletal development and abnormalities of the vertebral column and of the fins in hatchery-reared turbot Scophthalmus maximus.

PubMed

Tong, X H; Liu, Q H; Xu, S H; Ma, D Y; Xiao, Z Z; Xiao, Y S; Li, J

2012-03-01

To describe the skeletal development and abnormalities in turbot Scophthalmus maximus, samples were collected every day from hatching to 60 days after hatching (DAH). A whole-mount cartilage and bone-staining technique was used. Vertebral ontogeny started with the formation of anterior haemal arches at 5·1 mm standard length (L(S) ) c. 11 DAH, and was completed by the full attainment of parapophyses at 16·9 mm L(S) c. 31 DAH. Vertebral centra started to develop at 6·3 mm L(S) c. 16 DAH and ossification in all centra was visible at 11·0 mm L(S) c. 25 DAH. The caudal fin appeared at 5·1 mm L(S) c. 11 DAH and ossification was visible at 20·6 mm L(S) c. 37 DAH. The onset of dorsal and anal fin elements appeared at 5·8 mm L(S) c. 15 DAH and 6·3 mm L(S) c. 16 DAH, respectively. Ossifications of both dorsal fin and anal fin were visible at 20·6 mm L(S) c. 37 DAH. The pectorals were the only fins present before first feeding, their ossifications were completed at 23·5 mm L(S) c. 48 DAH. Pelvic fins began forming at 7·2 mm L(S) c. 19 DAH and calcification of the whole structure was visible at 19·8 mm L(S) c. 36 DAH. In the present study, 24 types of skeletal abnormalities were observed. About 51% of individuals presented skeletal abnormalities, and the highest occurrence was found in the haemal region of the vertebral column. As for each developmental stage, the most common abnormalities were in the dorsal fin during early metamorphic period (stage 2), vertebral fusion during climax metamorphosis (stage 3) and caudal fin abnormality during both late-metamorphic period (stage 4) and post-metamorphic period (stage 5). Such research will be useful for early detection of skeletal malformations during different growth periods of reared S. maximus. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Hybrid Corpectomy and Disc Arthroplasty for Cervical Spondylotic Myelopathy Caused by Ossification of Posterior Longitudinal Ligament and Disc Herniation.

PubMed

Chang, Huang-Chou; Tu, Tsung-Hsi; Chang, Hsuan-Kan; Wu, Jau-Ching; Fay, Li-Yu; Chang, Peng-Yuan; Wu, Ching-Lan; Huang, Wen-Cheng; Cheng, Henrich

2016-11-01

The combination of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) has been demonstrated to be effective for multilevel cervical spondylotic myelopathy (CSM); however, the combination of ACCF and cervical disc arthroplasty (CDA) for 3-level CSM has never been addressed. Consecutive patients (>18 years of age) with CSM caused by segmental ossification of posterior longitudinal ligament (OPLL) and degenerative disc disease (DDD) were reviewed. Inclusion criteria were patients who underwent hybrid ACCF and CDA surgery for symptomatic 3-level CSM with OPLL and DDD. Medical and radiologic records were reviewed retrospectively. A total of 15 patients were analyzed with a mean follow-up of 18.1 ± 7.42 months. Every patient had hybrid surgery composed of 1-level ACCF (for segmental-type OPLL causing spinal stenosis) and 1-level CDA at the adjacent level (for DDD causing stenosis). All clinical outcomes, including visual analogue scale of neck and arm pain, Neck Disability Index, Japanese Orthopedic Association scores, and Nurick scores of myelopathy, demonstrated significant improvement at 12 months after surgery. All patients (100%) achieved arthrodesis for the ACCF (instrumented) and preserved mobility for CDA (preoperation 6.2 ± 3.81° vs. postoperation 7.0 ± 4.18°; P = 0.579). For patients with multilevel CSM caused by segmental OPLL and DDD, the hybrid surgery of ACCF and CDA demonstrated satisfactory clinical and radiologic outcomes. Moreover, although located next to each other, the instrumented ACCF construct and CDA still achieved solid arthrodesis and preserved mobility, respectively. Therefore, hybrid surgery may be a reasonable option for the management of CSM with OPLL. Copyright © 2016 Elsevier Inc. All rights reserved.

Nano-delivery of trace minerals for marine fish larvae: influence on skeletal ossification, and the expression of genes involved in intestinal transport of minerals, osteoblast differentiation, and oxidative stress response.

PubMed

Terova, Genciana; Rimoldi, Simona; Izquierdo, Marisol; Pirrone, Cristina; Ghrab, Wafa; Bernardini, Giovanni

2018-06-17

Currently, the larviculture of many marine fish species with small-sized larvae depends for a short time after hatching, on the supply of high-quality live zooplankton to ensure high survival and growth rates. During the last few decades, the research community has made great efforts to develop artificial diets, which can completely substitute live prey. However, studies aimed at determining optimal levels of minerals in marine larvae compound feeds and the potential of novel delivery vectors for mineral acquisition has only very recently begun. Recently, the agro-food industry has developed several nano-delivery systems, which could be used for animal feed, too. Delivery through nano-encapsulation of minerals and feed additives would protect the bioactive molecules during feed manufacturing and fish feeding and allow an efficient acquisition of active substances into biological system. The idea is that dietary minerals in the form of nanoparticles may enter cells more easily than their larger counterparts enter and thus speed up their assimilation in fish. Accordingly, we evaluated the efficacy of early weaning diets fortified with organic, inorganic, or nanoparticle forms of trace minerals (Se, Zn, and Mn) in gilthead seabream (Sparus aurata) larvae. We tested four experimental diets: a trace mineral-deficient control diet, and three diets supplemented with different forms of trace minerals. At the end of the feeding trial, larvae growth performance and ossification, and the level of expression of six target genes (SLC11A2β, dmt1, BMP2, OC, SOD, GPX), were evaluated. Our data demonstrated that weaning diets supplemented with Mn, Se, and Zn in amino acid-chelated (organic) or nanoparticle form were more effective than diets supplemented with inorganic form of minerals to promote bone mineralization, and prevent skeletal anomalies in seabream larvae. Furthermore, nanometals markedly improved larval stress resistance in comparison to inorganic minerals and

The management of pediatric subtrochanteric femur fractures with a statically locked intramedullary nail.

PubMed

Herrera-Soto, José A; Meuret, Robert; Phillips, Jonathan H; Vogel, Daniel J

2015-01-01

To evaluate locked intramedullary (IM) fixation as an alternative treatment method for children with subtrochanteric fractures. Retrospective review. Level 1 trauma center in a Children's Hospital. Pediatric patients with subtrochanteric femur fractures with open growth plates. All patients were treated with a lateral entry IM locking nail. Patients were followed until full fracture consolidation or until implant removal. Data on time to full weight bearing, return to full activity, residual pain, any form of gait abnormality, and any other complication from follow-up visits were collected. There were 9 males and 1 female patient with an average age of 12 years and average follow-up of 22 months. Most of the fractures occurred secondary to high-energy trauma. Partial weight bearing was started at 24 days and full at 66 days. Implants were removed on average at 11 months after implantation. There were neither intraoperative complications nor major complications in the postoperative period recorded after removal. Two patients presented with a longer limb on the affected side, both 8 mm, and 2 presented with asymptomatic grade I heterotopic ossification. The use of a statically locked lateral entry IM nail for subtrochanteric femur fractures in children is a safe and efficacious method of treatment with few complications and risks and satisfactory outcomes in children over the age of 8 years. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Joint-specific risk of impaired function in fibrodysplasia ossificans progressiva (FOP).

PubMed

Pignolo, Robert J; Durbin-Johnson, Blythe P; Rocke, David M; Kaplan, Frederick S

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) causes progressive disability due to heterotopic ossification from episodic flare-ups. Using data from 500 FOP patients (representing 63% of all known patients world-wide), age- and joint-specific risks of new joint involvement were estimated using parametric and nonparametric statistical methods. Compared to data from a 1994 survey of 44 individuals with FOP, our current estimates of age- and joint-specific risks of new joint involvement are more accurate (narrower confidence limits), based on a wider range of ages, and have less bias due to its greater comprehensiveness (captures over three-fifths of the known FOP patients worldwide). For the neck, chest, abdomen, and upper back, the estimated hazard decreases over time. For the jaw, lower back, shoulder, elbow, wrist, fingers, hip, knee, ankle, and foot, the estimated hazard increases initially then either plateaus or decreases. At any given time and for any anatomic site, the data indicate which joints are at risk. This study of approximately 63% of the world's known population of FOP patients provides a refined estimate of risk for new involvement at any joint at any age, as well as the proportion of patients with uninvolved joints at any age. Importantly, these joint-specific survival curves can be used to facilitate clinical trial design and to determine if potential treatments can modify the predicted trajectory of progressive joint dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Select practices in management and rehabilitation of burns: a survey report.

PubMed

Holavanahalli, Radha K; Helm, Phala A; Parry, Ingrid S; Dolezal, Cynthia A; Greenhalgh, David G

2011-01-01

The purpose of this study is to document the organization and current practices in physical rehabilitation across burn centers. An online survey developed for the specific purposes of this study sought information regarding a) logistics of the burn center; b) inpatient and outpatient treatment of patients with burn injury; and c) specific protocols in the treatment of a few complications secondary to burn injuries. Of the 159 responses received, 115 were received from the United States, 20 from Australia, 16 from Canada, and 7 from New Zealand. The overall sample included responses from 76 physical therapists (PTs) and 78 occupational therapists. Seventy-three of those surveyed considered themselves primarily a burn therapist. Nurses (86%) were reported as primarily responsible for wound care of inpatients, followed by wound care technicians (24%). Ninety-seven percent of the therapists reported following their own treatment plans. The trunk and areas of head and neck were treated by both PTs and occupational therapists, whereas the lower extremities continue to be treated predominantly by PTs. Some common practices regarding treatment of a few complications secondary to burn injuries such as splinting to prevent contractures, treatment of exposed or ruptured extensor tendons, exposed Achilles tendons, heterotopic ossification, postoperative ambulation, conditioning, scar massage, and use of compression garments are described. Opportunities exist for 1) developing a common document for practice guidelines in physical rehabilitation of burns; and 2) conducting collaborative studies to evaluate treatment interventions and outcomes.

The voluntary driven exoskeleton Hybrid Assistive Limb (HAL) for postoperative training of thoracic ossification of the posterior longitudinal ligament: a case report.

PubMed

Fujii, Kengo; Abe, Tetsuya; Kubota, Shigeki; Marushima, Aiki; Kawamoto, Hiroaki; Ueno, Tomoyuki; Matsushita, Akira; Nakai, Kei; Saotome, Kosaku; Kadone, Hideki; Endo, Ayumu; Haginoya, Ayumu; Hada, Yasushi; Matsumura, Akira; Sankai, Yoshiyuki; Yamazaki, Masashi

2017-05-01

The hybrid assistive limb (HAL) is a wearable robot suit that assists in voluntary control of knee and hip joint motion by detecting bioelectric signals on the surface of the skin with high sensitivity. HAL has been reported to be effective for functional recovery in motor impairments. However, few reports have revealed the utility of HAL for patients who have undergone surgery for thoracic ossification of the posterior longitudinal ligament (thoracic OPLL). Herein, we present a postoperative thoracic OPLL patient who showed remarkable functional recovery after training with HAL. A 63-year-old woman, who could not walk due to muscle weakness before surgery, underwent posterior decompression and fusion. Paralysis was re-aggravated after the initial postoperative rising. We diagnosed that paralysis was due to residual compression from the anterior lesion and microinstability after posterior fixation, and prescribed bed rest for a further 3 weeks. The incomplete paralysis gradually recovered, and walking training with HAL was started on postoperative day 44 in addition to standard physical therapy. The patient underwent 10 sessions of HAL training until discharge on postoperative day 73. Results of a 10-m walk test were assessed after every session, and the patient's speed and cadence markedly improved. At discharge, the patient could walk with 2 crutches and no assistance. Furthermore, no adverse events associated with HAL training occurred. HAL training for postoperative thoracic OPLL patients may enhance improvement in walking ability, even if severe impairment of ambulation and muscle weakness exist preoperatively.

Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma

PubMed Central

Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2016-01-01

Summary Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

Addition of instrumented fusion after posterior decompression surgery suppresses thickening of ossification of the posterior longitudinal ligament of the cervical spine.

PubMed

Ota, Mitsutoshi; Furuya, Takeo; Maki, Satoshi; Inada, Taigo; Kamiya, Koshiro; Ijima, Yasushi; Saito, Junya; Takahashi, Kazuhisa; Yamazaki, Masashi; Aramomi, Masaaki; Mannoji, Chikato; Koda, Masao

2016-12-01

Laminoplasty (LMP) is a widely accepted surgical procedure for ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Progression of OPLL can occur in the long term after LMP. The aim of the present study was to determine whether addition of the instrumented fusion, (posterior decompression with instrumented fusion [PDF]), can suppress progression of OPLL or not. The present study included 50 patients who underwent LMP (n=23) or PDF (n=27) for OPLL of the cervical spine. We performed open door laminoplasty. PDF surgery was performed by double-door laminoplasty followed by instrumented fusion. We observed the non-ossified segment of the OPLL and measured the thickness of the OPLL at the thickest segment with pre- and postoperative sagittal CT multi-planar reconstruction images. Postoperative CT scan revealed fusion of the non-ossified segment of the OPLL was obtained in 4/23 patients (17%) in the LPM group and in 23/27 patients (85%) in the PDF group, showing a significant difference between both groups (p=0.003). Progression of the thickness of the OPLL in the PDF group (-0.1±0.4mm) was significantly smaller than in the LMP group (0.6±0.7mm, p=0.0002). The proportion of patients showing the decrease in thickness of OPLL was significantly larger in the PDF group (6/27 patients; 22%) than in the LMP group (0/23 patients; 0%, p=0.05). In conclusion, PDF surgery can suppress the thickening of OPLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain.

PubMed

Ladouceur, Alexandra; Rustamov, Nabi; Dubois, Jean-Daniel; Tessier, Jessica; Lehmann, Alexandre; Descarreaux, Martin; Rainville, Pierre; Piché, Mathieu

2017-10-10

The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p's <0.001), while selective attention only decreased pain (p < 0.01) and the N100 (p<0.001). In contrast, the P260 was decreased by HNCS only when attention was directed toward the HNCS stimulus (p<0.01). This indicates that patients with the characteristics described above do not show altered pain inhibitory mechanisms involved in HNCS and selective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Cohort study of cervical ossification of posterior longitudinal ligament in a Korean populations: Demographics of prevalence, surgical treatment, and disability.

PubMed

Shin, Jaeyong; Kim, Yong Wook; Lee, Sang Gyu; Park, Eun-Cheol; Yoon, Seo Yeon

2018-03-01

To investigate the demographic characteristics of cervical ossification of posterior longitudinal ligament (OPLL) including prevalence, surgical treatment, and disability in Korean population using Korean National Health Insurance Service National Sample Cohort (NHIS-NSC) data, and to analyze association between accessibility for surgical treatment and socioeconomic factors. A population-based cohort study was conducted using stratified representative sampling from NHIS-NSC data from the year 2002 to 2013. We analyzed prevalence and distribution of cervical OPLL according to age, sex, and socioeconomic factors. Multiple logistic regression analysis was conducted to investigate associations between independent variables and the rate of surgical treatment. The overall prevalence of cervical OPLL was 190 per 100,000 people in Korea, and 11.4% of male patients and 4.0% of female patients received surgical treatment. Logistic regression analysis revealed that male patients received more surgical treatment than did female patients, also income level and residential area influence the rate of surgical treatment in females after adjustment of covariates (p< 0.05). Disability rate associated with cervical OPLL was 2.27% in male and 0.99% in female patients. In this cohort study, the prevalence of cervical OPLL was 190 per 100,000 people. Male patients received more surgery, and disability rate of male was higher than female patients. Although surgical treatment is covered by medical insurance in Korea, socioeconomic factors such as income level and residential area influence the treatment plans in females. These findings can help in the understanding of disease progression and can inform surgical treatment plans to reduce disability. Copyright © 2018 Elsevier B.V. All rights reserved.

Recent research on the growth plate: Advances in fibroblast growth factor signaling in growth plate development and disorders.

PubMed

Xie, Yangli; Zhou, Siru; Chen, Hangang; Du, Xiaolan; Chen, Lin

2014-08-01

Skeletons are formed through two distinct developmental actions, intramembranous ossification and endochondral ossification. During embryonic development, most bone is formed by endochondral ossification. The growth plate is the developmental center for endochondral ossification. Multiple signaling pathways participate in the regulation of endochondral ossification. Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling has been found to play a vital role in the development and maintenance of growth plates. Missense mutations in FGFs and FGFRs can cause multiple genetic skeletal diseases with disordered endochondral ossification. Clarifying the molecular mechanisms of FGFs/FGFRs signaling in skeletal development and genetic skeletal diseases will have implications for the development of therapies for FGF-signaling-related skeletal dysplasias and growth plate injuries. In this review, we summarize the recent advances in elucidating the role of FGFs/FGFRs signaling in growth plate development, genetic skeletal disorders, and the promising therapies for those genetic skeletal diseases resulting from FGFs/FGFRs dysfunction. Finally, we also examine the potential important research in this field in the future. © 2014 Society for Endocrinology.

Organogenesis of the Musculoskeletal System in Horse Embryos and Early Fetuses.

PubMed

Barreto, Rodrigo da Silva Nunes; Rodrigues, Márcio Nogueira; Carvalho, Rafael Cardoso; De Oliveira E Silva, Fernanda Menezes; Rigoglio, Náthia Nathaly; Jacob, Júlio César Ferraz; Gastal, Eduardo Leite; Miglino, Maria Angélica

2016-06-01

Musculoskeletal system development involves heterotypical inductive interactions between tendons, muscles, and cartilage and knowledge on organogenesis is required for clarification of its function. The aim of this study was to describe the organogenesis of horse musculoskeletal system between 21 and 105 days of gestation, using detailed macroscopic and histological analyses focusing on essential developmental steps. At day 21 of gestation the skin was translucid, but epithelial condensation and fibrocartilaginous tissues were observed on day 25 of pregnancy. Smooth muscle was seen in lymphatic and blood vessel walls and the beginning of cartilaginous chondrocranium was detected at day 30 of gestation. At day 45, typical chondroblasts and chondrocytes were observed and at day 55, mandibular processes expanded toward the ventral midline of the pharynx. At day 75, muscles became thicker and muscle fibers were seen developing in carpal and metacarpal joints with the beginning of the ossification process. At day 105, major muscle groups, similar to those seen in an adult equine, were observed. The caudal area of the nasal capsule and trabecular cartilages increased in size and became ossified, developing into the ethmoid bone. The presence of nasal, frontal, parietal, and occipital bones was observed. In conclusion, novel features of equine musculoskeletal system development have been described here and each process was linked with an early musculoskeletal event. Data presented herein will facilitate a better understanding of the equine muscular system organogenesis and aid in the detection of congenital deformities. Anat Rec, 299:722-729, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Early Development and Orientation of the Acoustic Funnel Provides Insight into the Evolution of Sound Reception Pathways in Cetaceans

PubMed Central

Yamato, Maya; Pyenson, Nicholas D.

2015-01-01

Whales receive underwater sounds through a fundamentally different mechanism than their close terrestrial relatives. Instead of hearing through the ear canal, cetaceans hear through specialized fatty tissues leading to an evolutionarily novel feature: an acoustic funnel located anterior to the tympanic aperture. We traced the ontogenetic development of this feature in 56 fetal specimens from 10 different families of toothed (odontocete) and baleen (mysticete) whales, using X-ray computed tomography. We also charted ear ossification patterns through ontogeny to understand the impact of heterochronic developmental processes. We determined that the acoustic funnel arises from a prominent V-shaped structure established early in ontogeny, formed by the malleus and the goniale. In odontocetes, this V-formation develops into a cone-shaped funnel facing anteriorly, directly into intramandibular acoustic fats, which is likely functionally linked to the anterior orientation of sound reception in echolocation. In contrast, the acoustic funnel in balaenopterids rotates laterally, later in fetal development, consistent with a lateral sound reception pathway. Balaenids and several fossil mysticetes retain a somewhat anteriorly oriented acoustic funnel in the mature condition, indicating that a lateral sound reception pathway in balaenopterids may be a recent evolutionary innovation linked to specialized feeding modes, such as lunge-feeding. PMID:25760328

Origins of endothelial and osteogenic cells in the subcutaneous collagen gel implant.

PubMed

Bilic-Curcic, I; Kalajzic, Z; Wang, L; Rowe, D W

2005-11-01

The interdependent relationship between vascular endothelial cells and osteoblasts during bone formation and fracture healing has been long appreciated. This paper reports a heterotopic implant model using FGF-2-expanded bone marrow stromal cells (BMSC) derived from Tie2eGFP (endothelial marker) and pOBCol3.6GFPcyan or topaz (early osteoblast marker) transgenic mice to appreciate the host/donor relationships of cells participating in the process of heterotopic bone formation. The study included various combinations of Tie2eGFP and pOBCol3.6GFPcyan and topaz transgenics as BMSC or whole bone marrow (WBM) donors and also as recipients. Rat tail collagen was used as a carrier of donor cells and implantation was done in lethally irradiated mice rescued with WBM injection. Development of ossicles in the implants was followed weekly during the 4- to 5-week long post-implantation period. By 4-5 weeks after total body irradiation (TBI) and implantation, a well-formed bone spicule had developed that was invested with bone marrow. Experiments showed absolute dominance of donor-derived cells in the formation of endothelial-lined vessels inside the implants as well as the marrow stromal-derived osteogenic cells. Host-derived fibroblasts and osteogenic cells were confined to the fibrous capsule surrounding the implant. In addition, cells lining the endosteal surface of newly formed marrow space carrying a pOBCol3.6GFP marker were observed that were contributed by WBM donor cells and the host. Thus, FGF-2-expanded BMSC appear to be a source of endothelial and osteogenic progenitor cells capable of eliciting heterotopic bone formation independent of cells from the host. This model should be useful for understanding the interactions between these two cell types that control osteogenic differentiation in vivo.

Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle.

PubMed

Moore, Stephanie N; Hawley, Gregory D; Smith, Emily N; Mignemi, Nicholas A; Ihejirika, Rivka C; Yuasa, Masato; Cates, Justin M M; Liu, Xulei; Schoenecker, Jonathan G

2016-01-01

Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary to discriminate

Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle

PubMed Central

Moore, Stephanie N.; Hawley, Gregory D.; Smith, Emily N.; Mignemi, Nicholas A.; Ihejirika, Rivka C.; Yuasa, Masato; Cates, Justin M. M.; Liu, Xulei; Schoenecker, Jonathan G.

2016-01-01

Introduction Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Methods Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary

Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

PubMed Central

Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C

1991-01-01

With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7

The voluntary driven exoskeleton Hybrid Assistive Limb (HAL) for postoperative training of thoracic ossification of the posterior longitudinal ligament: a case report

PubMed Central

Abe, Tetsuya; Kubota, Shigeki; Marushima, Aiki; Kawamoto, Hiroaki; Ueno, Tomoyuki; Matsushita, Akira; Nakai, Kei; Saotome, Kosaku; Kadone, Hideki; Endo, Ayumu; Haginoya, Ayumu; Hada, Yasushi; Matsumura, Akira; Sankai, Yoshiyuki; Yamazaki, Masashi

2017-01-01

Context The hybrid assistive limb (HAL) is a wearable robot suit that assists in voluntary control of knee and hip joint motion by detecting bioelectric signals on the surface of the skin with high sensitivity. HAL has been reported to be effective for functional recovery in motor impairments. However, few reports have revealed the utility of HAL for patients who have undergone surgery for thoracic ossification of the posterior longitudinal ligament (thoracic OPLL). Herein, we present a postoperative thoracic OPLL patient who showed remarkable functional recovery after training with HAL. Findings A 63-year-old woman, who could not walk due to muscle weakness before surgery, underwent posterior decompression and fusion. Paralysis was re-aggravated after the initial postoperative rising. We diagnosed that paralysis was due to residual compression from the anterior lesion and microinstability after posterior fixation, and prescribed bed rest for a further 3 weeks. The incomplete paralysis gradually recovered, and walking training with HAL was started on postoperative day 44 in addition to standard physical therapy. The patient underwent 10 sessions of HAL training until discharge on postoperative day 73. Results of a 10-m walk test were assessed after every session, and the patient's speed and cadence markedly improved. At discharge, the patient could walk with 2 crutches and no assistance. Furthermore, no adverse events associated with HAL training occurred. Conclusion HAL training for postoperative thoracic OPLL patients may enhance improvement in walking ability, even if severe impairment of ambulation and muscle weakness exist preoperatively. PMID:26856189

Expansive open-door laminoplasty versus laminectomy and instrumented fusion for cases with cervical ossification of the posterior longitudinal ligament and straight lordosis.

PubMed

Liu, Xiaowei; Chen, Yu; Yang, Haisong; Li, Tiefeng; Xu, Bin; Chen, Deyu

2017-04-01

To identify whether expansive open-door laminoplasty (Lam) is more appropriate than laminectomy and instrumented fusion (LIF) for cases with ossification of the posterior longitudinal ligament (OPLL) and straight cervical lordosis. A total of 67 cases were included and divided into Group Lam (n = 32) and Group LIF (n = 35), and the mean follow-up periods were 38 and 42 months, respectively. The cervical lordosis was elevated by C2-7 Cobb angle and cervical sagittal balance by C2-C7 sagittal vertical axis (SVA). Japanese Orthopedic Association (JOA), neurological recovery rate (RR) being calculated by the JOA, visual analog scale (VAS) and neck disability index (NDI) were used to assess clinical outcomes. Differences in general data between two groups were not significant. Total blood loss and operation duration in Group Lam were both significantly less than that in the Group LIF. By the final follow-up, the cervical lordosis significantly decreased in Group Lam and increased in Group LIF, the SVA significantly increased in Group Lam and kept unchanged in Group LIF, and the JOA, VAS, NDI significantly improved in both groups. Although there was no significant difference in RR between the two groups, cases in Group Lam had significantly larger incidence of postoperative kyphosis and kyphotic change rate, and less VAS, NDI and incidence of axial pain than cases in Group LIF. When compared with the LIF, the Lam is recommended for cases with OPLL and straight cervical lordosis when taking comparable neurological recovery, less axial pain and better neck function improvement into consideration.

Radiographic predictors for the development of myelopathy in patients with ossification of the posterior longitudinal ligament: a multicenter cohort study.

PubMed

Matsunaga, Shunji; Nakamura, Kozo; Seichi, Atsushi; Yokoyama, Toru; Toh, Satoshi; Ichimura, Shoichi; Satomi, Kazuhiko; Endo, Kenji; Yamamoto, Kengo; Kato, Yoshiharu; Ito, Tatsuo; Tokuhashi, Yasuaki; Uchida, Kenzo; Baba, Hisatoshi; Kawahara, Norio; Tomita, Katsuro; Matsuyama, Yukihiro; Ishiguro, Naoki; Iwasaki, Motoki; Yoshikawa, Hideki; Yonenobu, Kazuo; Kawakami, Mamoru; Yoshida, Munehito; Inoue, Shinsuke; Tani, Toshikazu; Kaneko, Kazuo; Taguchi, Toshihiko; Imakiire, Takanori; Komiya, Setsuro

2008-11-15

A multicenter cohort study was performed retrospectively. To identify radiographic predictors for the development of myelopathy in patients with ossification of the posterior longitudinal ligaments (OPLL). The pathomechanism of myelopathy in the OPLL remains unknown. Some patients with large OPLL have not exhibited myelopathy for a long periods of time. Predicting the course of future neurologic deterioration in asyptomatic patients with OPLL is difficult at their initial visit. A total of 156 OPLL patients from 16 spine institutes with an average of 10.3 years of follow-up were reviewed. Subjects underwent a plain roentgenogram, computed tomography (CT), and magnetic resonance imaging of the cervical spine during the follow-up. The trauma history of the cervical spine, maximum percentage of spinal canal stenosis in a plain roentgenogram and CT, range of motion of the cervical spine, and axial ossified pattern in magnetic resonance imaging or CT were reviewed in relation to the existence of myelopathy. All 39 patients with greater than 60% spinal canal stenosis on the plain roentgenogram exhibited myelopathy. Of 117 patients with less than 60% spinal canal stenosis, 57 (49%) patients exhibited myelopathy. The range of motion of the cervical spine was significantly larger in patients with myelopathy than in those of without it. The axial ossified pattern could be classified into 2 types: a central type and a lateral deviated type. The incidence of myelopathy in patients with less than 60% spinal canal stenosis was significantly higher in the lateral deviated-type group than in the central-type group. Fifteen patients of 156 subjects developed trauma-induced myelopathy. Of the 15 patients, 13 had mixed-type OPLL and 2 had segmental-type OPLL. Static and dynamic factors were related to the development of myelopathy in OPLL.

Spongiosa Primary Development: A Biochemical Hypothesis by Turing Patterns Formations

PubMed Central

López-Vaca, Oscar Rodrigo; Garzón-Alvarado, Diego Alexander

2012-01-01

We propose a biochemical model describing the formation of primary spongiosa architecture through a bioregulatory model by metalloproteinase 13 (MMP13) and vascular endothelial growth factor (VEGF). It is assumed that MMP13 regulates cartilage degradation and the VEGF allows vascularization and advances in the ossification front through the presence of osteoblasts. The coupling of this set of molecules is represented by reaction-diffusion equations with parameters in the Turing space, creating a stable spatiotemporal pattern that leads to the formation of the trabeculae present in the spongy tissue. Experimental evidence has shown that the MMP13 regulates VEGF formation, and it is assumed that VEGF negatively regulates MMP13 formation. Thus, the patterns obtained by ossification may represent the primary spongiosa formation during endochondral ossification. Moreover, for the numerical solution, we used the finite element method with the Newton-Raphson method to approximate partial differential nonlinear equations. Ossification patterns obtained may represent the primary spongiosa formation during endochondral ossification. PMID:23193429

Differential inhibitory effect on human nociceptive skin senses induced by local stimulation of thin cutaneous fibers.

PubMed

Nilsson, H J; Schouenborg, J

1999-03-01

It is known that stimulation of thin cutaneous nerve fibers can induce long lasting analgesia through both supraspinal and segmental mechanisms, the latter often exhibiting restricted receptive fields. On this basis, we recently developed a new method, termed cutaneous field stimulation (CFS), for localized stimulation of A delta and C fibers in the superficial part of the skin. In the present study, we have evaluated the effects of CFS on non-nociceptive and nociceptive skin senses. We compared the effects of CFS with those of conventional transcutaneous electrical nerve stimulation (TENS), known to preferentially activate coarse myelinated fibers. A battery of sensory tests were made on the right volar forearm of 20 healthy subjects. CFS (16 electrodes, 4 Hz per electrode, 1 ms, up to 0.8 mA) and TENS (100 Hz, 0.2 ms, up to 26 mA) applied either on the right volar forearm (homotopically), or on the lower right leg (heterotopically) were used as conditioning stimulation for 25 min. The tactile threshold was not affected by either homo- or heterotopical CFS or TENS. The mean thresholds for detecting warming or cooling of the skin were increased by 0.4-0.9 degrees C after homo- but not heterotopical CFS and TENS. Regarding nociceptive skin senses, homo- but not heterotopical CFS, markedly reduced CO2-laser evoked A delta- and C fiber mediated heat pain to 75 and 48% of control, respectively, and mechanically evoked pain to 73% of control. Fabric evoked prickle, was not affected by CFS. Neither homo- nor heterotopical TENS induced any marked analgesic effects. It is concluded that different qualities of nociception can be differentially controlled by CFS.

Incarcerated medial epicondyle fracture following pediatric elbow dislocation: 11 cases.

PubMed

Dodds, Seth D; Flanagin, Brody A; Bohl, Daniel D; DeLuca, Peter A; Smith, Brian G

2014-09-01

To describe outcomes after surgical management of pediatric elbow dislocation with incarceration of the medial epicondyle. We conducted a retrospective case review of 11 consecutive children and adolescents with an incarcerated medial epicondyle fracture after elbow dislocation. All patients underwent open reduction internal fixation using a similar technique. We characterized outcomes at final follow-up. Average follow-up was 14 months (range, 4-56 mo). All patients had clinical and radiographic signs of healing at final follow-up. There was no radiographic evidence of loss of reduction at intervals or at final follow-up. There were no cases of residual deformity or valgus instability. Average final arc of elbow motion was 4° to 140°. All patients had forearm rotation from 90° supination to 90° pronation. Average Mayo elbow score was 99.5. Four of 11 patients had ulnar nerve symptoms postoperatively and 1 required a second operation for ulnar nerve symptoms. In addition, 1 required a second operation for flexion contracture release with excision of heterotopic ossification. Three patients had ulnar nerve symptoms at final follow-up. Two of these had mild paresthesia only and 1 had both mild paresthesia and weakness. Our results suggest that open reduction internal fixation of incarcerated medial epicondyle fractures after elbow dislocation leads to satisfactory motion and function; however, the injury carries a high risk for complications, particularly ulnar neuropathy. Therapeutic IV. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

INFIX versus plating for pelvic fractures with disruption of the symphysis pubis.

PubMed

Vaidya, Rahul; Martin, Adam Jonathan; Roth, Matthew; Nasr, Kerellos; Gheraibeh, Petra; Tonnos, Frederick

2017-08-01

The purpose of this study is to compare INFIX to plating in the treatment of unstable pelvic ring injuries with disruption of the symphysis. Twenty-four patients treated with INFIX were compared to 28 patients fixed by plating. All patients had anterior and posterior fixation. Injuries were classified using the Young and Burgess and AO/OTA classification systems. Reductions of the pelvic ring were assessed using the pelvic deformity index (PDI) and symphyseal widening. Patients were contacted to get functional outcomes using the Majeed scoring system and complications were tabulated . INFIX was inferior to plating at reducing symphyseal widening (INFIX 10.72± 5.0 Plates 6.97 ± 3.39 P = 0.012) but similar in reducing the pelvic deformity index. (INFIX 0.0221± .015 Plates 0.0190 ± .0105 P = 0 .38). Majeed scores were similar 83.95 ± 15.2 (median 89, range 51-100) for INFIX and 77.67± 16.7 (median 79, range 54-100) for plating. Complications included infection (1 (4%) INFIX , 4 (14%) plates), improper hardware placement or failure (2 (8%) INFIX, 3 (11%) plates), and heterotopic ossification (11 (46%) INFIX, 16 (57.1%) plates). Infection in the plated patients was related to urological injury in 3/4 cases. Plating provides better reduction of the pubic symphysis and requires only one surgery. Outcomes scores were similar. INFIX may be preferable in obese patients, young women of childbearing age or those with urological injury.

[A primary application and evaluation of temporomandibular joint replacement with stock prosthesis].

PubMed

Zhang, Xiao-hu; Chen, Min-jie; Qiu, Ya-ting; Yang, Chi

2012-06-01

To evaluate the effect of total joint replacement in treatment of temporomandibular joint(TMJ) osteoarthropathy with stock prostheses. Six female patients involving 10 joints (2 unilateral and 4 bilateral), with an average age of 59 years old, were involved in this study. Three patients (5 joints) were diagnosed as internal derangement in V stage depending on MRI, 3D-CT findings and clinical characteristics. The other 3 patients (5 joints) had histories of failed temporomandibular joint operation using costochondral graft or temporalis fascial flap. The maximal mouth opening was 1.9 cm on average (range, 1.0 to 2.9cm). All the joints were replaced with Biomet standard prosthesis under general anesthesia. The follow-up period was from 7 to 49 months (average, 17.5 months). All the operations were successfully performed. Heterotopic ossification happened in a bilateral case 1 year postoperatively. One patient with bilateral joint disease complained of severe uncomfortable feeling in the region of the ears and the temples, although there was no significant positive signs according to an ENT examination. Pain relief of the joint and mouth opening improvement were significant in 4 patients. No failure was noted secondary to infection or loosening of the prostheses. The occlusal relationship kept stable postoperatively in all cases. Total TMJ joint replacement with standard prosthesis is a good choice for TMJ reconstruction. It can significantly reduce joint pain and the mouth opening limitation resulted from osteoarthritis. Long-term result remains to be evaluated based on a long-term follow-up.

Reverse shoulder arthroplasty for massive irreparable rotator cuff tears and cuff tear arthropathy: a systematic review.

PubMed

Petrillo, S; Longo, U G; Papalia, R; Denaro, V

2017-08-01

To report the outcomes and complications of reverse shoulder arthroplasty (RSA) in massive irreparable rotator cuff tears (MIRCT) and cuff tear arthropathy (CTA). A systematic review of the literature contained in Medline, Cochrane, EMBASE, Google Scholar and Ovid databases was conducted on May 1, 2016, according to PRISMA guidelines. The key words "reverse total shoulder arthroplasty" or "reverse total shoulder prostheses" with "rotator cuff tears"; "failed rotator cuff surgery"; "massive rotator cuff tears"; "irreparable rotator cuff tears"; "cuff tear arthropathy"; "outcomes"; "complications" were matched. All articles reporting outcomes and complications of RSA for the management of MIRCT or CTA were included. The comparison between preoperative and postoperative clinical scores, as well as range of motion (ROM), was performed using the Wilcoxon-Mann-Whitney test. P values lower than 0.05 were considered statistically significant. Seven articles were included in our qualitative synthesis. A statistically significant improvement in all clinical scores and ROM was found comparing the preoperative value with the postoperative value. The degrees of retroversion of the humeral stem of the RSA do not influence the functional outcomes in a statistically significant fashion. There were 17.4% of complications. The most frequent was heterotopic ossification, occurring in 6.6% of patients. Revision surgery was necessary in 7.3% of patients. RSA restores pain-free ROM and improves function of the shoulder in patients with MIRCT or CTA. However, complications occur in a high percentage of patients. The lack of level I studies limits the real understanding of the potentials and limitations of RSA for the management of MIRCT and CTA.

Postoperative Complications Associated With rhBMP2 Use in Posterior/Posterolateral Lumbar Fusion.

PubMed

Esmail, Nabil; Buser, Zorica; Cohen, Jeremiah R; Brodke, Darrel S; Meisel, Hans-Joerg; Park, Jong-Beom; Youssef, Jim A; Wang, Jeffrey C; Yoon, S Tim

2018-04-01

Retrospective database review. Posterior/posterolateral lumbar fusion (PLF) is an effective treatment for a variety of spinal disorders; however, variations in surgical technique have different complication profiles. The aim of our study was to quantify the frequency of various complications in patients undergoing PLF with and without human recombinant bone morphogenetic protein 2 (rhBMP2). We queried the orthopedic subset of the Medicare database (PearlDiver) between 2005 and 2011 for patients undergoing PLF procedures with and without rhBMP2. Complication and reoperation rates were analyzed within 1 year of the index procedure. Complications assessed include: acute renal failure, deep vein thrombosis, dural tear, hematoma, heterotopic ossification, incision and drainage, cardiac complications, nervous system complications, osteolysis, pneumonia, pseudarthrosis, pulmonary embolism, radiculopathy, respiratory complications, sepsis, urinary retention, urinary tract infection, mechanical, and wound complications. Chi-square analysis was used to calculate the complication differences between the groups. Our data revealed higher overall complication rates in patients undergoing PLF with rhBMP2 versus no_rhBMP2 (76.9% vs 68.8%, P < .05). Stratified by gender, rhBMP2 males had higher rates of mechanical complications, pseudarthrosis, and reoperations compared with no_rhBMP2 males ( P < .05), whereas rhBMP2 females had higher rates of pseudarthrosis, urinary tract infection, and urinary retention compared with no_rhBMP2 females ( P < .05). Our data revealed higher overall complication rates in PLF patients given rhBMP2 compared with no_rhBMP2. Furthermore, our data suggests that rhBMP2-associated complications may be gender specific.

Clinical and Radiographic Outcomes of Unipolar and Bipolar Radial Head Prosthesis in Patients with Radial Head Fracture: A Systemic Review and Meta-Analysis.

PubMed

Chen, Hongwei; Wang, Ziyang; Shang, Yongjun

2018-06-01

To compare clinical outcomes of unipolar and bipolar radial head prosthesis in the treatment of patients with radial head fracture. Medline, Cochrane, EMBASE, Google Scholar databases were searched until April 18, 2016 using the following search terms: radial head fracture, elbow fracture, radial head arthroplasty, implants, prosthesis, unipolar, bipolar, cemented, and press-fit. Randomized controlled trials, retrospective, and cohort studies were included. The Mayo elbow performance score (MEPS), disabilities of the arm, shoulder, and hand (DASH) score, radiologic assessment, ROM, and grip strength following elbow replacement were similar between prosthetic devices. The pooled mean excellent/good ranking of MEPS was 0.78 for unipolar and 0.73 for bipolar radial head arthroplasty, and the pooled mean MEPS was 86.9 and 79.9, respectively. DASH scores for unipolar and bipolar prosthesis were 19.0 and 16.3, respectively. Range of motion outcomes were similar between groups, with both groups have comparable risk of flexion arc, flexion, extension deficit, rotation arc, pronation, and supination (p values <0.001 for both unipolar and bipolar prosthesis). However, bipolar radial head prosthesis was associated with an increased chance of heterotopic ossification and lucency (p values ≤0.049) while unipolar prosthesis was not (p values ≥0.088). Both groups had risk for development of capitellar osteopenia or erosion/wear (p values ≤0.039). Unipolar and bipolar radial head prostheses were similar with respect to clinical outcomes. Additional comparative studies are necessary to further compare different radial head prostheses used to treat radial head fracture.

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

PubMed Central

Hatfield, Paul; Prestwich, Robin JD; Shaffer, Richard E; Taylor, Roger E

2015-01-01

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren's disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children. PMID:26462717

Facies architecture and paleohydrology of a synrift succession in the Early Cretaceous Choyr Basin, southeastern Mongolia

USGS Publications Warehouse

Ito, M.; Matsukawa, M.; Saito, T.; Nichols, D.J.

2006-01-01

The Choyr Basin is one of several Early Cretaceous rift basins in southwestern Mongolia that developed in specific regions between north-south trending fold-and-thrust belts. The eastern margin of the basin is defined by high-angle normal and/or strike-slip faults that trend north-to-south and northeast-to-southwest and by the overall geometry of the basin, which is interpreted to be a half graben. The sedimentary succession of the Choyr Basin documents one of the various types of tectono-sedimentary processes that were active in the rift basins of East Asia during Early Cretaceous time. The sedimentary infill of the Choyr Basin is newly defined as the Khalzan Uul and Khuren Dukh formations based on detailed mapping of lateral and vertical variations in component lithofacies assemblages. These two formations are heterotopic deposits and constitute a third-order fluvio-lacustrine sequence that can be divided into transgressive and highstand systems tracts. The lower part of the transgressive systems tract (TST) is characterized by sandy alluvial-fan and braided-river systems on the hanging wall along the western basin margin, and by a gravelly alluvial-fan system on the footwall along the eastern basin margin. The alluvial-fan and braided-river deposits along the western basin margin are fossiliferous and are interpreted to have developed in association with a perennial fluvial system. In contrast, alluvial-fan deposits along the eastern basin margin do not contain any distinct faunas or floras and are interpreted to have been influenced by a high-discharge ephemeral fluvial system associated with fluctuations in wetting and drying paleohydrologic processes. The lower part of the TST deposit fines upward to siltstone-dominated flood-plain and ephemeral-lake deposits that constitute the upper part of the TST and the lower part of the highstand systems tract (HST). These mudstone deposits eventually reduced the topographic irregularities typical of the early stage of

Intermediate clinical and radiological results of cervical TDR (Mobi-C®) with up to 2 years of follow-up

PubMed Central

Beaurain, J.; Bernard, P.; Dufour, T.; Fuentes, J. M.; Hovorka, I.; Huppert, J.; Steib, J. P.; Vital, J. M.; Aubourg, L.

2009-01-01

The interest in cervical total disc replacement (TDR) as an alternative to the so-far gold standard in the surgical treatment of degenerative disc disease (DDD), e.g anterior cervical discectomy and fusion (ACDF), is growing very rapidly. Many authors have established the fact that ACDF may result in progressive degeneration in adjacent segments. On the contrary, but still theoretically, preservation of motion with TDR at the surgically treated level may potentially reduce the occurrence of adjacent-level degeneration (ALD). The authors report the intermediate results of an undergoing multicentre prospective study of TDR with Mobi-C® prosthesis. The aim of the study was to assess the safety and efficacy of the device in the treatment of DDD and secondary to evaluate the radiological status of adjacent levels and the occurrence of ossifications, at 2-year follow-up (FU). 76 patients have performed their 2-year FU visit and have been analyzed clinically and radiologically. Clinical outcomes (NDI, VAS, SF-36) and ROM measurements were analyzed pre-operatively and at the different post-operative time-points. Complications and re-operations were also assessed. Occurrences of heterotopic ossifications (HOs) and of adjacent disc degeneration radiographic changes have been analyzed from 2-year FU X-rays. The mean NDI and VAS scores for arm and neck are reduced significantly at each post-operative time-point compared to pre-operative condition. Motion is preserved over the time at index levels (mean ROM = 9° at 2 years) and 85.5% of the segments are mobile at 2 years. HOs are responsible for the fusion of 6/76 levels at 2 years. However, presence of HO does not alter the clinical outcomes. The occurrence rate of radiological signs of ALD is very low at 2 years (9.1%). There has been no subsidence, no expulsion and no sub-luxation of the implant. Finally, after 2 years, 91% of the patients assume that they would undergo the procedure again. These intermediate

Thumb Ossification Composite Index (TOCI) for Predicting Peripubertal Skeletal Maturity and Peak Height Velocity in Idiopathic Scoliosis: A Validation Study of Premenarchal Girls with Adolescent Idiopathic Scoliosis Followed Longitudinally Until Skeletal Maturity.

PubMed

Hung, Alec L H; Chau, W W; Shi, B; Chow, Simon K; Yu, Fiona Y P; Lam, T P; Ng, Bobby K W; Qiu, Y; Cheng, Jack C Y

2017-09-06

Accurate skeletal maturity assessment is important to guide clinical evaluation of idiopathic scoliosis, but commonly used methods are inadequate or too complex for rapid clinical use. The objective of the study was to propose a new simplified staging method, called the thumb ossification composite index (TOCI), based on the ossification pattern of the 2 thumb epiphyses and the adductor sesamoid bone; to determine its accuracy in predicting skeletal maturation when compared with the Sanders simplified skeletal maturity system (SSMS); and to validate its interrater and intrarater reliability. Hand radiographs of 125 girls, acquired when they were newly diagnosed with idiopathic scoliosis prior to menarche and during longitudinal follow-up until skeletal maturity (a minimum of 4 years), were scored with the TOCI and SSMS. These scores were compared with digital skeletal age (DSA) and radius, ulna, and small hand bones (RUS) scores; anthropometric data; peak height velocity; and growth-remaining profiles. Correlations were analyzed with the chi-square test, Spearman and Cramer V correlation methods, and receiver operating characteristic curve analysis. Reliability analysis using the intraclass correlation (ICC) was conducted. Six hundred and forty-five hand radiographs (average, 5 of each girl) were scored. The TOCI staging system was highly correlated with the DSA and RUS scores (r = 0.93 and 0.92, p < 0.01). The mean peak height velocity (and standard deviation) was 7.43 ± 1.45 cm/yr and occurred at a mean age of 11.9 ± 0.86 years, with 70.1% and 51.4% of the subjects attaining their peak height velocity at TOCI stage 5 and SSMS stage 3, respectively. The 2 systems predicted peak height velocity with comparable accuracy, with a strong Cramer V association (0.526 and 0.466, respectively; p < 0.01) and similar sensitivity and specificity on receiver operating characteristic curve analysis. The mean age at menarche was 12.57 ± 1.12 years, with menarche occurring

Periacetabular osteotomy and combined femoral head-neck junction osteochondroplasty: a minimum two-year follow-up cohort study.

PubMed

Nassif, Nader A; Schoenecker, Perry L; Thorsness, Robert; Clohisy, John C

2012-11-07

Proximal femoral deformities and overcorrection of the acetabulum both can result in secondary femoroacetabular impingement and suboptimal clinical results after periacetabular osteotomy. The purpose of the present study was to determine the rate of complications, the need for reoperations, radiographic correction, and hip function among patients who underwent periacetabular osteotomy and combined femoral head-neck osteochondroplasty as compared with those who underwent periacetabular osteotomy alone. Patients who underwent periacetabular osteotomy with or without osteochondroplasty of the femoral head-neck junction were evaluated retrospectively after a minimum duration of follow-up of two years. We compared the two groups with regard to the modified Harris hip score, radiographic correction, complications, and reoperations. Forty patients (forty hips) who underwent periacetabular osteotomy in conjunction with a femoral head-neck osteochondroplasty were compared with forty-eight patients (forty-eight hips) who underwent an isolated periacetabular osteotomy. Patients were evaluated after a mean duration of follow-up of 3.4 years (range, 2.0 to 9.7 years). Preoperatively, the modified Harris hip score (and standard deviation) was 64.3 ± 13.2 for the study group and 63.2 ± 13.4 for the comparison group. At the time of the latest follow-up, the modified Harris hip score was not significantly different between the study group and the comparison group (p = 0.17). Patients demonstrated equivalent preoperative deformities and postoperative acetabular radiographic parameters. There was a significant decrease in the alpha angle and improvement in head-neck offset in the study group. There was one reoperation for secondary impingement and/or labral pathology in the study group, compared with four reoperations in the comparison group. There were no adhesions requiring surgery, femoral neck fractures, instances of osteonecrosis, or increases in heterotopic ossification in

Fetal and Early Post-Natal Mineralization of the Tympanic Bulla in Fin Whales May Reveal a Hitherto Undiscovered Evolutionary Trait

PubMed Central

Cozzi, Bruno; Podestà, Michela; Mazzariol, Sandro; Zotti, Alessandro

2012-01-01

The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival. PMID:22615912

Diffusion Tensor Imaging of Heterotopia: Changes of Fractional Anisotropy during Radial Migration of Neurons

PubMed Central

Kim, Jinna

2010-01-01

Purpose Diffusion tensor imaging provides better understanding of pathophysiology of congenital anomalies, involving central nervous system. This study was aimed to specify the pathogenetic mechanism of heterotopia, proved by diffusion tensor imaging, and establish new findings of heterotopia on fractional anisotropy maps. Materials and Methods Diffusion-weighted imaging data from 11 patients (M : F = 7 : 4, aged from 1 to 22 years, mean = 12.3 years) who visited the epilepsy clinic and received a routine seizure protocol MRI exam were retrospectively analyzed. Fractional anisotropy (FA) maps were generated from diffusion tensor imaging of 11 patients with heterotopia. Regions of interests (ROI) were placed in cerebral cortex, heterotopic gray matter and deep gray matter, including putamen. ANOVA analysis was performed for comparison of different gray matter tissues. Results Heterotopic gray matter showed signal intensities similar to normal gray matter on T1 and T2 weighted MRI. The measured FA of heterotopic gray matter was higher than that of cortical gray matter (0.236 ± 0.011 vs. 0.169 ± 0.015, p < 0.01, one way ANOVA), and slightly lower than that of deep gray matter (0.236 ± 0.011 vs. 0.259 ± 0.016, p < 0.01). Conclusion Increased FA of heterotopic gray matter suggests arrested neuron during radial migration and provides better understanding of neurodevelopment. PMID:20499428

[Pregnancy in rudimentary uterine horn: diagnostic and therapeutic difficulties].

PubMed

Sefrioui, O; Azyez, M; Babahabib, A; Kaanane, F; Matar, N

2004-04-01

Ectopic pregnancy in a rudimentary uterine horn is extremely uncommon. Implantation of one embryo in the uterine cavity and of another in a rudimentary uterine horn is an extremely uncommon form of twin pregnancy. The authors report three cases of pregnancies in a rudimentary uterine horn. One was associated to a heterotopic pregnancy in the other eutrophic horn. Through these three cases, they report the risks incurred and the difficulties of the assumption of responsibility of this type of pathology, on the diagnostic as well as therapeutic level. But generally underline the interest of echography especially endovaginale and the coelioscopy in the early diagnosis of this type of uterine malformation.

Comparison of clinical outcomes between laminoplasty, posterior decompression with instrumented fusion, and anterior decompression with fusion for K-line (-) cervical ossification of the posterior longitudinal ligament.

PubMed

Koda, Masao; Mochizuki, Makondo; Konishi, Hiroaki; Aiba, Atsuomi; Kadota, Ryo; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Mannoji, Chikato; Furuya, Takeo

2016-07-01

The K-line, which is a virtual line that connects the midpoints of the anteroposterior diameter of the spinal canal at C2 and C7 in a plain lateral radiogram, is a useful preoperative predictive indicator for sufficient decompression by laminoplasty (LMP) for ossification of the posterior longitudinal ligament (OPLL). K-line is defined as (+) when the peak of OPLL does not exceed the K-line, and is defined as (-) when the peak of OPLL exceeds the K-line. For patients with K-line (-) OPLL, LMP often results in poor outcome. The aim of the present study was to compare the clinical outcome of LMP, posterior decompression with instrumented fusion (PDF) and anterior decompression and fusion (ADF) for patients with K-line (-) OPLL. The present study included patients who underwent surgical treatment including LMP, PDF and ADF for K-line (-) cervical OPLL. We retrospectively compared the clinical outcome of those patients in terms of Japanese Orthopedic Association score (JOA score) recovery rate. JOA score recovery rate was significantly higher in the ADF group compared with that in the LMP group and the PDF group. The JOA score recovery rate in the PDF group was significantly higher than that in the LMP group. LMP should not be used for K-line (-) cervical OPLL. ADF is one of the suitable surgical treatments for K-line (-) OPLL. Both ADF and PDF are applicable for K-line (-) OPLL according to indications set by each institute and surgical decisions.

Osteochondrosis dissecans of the elbow.

PubMed

Van Sonhoven, F; Geusens, E; Nijs, S

2009-01-01

This case shows a typical presentation of an osteochondrosis dissecans lesion on the capitellum, with associated intra-articular loose bodie(s), diagnosed on plain film. Osteochondrosis dissecans (OCD) is a rather common entity. Mostly the knee joint is involved. Only 5% of OCD lesions occur in the elbow joint. Possible causes of osteochondrosis dissecans include (repetitive) trauma (e.g. in throwing sports or gymnastics), ischemia, ossification defects, and genetic factors. Conventional radiography mostly has a low sensitivity to detect OCD lesions, and is often normal in early stages. CT is more sensitive to detect intra-articular loose bodies. MRI detects very early stages of OCD and radiographically occult lesions that may not be evident on CT.

Growth of severely hypoplastic phalanges and metacarpals in symbrachydactyly: an experimental study in mice.

PubMed

Kanauchi, Yumiko; Takahara, Masatoshi; Harada, Mikio; Ogino, Toshihiko

2008-11-01

Severely hypoplastic phalanges and metacarpals in symbrachydactyly are often associated with a delay or failure of primary ossification evident by radiography at birth. However, little is known about the ossification pattern and further growth of severely hypoplastic bones in symbrachydactyly. To clarify this mechanism, we observed development during ossification of the hypoplastic phalanges in brachypodism mice (which carry functional null mutations of growth differentiation factor 5 and exhibit hypoplastic phalanges) as a model of the bone hypoplasia in symbrachydactyly. Forelimbs of wild-type and brachypodism mice from embryonic day 16.5 to 21 days after birth were sectioned. We used radiography to examine the progression of ossification; safranin O fast green-iron hematoxylin staining and in situ hybridization for type II collagen to demonstrate cartilage; the transferase-mediated nick end-labeling assay to identify apoptosis; and tartrate-resistant acid phosphatase staining to demonstrate osteoclastic activity. In brachypodism mice, radiography showed markedly delayed ossification of the proximal phalanges in comparison with wild-type mice. Safranin O staining and type II collagen in situ hybridization showed that the cartilage anlagen of the proximal phalanges were extremely small, with diffuse endochondral ossification throughout, resulting in lack of growth plate and chondroepiphysis formation. Apoptotic cells were present under the perichondrium on the plantar side of the proximal phalanges from day 7 after birth and had spread randomly by day 14. Diffuse osteoclastic activity was evident throughout the proximal phalanges from days 7 to 14 after birth. These results indicate that severely hypoplastic proximal phalanges in brachypodism mice, although showing an endochondral ossification pattern, lack a growth plate and have no potential for secondary growth. These findings may be relevant to the treatment of symbrachydactyly with severely hypoplastic bones

Middle ear bones of a mid-gestation ruminant foetus extracted from x-ray computed tomography

NASA Astrophysics Data System (ADS)

Costeur, Loic; Mennecart, Bastien; Müller, Bert; Schulz, Georg

2016-10-01

The timing of ossification of middle ear ossicles has been extensively studied in humans. This is an exception since it is vastly unknown in the +5000 extant species of placentals. As a preliminary approach, a cow foetus (around 115 days of gestation) was visualized using X-ray microtomography (μCT) and the ossicles including stapes, incus, and malleus could be extracted from the data set. All three bones have already undergone substantial ossification, which allow comparison to adult middle ear bones. Their ossification at this stage parallels ossification in humans at a comparable stage of gestation. While full ossification is not yet achieved almost all the morphological characters of the ossicles are observed. Bone tissue is still very porous, the stapes does not have the characteristic plate-like footplate, the lenticular process of the incus is missing and the manubrium of the malleus is very thin and not yet complete. Despite all this, the ossicles are articulate with each other and perfectly with the bony labyrinth. The stapes footplate is positioned on the oval window but is smaller than the latter while it should perfectly fit to transmit sound vibrations to the cochlea. All ossicles, especially the stapes, have not yet reached adult size, while the bony labyrinth already has. This is the first detailed description of a set of middle ear bones in a placental at mid-gestation based on high-resolution μCT. Similarities in ossification timing with humans encourage more work to be done on foetuses to understand if a general rule for placental mammals exists.

A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia.

PubMed

Özgün, Gonca; Adim, Şaduman Balaban; Uğraş, Nesrin; Kiliçturgay, Sadık

2017-01-01

Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

The role of oxygen as a regulator of stem cell fate during fracture repair in TSP2-null mice.

PubMed

Burke, Darren; Dishowitz, Michael; Sweetwyne, Mariya; Miedel, Emily; Hankenson, Kurt D; Kelly, Daniel J

2013-10-01

It is often difficult to decouple the relative importance of different factors in regulating MSC differentiation. Genetically modified mice provide model systems whereby some variables can be manipulated while others are kept constant. Fracture repair in thrombospondin-2 (TSP2)-null mice is characterized by reduced endochondral ossification and enhanced intramembranous bone formation. The proposed mechanism for this shift in MSC fate is that increased vascular density and hence oxygen availability in TSP2-null mice regulates differentiation. However, TSP2 is multifunctional and regulates other aspects of the regenerative cascade, such as MSC proliferation. The objective of this study is to use a previously developed computational model of tissue differentiation, in which substrate stiffness and oxygen tension regulate stem cell differentiation, to simulate potential mechanisms which may drive alterations in MSC fate in TSP2-null mice. Four models (increased cell proliferation, increased numbers of MSCs in the marrow decreased cellular oxygen consumption, and an initially stiffer callus) were not predictive of experimental observations in TSP2-null mice. In contrast, increasing the rate of angiogenic progression led to a prediction of greater intramembranous ossification, diminished endochondral ossification, and a reduced region of hypoxia in the fracture callus similar to that quantified experimentally by the immunohistochemical detection of pimonidazole adducts that develop with hypoxia. This study therefore provides further support for the hypothesis that oxygen availability during early fracture healing is a key regulator of MSC bipotential differentiation, and furthermore, it highlights the advantages of integrating computational models with genetically modified mouse studies for further elucidating mechanisms regulating stem cell fate. Copyright © 2013 Orthopaedic Research Society.

Outcomes, and factors affecting outcomes, following shoulder hemiarthroplasty for proximal humeral fracture repair.

PubMed

Liu, Jie; Li, Shao-Hua; Cai, Zheng-Dong; Lou, Lie-Ming; Wu, Xing; Zhu, Yu-Chang; Wu, Wei-Ping

2011-09-01

Hemiarthroplasty has been applied to treat proximal humeral fracture with variable outcomes. The purpose of this retrospective study was to assess factors affecting outcome in patients following hemiarthroplasty for proximal humeral fracture (PHF) repair. Patients with proximal humeral fractures treated over a 6-year period were included. Indications for hemiarthroplasty were severe three-part fractures associated with osteoporosis; four-part fractures with or without dislocation; splitting of the humeral head, or >45% collapse of the humeral head. Surgery outcome and postoperative complications were main outcome measures in this study. Thirty-three of 47 patients were included in the final analysis (mean age 64.3 years, range 43-82). Mean postoperative follow-up was 44.4 (range 36-57) months. Postoperative complications (shoulder dislocation, mild shoulder subluxation, heterotopic ossification) occurred in seven patients. Healing of the greater and lesser tubercles was abnormal or poor in 18 patients. These patients had significantly higher pain scores (4.0 ± 1.1 vs. 2.2 ± 1.1) and significantly lower capacities for active lifting (79.3 ± 9.6 vs. 121.7 ± 24.3), external rotation (20.7 ± 3.7 vs. 39.2 ± 10.3), and Neer scores (79.2 ± 5.7 vs. 90.6 ± 3.6) versus patients who exhibited complete healing (all P < 0.001). Patient age, type of surgical approach, and fracture type were not major influencers of outcome. In conclusion, the healing of the greater and lesser tubercles is the major determinant of outcome following hemiarthroplasty for PHF repair.

Elbow hemiarthroplasty using a "triceps-on" approach for the management of acute distal humeral fractures.

PubMed

Phadnis, Joideep; Banerjee, Samik; Watts, Adam C; Little, Nicholas; Hearnden, Anthony; Patel, Vipul R

2015-08-01

Total elbow arthroplasty is an established option for the primary treatment of acute distal humeral fractures, but there are sparse data regarding elbow hemiarthroplasty (EHA) as an alternative. We present the outcome of EHA performed with a modular anatomic prosthesis and a "triceps-on" surgical technique. Eighteen consecutive patients underwent EHA for an acute fracture. Two patients died, leaving a study group of 16 patients with minimum 2-year follow-up. Clinical evaluation included range of motion; Mayo Elbow Performance Score; Quick Disabilities of the Arm, Shoulder, and Hand score; and Oxford Elbow Score. Radiographic assessment looked at alignment, evidence of loosening, ulnar and radial head wear, heterotopic ossification, and whether healing of the condyles had occurred. Mean follow-up was 35 months (24-79 months). The mean scores were as follows: Mayo Elbow Performance Score, 89.6; shortened Disabilities of the Arm, Shoulder, and Hand score, 11.2; and Oxford Elbow Score, 43.7. The mean flexion and pronation-supination arcs were 116° and 172° respectively. Radial head wear was absent in 13 patients and mild in 3. Ulnar wear was absent in 6 patients, mild in 8, and moderate in 2. Wear was not associated with greater pain or inferior functional scores. There was no sign of aseptic loosening, and complete condylar bone union occurred in 15 elbows. There was 1 complication, a transient ulnar nerve neurapraxia that resolved without intervention. EHA with a modular anatomic implant using a triceps-on approach is a reliable technique for the management of acute unreconstructible distal humeral fractures in older patients. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Arthroscopic hip preservation surgery practice patterns: an international survey

PubMed Central

Smith, Kevin M.; Gerrie, Brayden J.; McCulloch, Patrick C.; Lewis, Brian D.; Mather, R. Chad; Van Thiel, Geoffrey; Nho, Shane J.

2017-01-01

Abstract To design and conduct a survey analyzing pre-, intra- and post- hip arthroscopy practice patterns among hip arthroscopists worldwide. A 21-question, IRB-exempt, HIPAA-compliant, cross-sectional survey was conducted via email using SurveyMonkey to examine pre-operative evaluation, intra-operative techniques and post-operative management. The survey was administered internationally to 151 hip arthroscopists identified from publicly available sources. Seventy-five respondents completed the survey (151 ± 116 hip arthroscopy procedures per year; 8.6 ± 7.1 years hip arthroscopy experience). Standing AP pelvis, false profile and Dunn 45 were the most common radiographs utilized. CT scans were utilized by 54% of surgeons at least some of the time. Only 56% of participants recommended an arthrogram with MRI. Nearly all surgeons either never (40%) or infrequently (58%) performed arthroscopy in Tönnis grade-2 or grade-3 osteoarthritis. Surgeons rarely performed hip arthroscopy on patients with dysplasia (51% never; 44% infrequently). Only 25% of participants perform a routine ‘T’ capsulotomy and 41% close the capsule if the patient is at risk for post-operative instability. Post-operatively, 52% never use a brace, 39% never use a continuous passive motion, 11% never recommended heterotopic ossification prophylaxis and 30% never recommended formal thromboembolic disease prophylaxis. Among a large number of high-volume experienced hip arthroscopists worldwide, pre-, intra- and post- hip arthroscopy practice patterns have been established and reported. Within this cohort of respondents, several areas of patient evaluation and management remain discordant and controversial without universal agreement. Future research should move beyond expert opinion level V evidence towards high-quality appropriately designed and conducted investigations. PMID:28630717

Postoperative Complications Associated With rhBMP2 Use in Posterior/Posterolateral Lumbar Fusion

PubMed Central

Esmail, Nabil; Buser, Zorica; Cohen, Jeremiah R.; Brodke, Darrel S.; Meisel, Hans-Joerg; Park, Jong-Beom; Youssef, Jim A.; Wang, Jeffrey C.; Yoon, S. Tim

2017-01-01

Study Design: Retrospective database review. Objective: Posterior/posterolateral lumbar fusion (PLF) is an effective treatment for a variety of spinal disorders; however, variations in surgical technique have different complication profiles. The aim of our study was to quantify the frequency of various complications in patients undergoing PLF with and without human recombinant bone morphogenetic protein 2 (rhBMP2). Methods: We queried the orthopedic subset of the Medicare database (PearlDiver) between 2005 and 2011 for patients undergoing PLF procedures with and without rhBMP2. Complication and reoperation rates were analyzed within 1 year of the index procedure. Complications assessed include: acute renal failure, deep vein thrombosis, dural tear, hematoma, heterotopic ossification, incision and drainage, cardiac complications, nervous system complications, osteolysis, pneumonia, pseudarthrosis, pulmonary embolism, radiculopathy, respiratory complications, sepsis, urinary retention, urinary tract infection, mechanical, and wound complications. Chi-square analysis was used to calculate the complication differences between the groups. Results: Our data revealed higher overall complication rates in patients undergoing PLF with rhBMP2 versus no_rhBMP2 (76.9% vs 68.8%, P < .05). Stratified by gender, rhBMP2 males had higher rates of mechanical complications, pseudarthrosis, and reoperations compared with no_rhBMP2 males (P < .05), whereas rhBMP2 females had higher rates of pseudarthrosis, urinary tract infection, and urinary retention compared with no_rhBMP2 females (P < .05). Conclusion: Our data revealed higher overall complication rates in PLF patients given rhBMP2 compared with no_rhBMP2. Furthermore, our data suggests that rhBMP2-associated complications may be gender specific. PMID:29662744

Correlation between cervical lordosis and adjacent segment pathology after anterior cervical spinal surgery.

PubMed

Lee, Soo Eon; Jahng, Tae-Ahn; Kim, Hyun Jib

2015-12-01

To evaluate the incidence and risk factors for adjacent segment pathology (ASP) after anterior cervical spinal surgery. Fourteen patients (12 male, mean age 47.1 years) who underwent single-level cervical disk arthroplasty (CDA group) and 28 case-matched patients (24 male, mean age 53.6 years) who underwent single-level anterior cervical discectomy and fusion (ACDF group) were included. Presence of radiologic ASP (RASP) was based on observed changes in anterior osteophytes, disks, and calcification of the anterior longitudinal ligament on lateral radiographs. The mean follow-up period was 43.4 months in the CDA group and 44.6 months in the ACDF group. At final follow-up, ASP was observed in 5 (35.7%) CDA patients and 16 (57.1%) ACDF patients (p = 0.272). The interval between surgery and ASP development was 33.8 months in the CDA group and 16.3 months in the ACDF group (p = 0.046). The ASP risk factor analysis indicated postoperative cervical angle at C3-7 being more lordotic in non-ASP patients in both groups. Restoration of lordosis occurred in the CDA group regardless of the presence of ASP, but heterotopic ossification development was associated with the presence of ASP in the CDA group. And the CDA group had significantly greater clinical improvements than those in the ACDF group when ASP was present. In both CDA and ACDF patients, RASP developed, but CDA was associated with a delay in ASP development. A good clinical outcome was expected in CDA group, even when ASP developed. Restoration of cervical lordosis was an important factor in anterior cervical spine surgery.

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

Strauss, Jonathan B.; Chen, Sea S.; Shah, Anand P.

Purpose: Heterotopic ossification (HO), or abnormal bone formation, is a common sequela of total hip arthroplasty. This abnormal bone can impair joint function and must be surgically removed to restore mobility. HO can be prevented by postoperative nonsteroidal anti-inflammatory drug (NSAID) use or radiotherapy (RT). NSAIDs are associated with multiple toxicities, including gastrointestinal bleeding. Although RT has been shown to be more efficacious than NSAIDs at preventing HO, its cost-effectiveness has been questioned. Methods and Materials: We performed an analysis of the cost of postoperative RT to the hip compared with NSAID administration, taking into account the costs of surgerymore » for HO formation, treatment-induced morbidity, and productivity loss from missed work. The costs of RT, surgical revision, and treatment of gastrointestinal bleeding were estimated using the 2007 Medicare Fee Schedule and inpatient diagnosis-related group codes. The cost of lost wages was estimated using the 2006 median salary data from the U.S. Census Bureau. Results: The cost of administering RT was estimated at $899 vs. $20 for NSAID use. After accounting for the additional costs associated with revision total hip arthroplasty and gastrointestinal bleeding, the corresponding estimated costs were $1,208 vs. $930. Conclusion: If the costs associated with treatment failure and treatment-induced morbidity are considered, the cost of NSAIDs approaches that of RT. Other NSAID morbidities and quality-of-life differences that are difficult to quantify add to the cost of NSAIDs. These considerations have led us to recommend RT as the preferred modality for use in prophylaxis against HO after total hip arthroplasty, even when the cost is considered.« less

Combined spinal epidural anesthesia in achondroplastic dwarf for femur surgery

PubMed Central

Bakhshi, Rochana Girish; Jagtap, Sheetal R.

2011-01-01

Achondroplasia is the commonest form of short-limbed dwarfism and occurs in 1:26,000-40,000 live births. This is an autosomal dominant disorder with abnormal endochondral ossification whereas periosteal and intramembranous ossification are normal. The basic abnormality is a disturbance of cartilage formation mainly at the epiphyseal growth plates and at the base of the skull. The anesthetic management of achondroplastic dwarfs is a challenge to the anesthesiologist. Both regional as well as general anesthesia have their individual risks and consequences. We report a case of an achondroplastic dwarf in whom combined spinal epidural anesthesia was used for fixation of a fractured femur. The patient had undergone previous femur surgery under general anesthesia since he had been informed that spinal anesthesia could be very problematic. There was no technical difficulty encountered during the procedure and an adequate level was achieved with low-dose local anesthetics without any problem. Postoperative pain relief was offered for three consecutive postoperative days using epidural tramadol. We discuss the anesthetic issues and highlight the role of combined spinal epidural anesthesia with low-dose local anesthetics in this patient. This approach also helped in early ambulation and postoperative pain relief. PMID:24765361

Vascular Calcification and Stone Disease: A New Look towards the Mechanism

PubMed Central

Yiu, Allen J.; Callaghan, Daniel; Sultana, Razia; Bandyopadhyay, Bidhan C.

2015-01-01

Calcium phosphate (CaP) crystals are formed in pathological calcification as well as during stone formation. Although there are several theories as to how these crystals can develop through the combined interactions of biochemical and biophysical factors, the exact mechanism of such mineralization is largely unknown. Based on the published scientific literature, we found that common factors can link the initial stages of stone formation and calcification in anatomically distal tissues and organs. For example, changes to the spatiotemporal conditions of the fluid flow in tubular structures may provide initial condition(s) for CaP crystal generation needed for stone formation. Additionally, recent evidence has provided a meaningful association between the active participation of proteins and transcription factors found in the bone forming (ossification) mechanism that are also involved in the early stages of kidney stone formation and arterial calcification. Our review will focus on three topics of discussion (physiological influences—calcium and phosphate concentration—and similarities to ossification, or bone formation) that may elucidate some commonality in the mechanisms of stone formation and calcification, and pave the way towards opening new avenues for further research. PMID:26185749

Forward Genetics Defines Xylt1 as a Key, Conserved Regulator of Early Chondrocyte Maturation and Skeletal Length

PubMed Central

Mis, Emily K.; Liem, Karel F.; Kong, Yong; Schwartz, Nancy B.; Domowicz, Miriam; Weatherbee, Scott D.

2014-01-01

The long bones of the vertebrate body are built by the initial formation of a cartilage template that is later replaced by mineralized bone. The proliferation and maturation of the skeletal precursor cells (chondrocytes) within the cartilage template and their replacement by bone is a highly coordinated process which, if misregulated, can lead to a number of defects including dwarfism and other skeletal deformities. This is exemplified by the fact that abnormal bone development is one of the most common types of human birth defects. Yet, many of the factors that initiate and regulate chondrocyte maturation are not known. We identified a recessive dwarf mouse mutant (pug) from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. pug mutant skeletal elements are patterned normally during development, but display a ~20% length reduction compared to wild-type embryos. We show that the pug mutation does not lead to changes in chondrocyte proliferation but instead promotes premature maturation and early ossification, which ultimately leads to disproportionate dwarfism. Using sequence capture and high-throughput sequencing, we identified a missense mutation in the Xylosyltransferase 1 (Xylt1) gene in pug mutants. Xylosyltransferases catalyze the initial step in glycosaminoglycan (GAG) chain addition to proteoglycan core proteins, and these modifications are essential for normal proteoglycan function. We show that the pug mutation disrupts Xylt1 activity and subcellular localization, leading to a reduction in GAG chains in pug mutants. The pug mutant serves as a novel model for mammalian dwarfism and identifies a key role for proteoglycan modification in the initiation of chondrocyte maturation. PMID:24161523

Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length.

PubMed

Mis, Emily K; Liem, Karel F; Kong, Yong; Schwartz, Nancy B; Domowicz, Miriam; Weatherbee, Scott D

2014-01-01

The long bones of the vertebrate body are built by the initial formation of a cartilage template that is later replaced by mineralized bone. The proliferation and maturation of the skeletal precursor cells (chondrocytes) within the cartilage template and their replacement by bone is a highly coordinated process which, if misregulated, can lead to a number of defects including dwarfism and other skeletal deformities. This is exemplified by the fact that abnormal bone development is one of the most common types of human birth defects. Yet, many of the factors that initiate and regulate chondrocyte maturation are not known. We identified a recessive dwarf mouse mutant (pug) from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. pug mutant skeletal elements are patterned normally during development, but display a ~20% length reduction compared to wild-type embryos. We show that the pug mutation does not lead to changes in chondrocyte proliferation but instead promotes premature maturation and early ossification, which ultimately leads to disproportionate dwarfism. Using sequence capture and high-throughput sequencing, we identified a missense mutation in the Xylosyltransferase 1 (Xylt1) gene in pug mutants. Xylosyltransferases catalyze the initial step in glycosaminoglycan (GAG) chain addition to proteoglycan core proteins, and these modifications are essential for normal proteoglycan function. We show that the pug mutation disrupts Xylt1 activity and subcellular localization, leading to a reduction in GAG chains in pug mutants. The pug mutant serves as a novel model for mammalian dwarfism and identifies a key role for proteoglycan modification in the initiation of chondrocyte maturation. © 2013 Published by Elsevier Inc.

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

Specification of posterior midbrain region in zebrafish neuroepithelium.

PubMed

Miyagawa, T; Amanuma, H; Kuroiwa, A; Takeda, H

1996-04-01

The developing vertebrate nervous system displays a pronounced anterior-posterior (A-P) pattern, but the mechanism that generates this pattern is poorly understood. We examined through cell-transplantation experiments, when and how the cells in the zebrafish posterior midbrain acquire regional specificity along the A-P axis as shown by pax[b] gene expression. Labelled donor cells from the presumptive midbrain region at various stages were transplanted into more anterior part of unlabelled host embryos of the same developmental stage, and the expression of pax[b] in the donor cells were examined by in situ hybridization. The results indicated that, in the cells from the presumptive midbrain region, expression of pax[b] was determined as early as the 55%-epiboly (6.5 h, early gastrulation) when the underlying hypoblastic layer reached the presumptive midbrain region. We also found that when transplanted heterotopically, anterior, but not posterior, hypoblast cells induced expression of pax[b] in the overlying ectoderm. Expression of a midbrain specific gene is determined during early gastrulation and the hypoblastic layer plays an important role in this determination process.

[Thoracic spinal cord compression at two levels due to ligamentum flavum calcification. Case report].

PubMed

Gondim, J; Ramos Júnior, F

1998-06-01

Calcification and/or ossification of the ligamenta flava is a well reported clinicopathologic entity causing narrowing of the spinal canal cord compression. It has been described almost exclusively in Japanese people. The authors present the case of a non Japanese patient with thoracic myelopathy caused by ossification of the ligamentum flavum.

High-density human mesenchymal stem cell rings with spatiotemporally-controlled morphogen presentation as building blocks for engineering bone diaphyseal tissue

PubMed Central

Herberg, Samuel; Varghai, Daniel; Cheng, Yuxuan; Dikina, Anna D.; Dang, Phuong N.; Rolle, Marsha W.; Alsberg, Eben

2018-01-01

Emerging biomimetic tissue engineering strategies aim to partially recapitulate fundamental events that transpire during embryonic skeletal development; namely, cellular self-organization and targeted morphogenetic pathway activation. Here, we describe self-assembled, scaffold-free human mesenchymal stem cell (hMSC) rings featuring microparticle-mediated presentation of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2). We tested the hypothesis that spatiotemporally-controlled dual presentation of TGF-β1 and BMP-2 is superior in modulating in vitro endochondral ossification of high-density cellular constructs compared to single morphogen delivery. hMSC rings were engineered by seeding cells with microparticles presenting (1) TGF-β1, (2) BMP-2, or (3) TGF-β1 + BMP-2 in custom agarose wells to facilitate self-assembly within 2 d, followed by horizontal culture on glass tubes for 5 weeks. At day 2, hMSC rings across groups revealed homogenous cellular organization mimetic of early mesenchymal condensation with no evidence of new matrix or mineral deposition. Significant early chondrogenic and osteogenic priming occurred with TGF-β1 + BMP-2 presentation compared to single morphogen-loaded groups. By week 5, TGF-β1-loaded hMSC rings had undergone chondrogenesis, while presentation of BMP-2 alone or in conjunction with TGF-β1 stimulated chondrogenesis, chondrocyte hypertrophy, and osteogenesis indicative of endochondral ossification. Importantly, tissue mineralization was most compelling with TGF-β1 + BMP-2 loading. Lastly, hMSC ring 'building blocks' were shown to efficiently fuse into tubes within 6 d post self-assembly. The resulting tubular tissue units exhibited structural integrity, highlighting the translational potential of this advanced biomimetic technology for potential early implantation in long bone defects. PMID:29577017

Pannus inflammation in sacroiliitis following immune pathological injury and radiological structural damage: a study of 193 patients with spondyloarthritis.

PubMed

Wang, Dan Min; Lin, Ling; Peng, Jian Hua; Gong, Yao; Hou, Zhi Duo; Chen, Su Biao; Xiao, Zheng Yu

2018-06-08

The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. Fine needle aspiration biopsy of the sacroiliac joint (SIJ) was performed in 193 patients with axSpA. Clinical, laboratory, and imaging data were collected at baseline and during the follow up. Immunohistochemistry analysis was performed to detect CD34+ microvessels, CD68+ osteoclasts/macrophages, vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), and caspase-3. Autopsy subjects were used as controls. In early sacroiliitis (grade 0-1) all pathological features could be observed, with the most common being subchondral pannus formation. Among the 193 patients, 98 were followed up for 1-13 years (mean 3.6 years); 63.3% had radiological progression at the endpoint. Multiple regression analysis showed that cartilage pannus invasion (OR 2.99, P = 0.010) and endochondral ossification (OR 3.97, P = 0.049) at baseline were risk factors for radiological structural damage. Compared to SIJ controls, the subchondral microvessel density, number of CD68+ multinuclear osteoclasts, and the levels of VEGF, caspase-3, MMP-3, and TNF-α expressed at the interface of the bone and cartilage were significantly higher in patients with sacroiliitis. Subchondral fibrovascular tissue formation is the most important pathological feature in early sacroiliitis. The existence of cartilage pannus invasion or endochondral ossification at baseline can predict radiological structural damage during the follow up.

Management of cerebrospinal fluid leakage after anterior decompression for ossification of posterior longitudinal ligament in the thoracic spine: the utilization of a volume-controlled pseudomeningocele.

PubMed

Cho, Ji Young; Chan, Chee Keong; Lee, Sang-Ho; Choi, Won-Chul; Maeng, Dae Hyeon; Lee, Ho-Yeon

2012-06-01

Retrospective review To determine the efficacy of management of cerebrospinal fluid (CSF) leakage after the anterior thoracic approach. CSF leakage after incidental durotomy commonly occurs after anterior thoracic ossification of posterior longitudinal ligament (OPLL) surgery. Pseudomeningocele will invariably form under such circumstances. Among them, uncontrolled CSF leakage with a fistulous condition is problematic. As a solution, we have managed these durotomies with chest drains alone without any CSF drainage by the concept of a "volume-controlled pseudomeningocele." Between 2001 and 2009, CSF leakage occurred in 26 patients (37.7%) of the total 69 patients who underwent anterior decompression for thoracic OPLL. In the initial 11 cases, subarachnoid drainage was utilized as an augmentive measure in combination with chest tube drainage in the postoperative period (group A). In the subsequent 15 cases, the durotomy was managed in a similar manner but in the absence of any subarachnoid drainage (group B). Various parameters such as the duration of postoperative hospital stay, clinical outcome score, drainage output, resolution of CSF leakage, complications, and additional surgery performed were analyzed and compared between the 2 groups. A resolution of the CSF leakage grading system was also proposed for the residual pseudomeningocele that formed in each group. There were statistically no significant differences in the outcome parameters between the 2 groups and also in patients with grade I or grade II residual pseudomeningocele of the new grading system. Two complications occurred in group A. No reexploration for persistent CSF leakage was required in both groups. CSF leakage managed with controlled chest tube drainage can produce a comparable result with those with additional subarachnoid drainage when watertight dural repair is impossible. The concept of controlled pseudomeningocele may be a useful and practical technique for the treatment of CSF leakage

The transcription factor Lc-Maf participates in Col27a1 regulation during chondrocyte maturation

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

Mayo, Jaime L.; Holden, Devin N.; Barrow, Jeffery R.

2009-08-01

The transcription factor Lc-Maf, which is a splice variant of c-Maf, is expressed in cartilage undergoing endochondral ossification and participates in the regulation of type II collagen through a cartilage-specific Col2a1 enhancer element. Type XXVII and type XI collagens are also expressed in cartilage during endochondral ossification, and so enhancer/reporter assays were used to determine whether Lc-Maf could regulate cartilage-specific enhancers from the Col27a1 and Col11a2 genes. The Col27a1 enhancer was upregulated over 4-fold by Lc-Maf, while the Col11a2 enhancer was downregulated slightly. To confirm the results of these reporter assays, rat chondrosarcoma (RCS) cells were transiently transfected with anmore » Lc-Maf expression plasmid, and quantitative RT-PCR was performed to measure the expression of endogenous Col27a1 and Col11a2 genes. Endogenous Col27a1 was upregulated 6-fold by Lc-Maf overexpression, while endogenous Col11a2 was unchanged. Finally, in situ hybridization and immunohistochemistry were performed in the radius and ulna of embryonic day 17 mouse forelimbs undergoing endochondral ossification. Results demonstrated that Lc-Maf and Col27a1 mRNAs are coexpressed in proliferating and prehypertrophic regions, as would be predicted if Lc-Maf regulates Col27a1 expression. Type XXVII collagen protein was also most abundant in prehypertrophic and proliferating chondrocytes. Others have shown that mice that are null for Lc-Maf and c-Maf have expanded hypertrophic regions with reduced ossification and delayed vascularization. Separate studies have indicated that Col27a1 may serve as a scaffold for ossification and vascularization. The work presented here suggests that Lc-Maf may affect the process of endochondral ossification by participating in the regulation of Col27a1 expression.« less

Sex-Related Differences in the Developmental Morphology of the Atlas: A Computed Tomography Study.

PubMed

Asukai, Mitsuru; Fujita, Tomotada; Suzuki, Daisuke; Nishida, Tatsuya; Ohishi, Tsuyoshi; Matsuyama, Yukihiro

2018-05-15

A retrospective study. To elucidate sex-related differences in the age at synchondroses closure, the normative size of the atlas, and the ossification patterns of the atlas in Japanese children. The atlas develops from three ossification centers during childhood. The anterior and posterior synchondroses, which are separate ossification centers, mimic fracture lines on computed tomography (CT). Sex-related differences of age dependent morphological changes of the atlas in a large sample size have not been reported. This study analyzed data of 688 subjects (449 boys) between 0 and 18 years old who underwent CT examination of the head and/or neck between January 2010 and July 2016. The age at synchondroses closure, anteroposterior outer, inner, and spinal canal widths of the atlas, and variations of the ossification centers were examined. Anterior synchondroses closed by 10 years in boys and by 7 years in girls. Significant earlier closure of anterior synchondroses was observed in girls than in boys (P < 0.05 at 4 and 5 years old). Posterior synchondrosis closed by 6 years in boys and by 5 years in girls. The outer, inner, and spinal canal widths increased up to 10 to 15 years in both sexes, although all three parameters in girls peaked 3 years earlier than those in boys. All parameters in boys were significantly larger than those in girls, except in the 10- to 12-year-old age category. Two or more ossification centers in the anterior arch were observed in 18.3% subjects, and 6% had midline ossification centers in the posterior arch of the atlas. Distinct sex-related differences in the age at anterior synchondroses closure and the size of the atlas were observed in Japanese children. Knowledge of morphological features of the atlas could help distinguish fractures from synchondroses. 3.

Intraocular osseous metaplasia. A clinico-pathological study.

PubMed

Vemuganti, Geeta K; Honavar, Santosh G; Jalali, Subhadra

2002-09-01

To evaluate the clinico-pathologic features of intraocular osseous metaplasia. Pathology specimens of enucleated eyes submitted to the ophthalmic pathology service at a tertiary eye-care referral center between January 1995 and June 1999 were studied for intraocular osseous metaplasia. Specific histopathologic features noted in specimens with osseous metaplasia were the presence of retinal detachment, gliosis, retinal pigment epithelial hyperplasia, drusen, epiretinal membrane, fibrovascular proliferation and inflammation. Immunohistochemistry using monoclonal antibody against glial fibrillary acidic protein was performed to assess the glial component within the membranes and the proliferative vitreoretinal mass. Clinical records were reviewed and correlated with histopathologic findings. Osseous metaplasiaS was noted in 8 of 151 (5.2%) eyes examined. Clinical diagnosis in these was phthisis bulbi, staphyloma, absolute glaucoma and microphthalmos. Enucleation was performed for relief of symptoms (in painful blind eyes) or for cosmesis, and in an eye inciting sympathetic ophthalmia. Retinal detachment, gliosis and retinal pigment epithelial hyperplasia were noted in all the cases. Drusen with calcification or ossification (5 of 8), fibrovascular proliferation in the vitreous (5 of 8) and active inflammation (4 of 8) were the other associated histologic features. Location of ossification was subretinal in 3 cases, preretinal (ora serrata) in 1 case and in both locations in 4 cases. The eyes with subretinal osseous metaplasia had associated calcified drusen, while preretinal ossification was seen within the fibrovascular membranes. Chronic retinal detachment, hyperplasia and transdifferentiation of retinal pigment epithelium appear to be a few of the prerequisites for intraocular osseous metaplasia. Ossification can occur at isolated subretinal and preretinal locations or can involve both. Though a larger study is required to postulate the chronology of events, in

Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

PubMed Central

Yu, Yan Yiu; Lieu, Shirley; Hu, Diane; Miclau, Theodore; Colnot, Céline

2012-01-01

Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones. PMID:22359627

Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

PubMed

Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

2018-05-01

GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

The Development of the Skull of the Egyptian Cobra Naja h. haje (Squamata: Serpentes: Elapidae)

PubMed Central

Khannoon, Eraqi R.; Evans, Susan E.

2015-01-01

Background The study of craniofacial development is important in understanding the ontogenetic processes behind morphological diversity. A complete morphological description of the embryonic skull development of the Egyptian cobra, Naja h. haje, is lacking and there has been little comparative discussion of skull development either among elapid snakes or between them and other snakes. Methodology/Principal Findings We present a description of skull development through a full sequence of developmental stages of the Egyptian cobra, and compare it to other snakes. Associated soft tissues of the head are noted where relevant. The first visible ossification centres are in the supratemporal, prearticular and surangular, with slight ossification visible in parts of the maxilla, prefrontal, and dentary. Epiotic centres of ossification are present in the supraoccipital, and the body of the supraoccipital forms from the tectum posterior not the tectum synoticum. The venom glands are visible as distinct bodies as early at stage 5 and enlarge later to extend from the otic capsule to the maxilla level with the anterior margin of the eye. The gland becomes more prominent shortly before hatching, concomitant with the development of the fangs. The tongue shows incipient forking at stage 5, and becomes fully bifid at stage 6. Conclusions/Significance We present the first detailed staging series of cranial development for the Egyptian cobra, Naja h. haje. This is one of the first studies since the classical works of G. de Beer and W. Parker that provides a detailed description of cranial development in an advanced snake species. It allows us to correct errors and misinterpretations in previous accounts which were based on a small sample of specimens of uncertain age. Our results highlight potentially significant variation in supraoccipital formation among squamates and the need for further research in this area. PMID:25860015

Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

PubMed

Menezes, Nina M; Olear, Elizabeth A; Li, Xiaoming; Connolly, Susan A; Zurakowski, David; Foley, Mary; Shapiro, Frederic; Jaramillo, Diego

2006-05-01

To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for

Congenital hypothyroidism and concurrent renal insufficiency in a kitten.

PubMed

Lim, Chee Kin; Rosa, Chantal T; de Witt, Yolanda; Schoeman, Johan P

2014-11-14

A 3-month-old male domestic short-hair kitten was presented with chronic constipation and disproportionate dwarfism. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of congenital primary hypothyroidism was confirmed by low serum total thyroxine and high thyroid stimulating hormone concentrations. Appropriate supplementation of levothyroxine was instituted. The kitten subsequently developed mild renal azotaemia and renal proteinuria, possibly as a consequence of treatment or an unmasked congenital renal developmental abnormality. Early recognition, diagnosis and treatment are vital as alleviation of clinical signs may depend on the cat's age at the time of diagnosis.

Ontogeny of the Appendicular Skeleton in Melanosuchus niger (Crocodylia: Alligatoridae).

PubMed

Vieira, Lucélia Gonçalves; Santos, André Luiz Quaqliatto; Lima, Fabiano Campos; Mendonça, Sônia Helena Santesso Teixeira de; Menezes, Lorena Tannus; Sebben, Antônio

2016-08-01

The objective of the present study was to analyze chondrogenesis and the ossification pattern of the limbs of Melanosuchus niger in order to contribute with possible discussions on homology and the fusion pattern of autopodial elements and phylogeny. In the Reserva Extrativista do Lago Cuniã, Rondônia, Brazil, six nests were marked and two eggs removed from each nest at 24-hour intervals until hatching. Embryos were cleared using KOH; bone tissue was stained with alizarin red S and cartilage with Alcian blue. Routine staining with HE was also performed. In the pectoral girdle, the scapula showed ossification centers before the coracoid process. In the pelvic girdle, the ilium and the ischium were condensed as a single cartilage, although ossification took place through two separate centers, forming distinct elements in the adult. The pubis developed from an independent cartilaginous center with free end, which reflects its function in breathing. In the initial stages, the stylopodium and the zeugopodium developed from the condensation of a Y-shaped cartilage in the limbs, and differentiation of the primary axis and digital arch were observed. The greatest changes were observed in the mesopodia. In their evolution, Crocodylia underwent a vast reduction in the number of autopodial elements as a consequence of fusions and ossification of some elements. This study shows that the chondrogenesis and ossification sequences are dissociated. Moreover, the differences between M. niger and other species show clear variation in the patterns for these events in Alligatoridae.

Primary homologies of the circumorbital bones of snakes.

PubMed

Palci, Alessandro; Caldwell, Michael W

2013-09-01

Some snakes have two circumorbital ossifications that in the current literature are usually referred to as the postorbital and supraorbital. We review the arguments that have been proposed to justify this interpretation and provide counter-arguments that reject those conjectures of primary homology based on the observation of 32 species of lizards and 81 species of snakes (both extant and fossil). We present similarity arguments, both topological and structural, for reinterpretation of the primary homologies of the dorsal and posterior orbital ossifications of snakes. Applying the test of similarity, we conclude that the posterior orbital ossification of snakes is topologically consistent as the homolog of the lacertilian jugal, and that the dorsal orbital ossification present in some snakes (e.g., pythons, Loxocemus, and Calabaria) is the homolog of the lacertilian postfrontal. We therefore propose that the terms postorbital and supraorbital should be abandoned as reference language for the circumorbital bones of snakes, and be replaced with the terms jugal and postfrontal, respectively. The primary homology claim for the snake "postorbital" fails the test of similarity, while the term "supraorbital" is an unnecessary and inaccurate application of the concept of a neomorphic ossification, for an element that passes the test of similarity as a postfrontal. This reinterpretation of the circumorbital bones of snakes is bound to have important repercussions for future phylogenetic analyses and consequently for our understanding of the origin and evolution of snakes. Copyright © 2013 Wiley Periodicals, Inc.

Can K-Line Predict the Clinical Outcome of Anterior Controllable Antedisplacement and Fusion Surgery for Cervical Myelopathy Caused by Multisegmental Ossification of the Posterior Longitudinal Ligament?

PubMed

Sun, Jing Chuan; Zhang, Bin; Shi, Jiangang; Sun, Kai Qiang; Huan, Le; Sun, Xiao Fei; Liu, Ning; Zheng, Bing; Wang, Hai Bo

2018-04-27

To analyze the correlation between the K-line-based classification of patients with ossification of the posterior longitudinal ligament (OPLL) and their outcome after anterior controllable antedisplacement and fusion (ACAF) surgery. A series of 24 patients with multisegmental OPLL were enrolled. All patients underwent ACAF surgery. First, the patients were classified into 2 groups according to their K-line classification. Then, we separated the patients into subgroups according to their OPLL thickness. The Japanese Orthopaedic Association scores before and 6 months after surgery were studied, and the recovery rate (RR) was calculated. The preoperative and postoperative radiologic parameters were also investigated. Clinical and radiographic assessments showed no significant correlation between the K-line-based classification of patients with OPLL and their outcome of ACAF surgery (P > 0.05). When the OPLL was ≤6 mm thick, K-line-based classification groups had a similar change of occupation ratio and RR (P > 0.05). However, when the OPLL was >6 mm thick, the mean RR was 61.8% ± 14.0% in the K-line (+) group and 78.3% ± 9.7% in the K-line (-) group (P < 0.05), and the mean was 16.0% ± 4.2% in the K-line (+) group and 28.0% ± 7.1% in the K-line (-) group (P < 0.05). This study shows that K-line can predict the clinical outcome of ACAF surgery for multisegmental OPLL in a different way from posterior decompression surgery. When the OPLL was thin, the outcome was satisfactory and there was no correlation with K-line-based classification of patients with OPLL. When the OPLL was >6 mm thick, the K-line (-) group patients had a better outcome than did K-line (+) group patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification and characterization of regulatory elements in the promoter of ACVR1, the gene mutated in Fibrodysplasia Ossificans Progressiva

PubMed Central

2013-01-01

Background The ACVR1 gene encodes a type I receptor for bone morphogenetic proteins (BMPs). Mutations in the ACVR1 gene are associated with Fibrodysplasia Ossificans Progressiva (FOP), a rare and extremely disabling disorder characterized by congenital malformation of the great toes and progressive heterotopic endochondral ossification in muscles and other non-skeletal tissues. Several aspects of FOP pathophysiology are still poorly understood, including mechanisms regulating ACVR1 expression. This work aimed to identify regulatory elements that control ACVR1 gene transcription. Methods and results We first characterized the structure and composition of human ACVR1 gene transcripts by identifying the transcription start site, and then characterized a 2.9 kb upstream region. This region showed strong activating activity when tested by reporter gene assays in transfected cells. We identified specific elements within the 2.9 kb region that are important for transcription factor binding using deletion constructs, co-transfection experiments with plasmids expressing selected transcription factors, site-directed mutagenesis of consensus binding-site sequences, and by protein/DNA binding assays. We also characterized a GC-rich minimal promoter region containing binding sites for the Sp1 transcription factor. Conclusions Our results showed that several transcription factors such as Egr-1, Egr-2, ZBTB7A/LRF, and Hey1, regulate the ACVR1 promoter by binding to the -762/-308 region, which is essential to confer maximal transcriptional activity. The Sp1 transcription factor acts at the most proximal promoter segment upstream of the transcription start site. We observed significant differences in different cell types suggesting tissue specificity of transcriptional regulation. These findings provide novel insights into the molecular mechanisms that regulate expression of the ACVR1 gene and that could be targets of new strategies for future therapeutic treatments. PMID:24047559

Risk factors for decreased range of motion and poor outcomes in open periarticular elbow fractures.

PubMed

Dickens, Jonathan F; Wilson, Kevin W; Tintle, Scott M; Heckert, Reed; Gordon, Wade T; D'Alleyrand, Jean-Claude G; Potter, Benjamin K

2015-04-01

The purpose of this study was to identify risk factors present at the time of injury that predict poor functional outcomes and heterotopic ossification (HO) in open periarticular elbow fractures. We performed a retrospective review of 136 combat-related open elbow fractures from 2003 to 2010. Patient demographics, injury characteristics, treatment variables, and complications were recorded. Functional outcomes were analyzed to determine range of motion (ROM) and Mayo Elbow Performance Score (MEPS). Secondary outcome measures included the development of HO, return to duty, and revision operation. At a median 2.7 years from injury the median MEPS was 67.8 (range 30-100) with an average ulnohumeral arc motion of 89°. Bipolar fractures, with periarticular fractures on both sides of the elbow and at least one side containing intra-articular extension, were independently associated with decreased ulnohumeral motion (p=0.02) and decreased MEPS (p<0.004). Additional independent risk factors for decreased ROM included more severe osseous comminution (p=0.001), and increased time to definitive fixation (p=0.03) and HO (p=0.02). More severe soft tissue injury (Gustilo and Anderson fracture type, p=0.02), peripheral nerve injury (p=0.04), and HO (p=0.03) were independently associated with decreased MEPS. HO developed in 65% (89/136) of extremities and was associated with more severe Orthopaedic Trauma Association (OTA) fracture type (p=0.01) and escalating Gustilo and Anderson fracture classification (p=0.049). In the largest series of open elbow fractures, we identified risk factors that portend a poor clinical outcome and decreased ROM. Bipolar elbow fractures, which have not previously been associated with worse results, are particularly prone to decreased ROM and worse outcomes. Prognostic level IV. Published by Elsevier Ltd.

[Results and experiences of conversion of hip arthrodesis ].

PubMed

Schuh, A; Zeiler, G; Werber, S

2005-03-01

With the predictably good outcome of total hip arthroplasty today (THA), hip arthrodesis currently has limited indications. Over the long term, however, most patients develop secondary degenerative arthritis in the spine, contralateral hip, and ipsilateral knee due to overloading. The deteriorating condition of these joints eventually causes the onset of pain, which often requires conversion of a fused hip to a THA. The results and experiences of conversions of a hip arthrodesis into a THA are reported. Between 1 January 1985 and 31 December 2001 conversion of a previously performed arthrodesis of the hip to THA was carried out in a total of 45 patients; 34 patients could be followed up after the conversion to THA after a mean of 77.5 months (min.: 24, max.: 208). The primary indications for the conversion were low back pain (n=21) and ipsilateral knee pain (n=13). The mean age at the time of THA was 75.3 years (min.: 32, max.: 74). The mean time interval between the arthrodesis and the conversion to THA was 30.4 years (min.: 5, max.: 66). Of 34 hips, 29 (85%) were either pain free or had minimal pain. Complications included one persisting sciatic nerve palsy, two superficial infections, two periprosthetic fractures, and two heterotopic ossifications IV degrees with one recurrence of ankylosis and one marked reduction of motion. Revision arthroplasty was performed in four hips. Postoperatively 7 patients showed no limping, 11 showed a slight limp, and 17 a pronounced limp. Recurrent dislocations occurred in one patient. We conclude that this operation can lead to satisfactory results even after a long duration of the arthrodesis. There is a high rate of complications after conversion of a hip arthrodesis to a total hip arthroplasty. These issues must be carefully considered and discussed with the patient before any conversion procedure.

Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

PubMed Central

Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

2015-01-01

Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

Success of nonoperative management of adductor longus tendon ruptures in National Football League athletes.

PubMed

Schlegel, Theodore F; Bushnell, Brandon D; Godfrey, Jenna; Boublik, Martin

2009-07-01

Acute complete ruptures of the proximal adductor longus tendon are rare but challenging injuries to treat. The limited literature supports operative treatment, but data from management of chronic groin pain in athletes indicate that anatomical attachment of the tendon to the pubis may not be required for high-level function. Nonoperative management of complete adductor rupture can provide equal results to surgical repair in terms of return to play in the National Football League. Case series; Level of evidence, 4. Using the National Football League Injury Surveillance System, adductor tendon ruptures documented by magnetic resonance imaging were identified in 19 National Football League players from 1992 to 2004. The team physician for each respective player completed a survey with information about history, physical examination, magnetic resonance imaging findings, treatment, and outcomes. Statistics were analyzed with a Student unpaired t test. Fourteen players were treated nonoperatively, and 5 players were treated with surgical repair using suture anchors. In both groups, all players eventually returned to play in the National Football League. Mean time for return to play was 6.1 +/- 3.1 weeks (range, 3-12 weeks) for the nonoperative group and 12.0 +/- 2.5 weeks (range, 10-16 weeks) for the operative group (P = .001). One player in the operative group suffered the complication of a draining wound and heterotopic ossification. Players represented a variety of positions, and 12 of 19 (63%) had experienced prior symptoms or events. Nonoperative treatment of proximal adductor tendon rupture results in a statistically significantly faster return to play than does operative treatment in athletes competing in the National Football League and avoids the risks associated with surgery while providing an equal likelihood of return to play at the professional level.

Revision of cemented hip arthroplasty using a hydroxyapatite-ceramic-coated femoral component.

PubMed

Raman, R; Kamath, R P; Parikh, A; Angus, P D

2005-08-01

We report the clinical and radiological outcome of 86 revisions of cemented hip arthroplasties using JRI-Furlong hydroxyapatite-ceramic-coated acetabular and femoral components. The acetabular component was revised in 62 hips and the femoral component in all hips. The mean follow-up was 12.6 years and no patient was lost to follow-up. The mean age of the patients was 71.2 years. The mean Harris hip and Oxford scores were 82 (59 to 96) and 23.4 (14 to 40), respectively. The mean Charnley modification of the Merle d'Aubigné and Postel score was 5 (3 to 6) for pain, 4.9 (3 to 6) for movement and 4.4 (3 to 6) for mobility. Migration of the acetabular component was seen in two hips and the mean acetabular inclination was 42.6 degrees. The mean linear polyethylene wear was 0.05 mm/year. The mean subsidence of the femoral component was 1.9 mm and stress shielding was seen in 23 (28%) with bony ingrowth in 76 (94%). Heterotopic ossification was seen in 12 hips (15%). There were three re-revisions, two for deep sepsis and one for recurrent dislocation and there were no re-revisions for aseptic loosening. The mean EuroQol EQ-5D description scores and health thermometer scores were 0.69 (0.51 to 0.89) and 79 (54 to 95), respectively. With an end-point of definite or probable loosening, the probability of survival at 12 years was 93.9% and 95.6% for the acetabular and femoral components, respectively. Overall survival at 12 years, with removal or further revision of either component for any reason as the end-point, was 92.3%. Our study supports the continued use of this arthroplasty and documents the durability of hydroxyapatite-ceramic-coated components.

Revision of failed shoulder hemiarthroplasty to reverse total arthroplasty: analysis of 157 revision implants.

PubMed

Merolla, Giovanni; Wagner, Eric; Sperling, John W; Paladini, Paolo; Fabbri, Elisabetta; Porcellini, Giuseppe

2018-01-01

There remains a paucity of studies examining the conversion of failed hemiarthroplasty (HA) to reverse total shoulder arthroplasty (RTSA). Therefore, the purpose of this study was to examine a large series of revision HA to RTSA. A population of 157 patients who underwent conversion of a failed HA to a revision RTSA from 2006 through 2014 were included. The mean follow-up was 49 months (range, 24-121 months). The indications for revision surgery included instability with rotator cuff insufficiency (n = 127) and glenoid wear (n = 30); instability and glenoid wear were associated in 38 cases. Eight patients with infection underwent 2-stage reimplantation. Patients experienced significant improvements in their preoperative to postoperative pain and shoulder range of motion (P < .0001), with median American Shoulder and Elbow Surgeons and Simple Shoulder Test scores of 60 and 6 points, respectively. There were 11 (7%) repeated revision surgeries, secondary to glenoid component loosening (n = 3), instability (n = 3), humeral component disassembly (n = 2), humeral stem loosening (n = 1), and infection (n = 2). Implant survivorship was 95.5% at 2 years and 93.3% at 5 years. There were 4 reoperations including axillary nerve neurolysis (n = 2), heterotopic ossification removal (n = 1), and hardware removal for rupture of the metal cerclage for an acromial fracture (n = 1). At final follow-up, there were 5 "at-risk" glenoid components. Patients experience satisfactory pain relief and recovery of reasonable shoulder function after revision RTSA from a failed HA. There was a relatively low revision rate, with glenoid loosening and instability being the most common causes. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Inconsistency in the Reporting of Adverse Events in Total Ankle Arthroplasty: A Systematic Review of the Literature.

PubMed

Mercer, Jeff; Penner, Murray; Wing, Kevin; Younger, Alastair S E

2016-02-01

Systems for classifying complications have been proposed for many surgical subspecialties. The goal of this systematic review was to analyze the number and frequency of different terms used to identify complications in total ankle arthroplasty. We hypothesized that this terminology would be highly variable, supporting a need for a standardized system of reporting. Studies that met predefined inclusion/exclusion criteria were analyzed to identify terminology used to describe adverse events. All terms were then tabulated and quantified with regard to diversity and frequency of use across all included studies. Terms were also grouped into 10 categories, and the number of reported occurrences of each adverse event was calculated. A reporting tool was then developed. Of 572 unique terms used to describe adverse outcomes in 117 studies, 55.9% (320/572) were used in only a single study. The category that was most frequently reported was revision surgery, with 86% of papers reporting on this event using 115 different terms. Other categories included "additional non-revision surgeries" (74% of papers, 93 terms), "loosening/osteolysis" (63% of papers, 86 terms), "fractures" (60% of papers, 53 terms), "wound problems" (52% of papers, 27 terms), "infection" (52% of papers, 27 terms), "implant problems" (50% of papers, 57 terms), "soft tissue injuries" (31% of papers, 30 terms), "heterotopic ossification" (22% of papers, 17 terms), and "pain" (18% of papers, 11 terms). The reporting of complications and adverse outcomes for total ankle arthroplasty was highly variable. This lack of consistency impedes the accurate reporting and interpretation of data required for the development of cohesive, evidence-based treatment guidelines for end-stage ankle arthritis. Standardized reporting tools are urgently needed. This study presents a prototype worksheet for the standardized assessment and reporting of adverse events. Level-III, decision analyses, systematic review of Level III

Anatomic ligament consolidation of the superior acromioclavicular ligament and the coracoclavicular ligament complex after acute arthroscopically assisted double coracoclavicular bundle stabilization.

PubMed

Jobmann, S; Buckup, J; Colcuc, C; Roessler, P P; Zimmermann, E; Schüttler, K F; Hoffmann, R; Welsch, F; Stein, T

2017-09-18

The consolidation of the acromioclavicular (AC) and coracoclavicular (CC) ligament complex after arthroscopically assisted stabilization of acute acromioclavicular joint (ACJ) separation is still under consideration. Fifty-five consecutive patients after arthroscopically assisted double-CC-bundle stabilization within 14 days after acute high-grade ACJ separation were studied prospectively. All patients were clinically analysed preoperatively (FU0) and post-operatively (FU1 = 6 months; FU2 = 12 months). The structural MRI assessments were performed at FU0 (injured ACJ) and at FU2 bilateral (radiologic control group) and assessed separately the ligament thickness and length at defined regions for the conoid, trapezoid and the superior AC ligament. Thirty-seven patients were assessed after 6.5 months and after 16.0 months. The 16-month MRI analysis revealed for all patients continuous ligament healing for the CC-complex and the superior AC ligament with in the average hypertrophic consolidation compared to the control side. Separate conoid and trapezoid strands (double-strand configuration) were detected in 27 of 37 (73%) patients, and a single-strand configuration was detected in 10 of 37 (27%) patients; both configurations showed similar CCD data. The ligament healing was not influenced by the point of surgery, age at surgery and heterotopic ossification. The clinical outcome was increased (FU0-FU2): Rowe, 47.7-97.0 pts.; TAFT, 3.9-10.6 pts.; NAS pain , 8.9-1.4 pts. (all P < 0.05). The arthroscopically assisted double-CC-bundle stabilization within 14 days after acute high-grade ACJ separation showed 16 months after surgery sufficient consolidations of the AC and double-CC ligament complex in 73%. III, Case series.

[Modified osteotomy of olecranon for the management of inter-condylar fracture of the humerus].

PubMed

Mei, Zheng-Feng; Lei, Wen-Tao; Huang, Dong-Hui; Zhao, Qi-Hui; Qu, Hang-Bo; Ni, Lian-Zhi

2017-01-25

To explore the surgical method and clinical outcome of modified osteotomy of olecranon for the treatment of inter-condylar fracture of humerus. From May 2007 to December 2012, 32 patients of intercondylar fracture of humerus were treated surgically through the approach of modified osteotomy of olecranon. The patients were 21 males and 11 females with a mean age of 46.3 years (ranged 18 to 65 years). Nineteen fractures occurred on the right extremity and 13 on the left extremity. According to the AO classification, type C1 fracture was found in 7, C2 in 11 and C3 in 14. Five patients suffered from open fracture (Gustilo type Iin 3, type II in 2). Other fractures occurred in 6 patients and the primary injury of nerve occurred 6. The healing of the osteotomy was evaluated with physical examination and plain X-ray film, and the function of elbow was assessed according to Cassebaum scale. All the patients were followed from 9 months to 5 years(average, 1.9 years). All the osteotomies healed at 7.4 weeks averagely after operation, and no nonunion, delayed union, fracture of ulna olecranon were found. Two cases had little pain on the elbow, heterotopic ossification occurred in 2 cases and cutting bone block loosed in 1 case. The function of the elbow showed excellent in 19 cases, good in 8, fair in 4 and poor in 1. The use of the approach of modified olecranon osteotomy for surgical management of intercondylar fracture of humerus has some advantages, it provides satisfactory stability with simple technical procedures avoiding inter-articular invasion, and it facilitates rehabilitation exercises and providing good results with low complication rates.

Radial Head Prosthesis Removal: a Retrospective Case Series of 14 Patients

PubMed Central

Neuhaus, Valentin; Christoforou, Dimitrios C.; Kachooei, Amir Reza; Jupiter, Jesse B.; Ring, David C.; Mudgal, Chaitanya S.

2015-01-01

Background: The purpose of this study was to report the preoperative complaints and postoperative outcome of patients after removal of the radial head prosthesis. Methods: This is a retrospective review of 14 adult patients (6 females and 8 males) from 2007 to 2011, who underwent radial head prosthesis removal by three surgeons. The average time between implantation and removal was 23 months (range from 2 weeks to 12 years, median 12 months). Results: The leading reported complaints before removal were restricted mobility of the elbow (active range of motion of less than 100 degrees) in 6, pain in 3, and pain together with restricted mobility in 4 patients. The objective findings before removal were restricted mobility of the elbow in 10 (71%), capitellar cartilage wear, loose implants, and heterotopic ossification each in 8 (57%), subluxation of the radio-capitellar joint or malpositioning of the stem in 5 (36%), and chronic infection in 2 (14%) patients. All patients with pain had wear of the capitellar cartilage on radiographs. The ulnar nerve was decompressed in four patients at the time of removal. Four patients underwent a subsequent operation for postoperative ulnar nerve symptoms 5 to 21 months after removal. Four patients were still complaining about persistent pain at the last follow-up visit. Except two patients, the total range of motion improved with a mean of 34 degrees (range 5 to 70) after a mean follow-up of 11 months. Conclusions: Removal of radial head prosthesis improved function and lessened pain in our case series. The reoperation rate was yet nearly 30% due to ulnar neuritis. Selective ulnar nerve decompression at the time of removal must be evaluated, especially in patients with expected large gain in range of motion after removal. PMID:26110173

Optimal Treatment of Malignant Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing

DTIC Science & Technology

2014-10-01

Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing 5a. CONTRACT NUMBER...in the fifth quarter of the award. 15. SUBJECT TERMS Fracture healing , bone healing , endochondral ossification, intramembranous ossification...of radiation on the two pathways of bone healing and propose an optimal method of surgical fracture repair for managing malignant osteoporotic

Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes.

PubMed

Bahney, Chelsea S; Jacobs, Linsey; Tamai, Robert; Hu, Diane; Luan, Tammy F; Wang, Miqi; Reddy, Sanjay; Park, Michelle; Limburg, Sonja; Kim, Hubert T; Marcucio, Ralph; Kuo, Alfred C

2016-03-01

Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not

Genome Wide assessment of Early Osseointegration in Implant-Adherent Cells

NASA Astrophysics Data System (ADS)

Thalji, Ghadeer N.

Objectives: To determine the molecular processes involved in osseointegration. Materials and methods: A structured literature review concerning in vitro and in vivo molecular assessment of osseointegration was performed. A rat and a human model were then used to identify the early molecular processes involved in osseointegration associated with a micro roughened and nanosurface superimposed featured implants. In the rat model, 32 titanium implants with surface topographies exhibiting a micro roughened (AT-II) and nanosurface superimposed featured implants (AT-I) were placed in the tibiae of 8 rats and subsequently harvested at 2 and 4 days after placement. Whereas in the human model, four titanium mini-implants with either a moderately roughened surface (TiOblast) or super-imposed nanoscale topography (Osseospeed) were placed in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole genome microarray using the Affymetrix 1.1 ST Array platform was used to describe the gene expression profiles that were differentially regulated by the implant surfaces. Results: The literature review provided evidence that particular topographic cues can be specifically integrated among the many extracellular signals received by the cell in its signal transduction network. In the rat model, functionally relevant categories related to ossification, skeletal system development, osteoblast differentiation, bone development and biomineral tissue development were upregulated and more prominent at AT-I compared to AT-II. In the human model, there were no significant differences when comparing the two-implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix, collagen fibril organization and

Acute quadriplegia following closed traction reduction of a cervical facet dislocation in the setting of ossification of the posterior longitudinal ligament: case report.

PubMed

Wimberley, David W; Vaccaro, Alexander R; Goyal, Nitin; Harrop, James S; Anderson, D Greg; Albert, Todd J; Hilibrand, Alan S

2005-08-01

A case report of acute quadriplegia resulting from closed traction reduction of traumatic bilateral cervical facet dislocation in a 54-year-old male with concomitant ossification of the posterior longitudinal ligament (OPLL). To report an unusual presentation of a spinal cord injury, examine the approach to reversal of the injury, and review the treatment and management controversies of acute cervical facet dislocations in specific patient subgroups. The treatment of acute cervical facet dislocations is an area of ongoing controversy, especially regarding the question of the necessity of advanced imaging studies before closed traction reduction of the dislocated cervical spine. The safety of an immediate closed, traction reduction of the cervical spine in awake, alert, cooperative, and appropriately select patients has been reported in several studies. To date, there have been no permanent neurologic deficits resulting from awake, closed reduction reported in the literature. A case of temporary, acute quadriplegia with complete neurologic recovery following successful closed traction reduction of a bilateral cervical facet dislocation in the setting of OPLL is presented. The clinical neurologic examination, radiographic, and advanced imaging studies before and after closed, traction reduction of a cervical facet dislocation are evaluated and discussed. A review of the literature regarding the treatment of acute cervical facet dislocations is presented. Radiographs showed approximately 50% subluxation of the fifth on the sixth cervical vertebrae, along with computerized tomography revealing extensive discontinuous OPLL. The cervical facet dislocation was successfully reduced with an awake, closed traction reduction, before magnetic resonance imaging (MRI) evaluation. The patient subsequently had acute quadriplegia develop, with the ensuing MRI study illustrating severe spinal stenosis at the C5, C6 level as a result of OPLL or a large extruded disc herniation

Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification.

PubMed

Hojo, Hironori; Ohba, Shinsuke; Yano, Fumiko; Saito, Taku; Ikeda, Toshiyuki; Nakajima, Keiji; Komiyama, Yuske; Nakagata, Naomi; Suzuki, Kentaro; Takato, Tsuyoshi; Kawaguchi, Hiroshi; Chung, Ung-il

2012-05-18

With regard to Hedgehog signaling in mammalian development, the majority of research has focused on Gli2 and Gli3 rather than Gli1. This is because Gli1(-/-) mice do not show any gross abnormalities in adulthood, and no detailed analyses of fetal Gli1(-/-) mice are available. In this study, we investigated the physiological role of Gli1 in osteogenesis. Histological analyses revealed that bone formation was impaired in Gli1(-/-) fetuses compared with WT fetuses. Gli1(-/-) perichondrial cells expressed neither runt-related transcription factor 2 (Runx2) nor osterix, master regulators of osteogenesis, in contrast to WT cells. In vitro analyses showed that overexpression of Gli1 up-regulated early osteogenesis-related genes in both WT and Runx2(-/-) perichondrial cells, and Gli1 activated transcription of those genes via its association with their 5'-regulatory regions, underlying the function of Gli1 in the perichondrium. Moreover, Gli1(-/-);Gli2(-/-) mice showed more severe phenotypes of impaired bone formation than either Gli1(-/-) or Gli2(-/-) mice, and osteoblast differentiation was impaired in Gli1(-/-);Gli3(-/-) perichondrial cells compared with Gli3(-/-) cells in vitro. These data suggest that Gli1 itself can induce early osteoblast differentiation, at least to some extent, in a Runx2-independent manner. It also plays a redundant role with Gli2 and is involved in the repressor function of Gli3 in osteogenesis. On the basis of these findings, we propose that upon Hedgehog input, Gli1 functions collectively with Gli2 and Gli3 in osteogenesis.

Increased FGF8 signaling promotes chondrogenic rather than osteogenic development in the embryonic skull.

PubMed

Schmidt, Linnea; Taiyab, Aftab; Melvin, Vida Senkus; Jones, Kenneth L; Williams, Trevor

2018-05-10

The bones of the cranial vault are formed directly from mesenchymal cells through intramembranous ossification rather than via a cartilage intermediate. Formation and growth of the skull bones involves the interaction of multiple cell:cell signaling pathways, with Fibroblast Growth Factors (FGFs) and their receptors exerting prominent influence. Mutations within this pathway are the most frequent cause of craniosynostosis, which is a common human craniofacial developmental abnormality characterized by the premature fusion of the cranial sutures. Here, we have developed new mouse models to investigate how different levels of increased Fgf signaling can impact the formation of the calvarial bones and associated sutures. While moderate Fgf8 overexpression resulted in delayed ossification followed by craniosynostosis of the coronal suture, higher Fgf8 levels promoted a loss of ossification and favored cartilage over bone formation across the skull. In contrast, endochondral bones were still able to form and ossify in the presence of increased Fgf8 , though the growth and mineralization of these bones were impacted to varying extents. Expression analysis demonstrated that abnormal skull chondrogenesis was accompanied by changes in genes required for Wnt signaling. Moreover, further analysis indicated that the pathology was associated with decreased Wnt signaling since the reduction in ossification could be partially rescued by halving Axin2 gene dosage. Taken together, these findings indicate that mesenchymal cells of the skull are not fated to form bone but can be forced into a chondrogenic fate via manipulation of FGF8 signaling. These results have implications for evolution of the different methods of ossification as well as for therapeutic intervention in craniosynostosis. © 2018. Published by The Company of Biologists Ltd.

Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair

PubMed Central

Hinton, R.J.; Jing, Y.; Jing, J.; Feng, J.Q.

2016-01-01

The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived). PMID:27664203

Histomorphometric Parameters of the Growth Plate and Trabecular Bone in Wild-Type and Trefoil Factor Family 3 (Tff3)-Deficient Mice Analyzed by Free and Open-Source Image Processing Software.

PubMed

Bijelić, Nikola; Belovari, Tatjana; Stolnik, Dunja; Lovrić, Ivana; Baus Lončar, Mirela

2017-08-01

Trefoil factor family 3 (Tff3) peptide is present during intrauterine endochondral ossification in mice, and its deficiency affects cancellous bone quality in secondary ossification centers of mouse tibiae. The aim of this study was to quantitatively analyze parameters describing the growth plate and primary ossification centers in tibiae of 1-month-old wild-type and Tff3 knock-out mice (n=5 per genotype) by using free and open-source software. Digital photographs of the growth plates and trabecular bone were processed by open-source computer programs GIMP and FIJI. Histomorphometric parameters were calculated using measurements made with FIJI. Tff3 knock-out mice had significantly smaller trabecular number and significantly larger trabecular separation. Trabecular bone volume, trabecular bone surface, and trabecular thickness showed no significant difference between the two groups. Although such histomorphological differences were found in the cancellous bone structure, no significant differences were found in the epiphyseal plate histomorphology. Tff3 peptide probably has an effect on the formation and quality of the cancellous bone in the primary ossification centers, but not through disrupting the epiphyseal plate morphology. This work emphasizes the benefits of using free and open-source programs for morphological studies in life sciences.

Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization.

PubMed

Holm, Erik; Aubin, Jane E; Hunter, Graeme K; Beier, Frank; Goldberg, Harvey A

2015-02-01

Bone sialoprotein (BSP) is an anionic phosphoprotein in the extracellular matrix of mineralized tissues, and a promoter of biomineralization and osteoblast development. Previous studies on the Bsp-deficient mouse (Bsp(-/-)) have demonstrated a significant bone and periodontal tissue phenotype in adulthood. However, the role of BSP during early long bone development is not known. To address this, early endochondral ossification in the Bsp(-/-) mouse was studied. Embryonic day 15.5 (E15.5) wild-type (WT) tibiae showed early stages of ossification that were absent in Bsp(-/-) mice. At E16.5, mineralization had commenced in the Bsp(-/-) mice, but staining for mineral was less intense and more dispersed compared with that in WT controls. Tibiae from Bsp(-/-) mice also demonstrated decreased mineralization and shortened length at postnatal day 0.5 (P0.5) compared to WT bones. There was no detectable difference in the number of tartrate-resistant acid phosphatase-positive foci at P0.5, although the P0.5 Bsp(-/-) tibiae had decreased Vegfα expression compared with WT tissue. Due to the shortened tibiae the growth plates were examined and determined to be of normal overall length. However, the length of the resting zone was increased in P0.5 Bsp(-/-) tibiae whereas that of the proliferative zone was decreased, with no change in the hypertrophic zone length of Bsp(-/-) mice. A reduction in cells positive for Ki-67, an S-phase cell-cycle marker, was noted in the proliferative zone. Decreased numbers of TUNEL-positive hypertrophic chondrocytes were also apparent in the Bsp(-/-) tibial growth plates, suggesting decreased apoptosis. Expression of the osteogenic markers Alp1, Col1a1, Sp7, Runx2, and Bglap was reduced in the endochondral bone of the neonatal Bsp(-/-) compared to WT tibiae. These results suggest that BSP is an important and multifaceted protein that regulates both chondrocyte proliferation and apoptosis as well as transition from cartilage to bone during

Prenatal diagnosis of boomerang dysplasia.

PubMed

Wessels, Marja W; Den Hollander, Nicolette S; De Krijger, Ronald R; Bonifé, Luisa; Superti-Furga, Andrea; Nikkels, Peter G; Willems, Patrick J

2003-10-01

Boomerang dysplasia, atelosteogenesis type 1 and Piepkorn dysplasia are bone dysplasias with an overlapping clinical spectrum characterized by deficient formation and ossification of specific elements of the skeleton. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang-like aspect of the long tubular bones. We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound. Copyright 2003 Wiley-Liss, Inc.

Harem Education and Heterotopic Imagination

ERIC Educational Resources Information Center

Aksit, Elif Ekin

2011-01-01

Education can cease to be a showcase for political projects and start serving women's lives only when the agency of women in their own education is acknowledged. In this paper I have addressed issues concerning harem education to emphasise that possible solutions to issues of girls' education require an awareness concerning the history of girls'…