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Sample records for 2-induced heterotopic ossification

  1. Preventative Therapeutics for Heterotopic Ossification

    DTIC Science & Technology

    2015-10-01

    SUMMARY Heterotopic Ossification (HO) is a pernicious, complex, debilitating and difficult to treat musculoskeletal pathology that affects a large number...callus, histomorphometry and pathology that need to be consistent and accurate from specimen to specimen. Dr. Sinha has honed her surgical procedures...Progressiva”. Musculoskeletal and Engineering Gordon Conference, Andover, NH, August 2014 (4) “Pharmacological prevention of heterotopic ossification

  2. Preventative Therapeutics for Heterotopic Ossification

    DTIC Science & Technology

    2016-12-01

    Orthop Relat Res. 2014;472:396–404. 12. Forsberg JA, Pepek JM, Wagner S, Wilson K, Flint J, Andersen RC, Tadaki D, Gage FA, Stojadinovic A, Elster EA...collections, and technical expertise; Dr Matthew Wagner for his statistical analysis; and LTC Cary L. Hannold for his detailed histological review of... Wagner S, Wilson K, Flint J, Andersen RC, Tadaki D, Gage FA, Stojadinovic A, Elster EA. Heterotopic ossification in high-energy wartime extremity

  3. Heterotopic ossification after hip arthroscopy.

    PubMed

    Amar, Eyal; Sharfman, Zachary T; Rath, Ehud

    2015-12-01

    Heterotopic ossification (HO) after hip arthroscopy is the abnormal formation of mature lamellar bone within extra skeletal soft tissues. HO may lead to pain, impaired range of motion and possibly revision surgery. There has been a substantial amount of recent research on the pathophysiology, prophylaxis and treatment of HO associated with open and arthroscopic hip surgery. This article reviews the literature on the aforementioned topics with a focus on their application in hip arthroscopy.

  4. Heterotopic ossification in wartime wounds.

    PubMed

    Forsberg, Jonathan Agner; Potter, Benjamin Kyle

    2010-01-01

    Heterotopic ossification (HO) refers to the formation of mature lamellar bone in nonosseous tissue. In the setting of high-energy wartime extremity wounds, HO is expected to complicate up to 64% of patients, has a predilection for the residual limbs of amputees, and remains a significant source of disability. Although the inciting events and the definitive cell(s) of origin continue to remain elusive, animal models and human histology samples suggest that HO formation follows a predictable sequence of events culminating in endochondral ossification. Primary prophylaxis is not medically or logistically practical in most cases because patients have generally sustained massive wounds and are undergoing serial debridements during an intercontinental aeromedical evacuation. Surgical excision of symptomatic lesions is warranted only after an appropriate trial of conservative measures and is associated with low recurrence rates in appropriately selected patients. Future research regarding prognostication and defining the early molecular biology of ectopic bone may permit individualized prophylaxis and development of novel targeted therapies.

  5. Heterotopic ossification of the quadratus lumborum muscle.

    PubMed

    Alport, Brie; Horne, David; Burbridge, Brent

    2014-01-01

    Heterotopic ossification is a benign process of mature laminar bone formation in the soft tissues. A synonymous term used to describe this pathology in muscle is myositis ossificans. The pathogenesis is unclear, but is likely multifactorial. The basic pathology is thought to be ectopic production of osseous tissue as part of a repair process in response to tissue injury. This report describes a case of heterotopic ossification of the quadratus lumborum muscle as an incidental finding. This case highlights that treatment is based on symptoms and conservative management might be appropriate for the asymptomatic patient.

  6. Heterotopic ossification after central nervous system trauma

    PubMed Central

    Sullivan, M. P.; Torres, S. J.; Mehta, S.; Ahn, J.

    2013-01-01

    Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones. PMID:23610702

  7. Heterotopic Ossification Following Combat-Related Trauma

    DTIC Science & Technology

    2010-01-01

    must account for the local anatomy , the location and severity of the heterotopic ossification, and the patient’s prior wounds and incisions. We...normal anatomy , placing critical neurovascular structures and muscle groups at risk for inadvertent injury. In some instances, major nerves and...presence of osteoprogenitors that pathologically are induced by an im- balance of local and/or systemic factors in soft tissue following traumatic

  8. Prevention and Treatment of Heterotopic Ossification

    DTIC Science & Technology

    2012-02-01

    the transport of circulating cells across the vessel to targeted sites We have characterized the expression of these genes within the tissues...demonstrating the presence of bone marrow derived or circulating stem cells, for cartilage and bone, and that these cells can be effectively blocked using... circulating stem cells, and contribution to heterotopic ossification, we presently have a series of mice which have been repopulated with HSCs (ckit

  9. Molecular and cellular mechanisms of heterotopic ossification.

    PubMed

    Ramirez, Diana M; Ramirez, Melissa R; Reginato, Anthony M; Medici, Damian

    2014-10-01

    Heterotopic ossification (HO) is a debilitating condition in which cartilage and bone forms in soft tissues such as muscle, tendon, and ligament causing immobility. This process is induced by inflammation associated with traumatic injury. In an extremely rare genetic disorder called fibrodysplasia ossificans progessiva (FOP), a combination of inflammation associated with minor soft tissue injuries and a hereditary genetic mutation causes massive HO that progressively worsens throughout the patients' lifetime leading to the formation of an ectopic skeleton. An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT). In this review, we discuss the recent evidence and mechanistic data that describe the cellular and molecular mechanisms that give rise to heterotopic bone.

  10. Molecular and cellular mechanisms of heterotopic ossification

    PubMed Central

    Ramirez, Diana M.; Ramirez, Melissa R.; Reginato, Anthony M.; Medici, Damian

    2015-01-01

    Summary Heterotopic ossification (HO) is a debilitating condition in which cartilage and bone forms in soft tissues such as muscle, tendon, and ligament causing immobility. This process is induced by inflammation associated with traumatic injury. In an extremely rare genetic disorder called fibrodysplasia ossificans progessiva (FOP), a combination of inflammation associated with minor soft tissue injuries and a hereditary genetic mutation causes massive HO that progressively worsens throughout the patients’ lifetime leading to the formation of an ectopic skeleton. An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT). In this review, we discuss the recent evidence and mechanistic data that describe the cellular and molecular mechanisms that give rise to heterotopic bone. PMID:24796520

  11. Preventative Therapeutics for Heterotopic Ossification

    DTIC Science & Technology

    2015-10-01

    formalin. The femurs were decalcified in 5% formic acid, embedded in paraffin, longitudinal sectioned (5 μm), and stained with hematoxylin- eosin...Figure 3. Histological evidence of early HO formation at the site of amputation postinjury day 7 (A-C), day 10 (D-F), and day 14 (G-I) ( Stain ...From tissue collected around the amputation site in vehicle-treated rats, hematoxylin eosin staining demonstrated endochondral ossification in

  12. The Immunological Contribution to Heterotopic Ossification Disorders

    PubMed Central

    Convente, Michael R.; Wang, Haitao; Pignolo, Robert J.; Kaplan, Frederick S.; Shore, Eileen M.

    2015-01-01

    The formation of bone outside the endogenous skeleton is a significant clinical event, rendering affected individuals with immobility and a diminished quality of life. This bone, termed heterotopic ossification (HO), can appear in patients following invasive surgeries and traumatic injuries, as well as progressively manifest in several congenital disorders. A unifying feature of both genetic and non-genetic episodes of HO is immune system involvement at the early stages of disease. Activation of the immune system sets the stage for the downstream anabolic events that eventually result in ectopic bone formation, rendering the immune system a particularly appealing site of early therapeutic intervention for optimal management of disease. In this review we will discuss the immunological contributions to HO disorders, with specific focus on contributing cell types, signaling pathways, relevant in vivo animal models, and potential therapeutic targets. PMID:25687936

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

    DTIC Science & Technology

    2015-10-01

    identify predictive markers of heterotopic ossification in an established animal model that would forecast development of heterotopic ossification (HO...4. IMPACT: Describe distinctive contributions, major accomplishments, innovations , successes, or any change in practice or behavior that has come

  14. Heterotopic Ossification in a Newborn: A Case Report

    PubMed Central

    Rand, Alohali; Abdulaziz, Jarman; Amir Mrad, Mohamed

    2016-01-01

    Introduction: Heterotopic ossification is defined as the formation of trabecular bone that forms outside the normal sites of the skeletal structure, materializing in soft tissue where it does not usually exist. Methods/Case Report: This is a case report of a 27-day-old baby with a diagnosis of DiGeorge syndrome who developed heterotopic ossification on the dorsum of his right hand. Discussion: Heterotopic ossification in the pediatric population is a rare finding. Very few cases were published in the literature, and we find it important to increase the knowledge on such cases and discuss possible causes with the treatment used with our patient. Results: General treatments of heterotopic ossification include ruling out superimposed infection, physiotherapy to prevent joint involvement, warm compressors during the active phase of development of heterotopic ossification. If the swelling persists to the point that it interferes significantly with the functional capacity of the patient or becomes a cosmetic concern, the only treatment option remaining would be surgery. PMID:28344729

  15. Heterotopic Ossification: Basic-Science Principles and Clinical Correlates.

    PubMed

    Ranganathan, Kavitha; Loder, Shawn; Agarwal, Shailesh; Wong, Victor W; Wong, Victor C; Forsberg, Jonathan; Davis, Thomas A; Wang, Stewart; James, Aaron W; Levi, Benjamin

    2015-07-01

    Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and thermal injury.➤ The conversion of progenitor cells to osteogenic precursor cells as a result of cell-mediated interactions with the local tissue environment is affected by oxygen tension, pH, availability of micronutrients, and mechanical stimuli, and leads to heterotopic ossification.➤ Radiation and certain nonsteroidal anti-inflammatory medications are important methods of prophylaxis against heterotopic ossification.➤ Well-planned surgical excision can improve patient outcomes regardless of the joint involved or the initial cause of injury.➤ Future therapeutic strategies are focused on targeted inhibition of local factors and signaling pathways that catalyze ectopic bone formation. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

  16. Proteomic Analysis of Trauma Induced Heterotopic Ossification Formation

    DTIC Science & Technology

    2015-10-01

    to identify those patients at greatest risk of HO progression during their recovery. The current project is using liquid chromatography/ mass ...military orthopaedic surgery, adipose and bone marrow stromal/stem cell biology, proteomics and mass spectroscopy, and regenerative medicine. During the...Bone Morphogenetic Protein (BMP) Fibrodysplasia Ossificans Progressiva (FOP) Heterotopic Ossification (HO) Liquid Chromatography Mass

  17. Radionuclide assessment of heterotopic ossification in spinal cord injury patients

    SciTech Connect

    Prakash, V.

    1983-01-01

    Whole body /sup 99m/T-pyrophosphate bone scans were obtained and correlated with skeletal radiographs for detection of heterotopic ossification in 135 spinal injury patients. There were 40 patients with recent injury (less than 6 months) and 95 with injury of over 6 months duration. Heterotopic new bone was detected on the bone scan in 33.7% of 95 patients with spinal cord injuries of more than 6 months duration and 30% of 40 patients with injuries of less than 6 months. The radionuclide scan was found to be useful in detection of heterotopic ossification at its early stage and in its differentiation from other complications in spinal cord injury patients.

  18. The role of endothelial-mesenchymal transition in heterotopic ossification

    PubMed Central

    Medici, Damian; Olsen, Bjorn R.

    2012-01-01

    Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called Fibrodysplasia Ossificans Progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. Here we discuss the current evidence for the endothelial contribution to heterotopic bone formation. PMID:22806925

  19. The traumatic bone: trauma-induced heterotopic ossification.

    PubMed

    Dey, Devaveena; Wheatley, Benjamin M; Cholok, David; Agarwal, Shailesh; Yu, Paul B; Levi, Benjamin; Davis, Thomas A

    2017-08-01

    Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence. Refinements of existing diagnostic modalities, like micro- and nano-CT are being adapted toward early intervention. Trauma-induced HO is a consequence of aberrant wound healing, systemic and local immune system activation, infections, extensive vascularization, and innervation. This intricate molecular crosstalk culminates in activation of stem cells that initiate heterotopic endochondral ossification. Development of animal models recapitulating the unique traumatic injuries has greatly facilitated the mechanistic understanding of trauma-induced HO. These same models also serve as powerful tools to test the efficacy of small molecules which specifically target the molecular pathways underlying ectopic ossification. This review summarizes the recent advances in the molecular understanding, diagnostic and treatment modalities in the field of trauma-induced HO. Published by Elsevier Inc.

  20. Ankylosing pelvitrochanteric heterotopic ossification in a patient with spinal cord injury.

    PubMed

    Gurcan, Serkan; Ozyurek, Selahattin; Kose, Ozkan; Sehirlioglu, Ali

    2013-05-21

    Heterotopic ossification is a frequent complication after spinal cord injury. It usually develops around major weight bearing joints. However, ankylosing hip is a rare presentation. Various treatment methods have been reported and advocated as efficacious methods for management of heterotopic ossification. We report a case of ankylosing pelvitrochanteric heterotopic ossification treated with surgical excision before full maturation, postoperative radiation therapy and indomethacine without recurrence after 1 year. Treatment options are discussed in this particular case.

  1. Extensive heterotopic ossification in patient with tubercular meningitis

    PubMed Central

    Sharma, Vijai Prakash; Yadav, Ganesh; Gupta, Anil Kumar; Kumar, Dileep

    2014-01-01

    Tubercular meningitis is a severe form of central nervous system tuberculosis with high morbidity and mortality. Apart from neurological deficits, musculoskeletal involvement is also seen in very few cases in the form of heterotopic ossification around immobile joints. A 35-year-old male case of tubercular meningitis with left hemiparesis presented with multiple joint restriction of range of motion. On clinical examination, palpable firm masses around multiple joints with painful restriction of movements were seen. X-ray films of multiple joints revealed heterotopic ossification over left shoulder, hip and knee joint with bony ankylosis of left hip and soft tissue contractures. Very few reports have been published in the literature for association of heterotopic ossification with tubercular meningitis with such extensive joint involvement which compels us to report this clinical association of tubercular meningitis. This report is intended to create caution among physicians and other caregivers for this debilitating complication of tubercular meningitis and in face of high prevalence of tuberculosis and tubercular meningitis, employ methods to prevent and treat. PMID:25540549

  2. Experimental model of heterotopic ossification in Wistar rats

    PubMed Central

    Zotz, T.G.G.; de Paula, J.B.; Moser, A.D.L.

    2012-01-01

    Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues adjacent to large joints, resulting in joint mobility deficit. In order to determine which treatment techniques are more appropriate for such condition, experimental models of induced heterotopic bone formation have been proposed using heterologous demineralized bone matrix implants and bone morphogenetic protein and other tissues. The objective of the present experimental study was to identify a reliable protocol to induce HO in Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3 different BM volumes and based on literature evidence of this HO induction model in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g were used. The animals were anesthetized for blood sampling before HO induction in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM implantation in both quadriceps muscles of these animals, experimental group (EG). Thirty-five days after the induction, another blood sample was collected for ALP determination. The results showed a weight gain in the EG and no significant difference in ALP levels when comparing the periods before and after induction. Qualitative histological analysis confirmed the occurrence of heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar rats. PMID:22473322

  3. Heterotopic ossification associated with myelopathy following cervical disc prosthesis implantation.

    PubMed

    Wenger, Markus; Markwalder, Thomas-Marc

    2016-04-01

    This case report presents a 37-year-old man with clinical signs of myelopathy almost 9 years after implantation of a Bryan disc prosthesis (Medtronic Sofamor Danek, Memphis, TN, USA) for C5/C6 soft disc herniation. As demonstrated on MRI and CT scan, spinal cord compression was caused by bony spurs due to heterotopic ossification posterior to the still moving prosthesis. The device, as well as the ectopic bone deposits, had to be removed because of myelopathy and its imminent aggravation. Conversion to anterior spondylodesis was performed.

  4. Radiation therapy for recurrent heterotopic ossification prophylaxis after partial metatarsal amputation.

    PubMed

    Boffeli, Troy J; Pfannenstein, Ryan R; Thompson, Jonathan C

    2015-01-01

    The formation of heterotopic ossification is a relatively common, yet rarely discussed, cause of re-ulceration after previous partial metatarsal amputation. Excessive bone growth at the amputation site has the potential to create an unwanted prominence on the weightbearing surface of the foot, intuitively increasing plantar pressure and placing the neuropathic patient at greater risk of re-ulceration and limb loss. The aim of the present study was to assess the efficacy of single-dose radiation therapy in preventing recurrent heterotopic ossification. The inclusion criteria consisted of a history of clinically relevant heterotopic ossification formation after partial metatarsal amputation with subsequent partial metatarsal amputation for heterotopic ossification resection, followed by prophylactic single-dose radiation therapy. Eleven consecutive patients meeting the inclusion criteria were identified for the present study. Before the intervention, 10 (91%) patients demonstrated formation of mid- to high-grade heterotopic ossification, and 9 (82%) patients exhibited an associated neuropathic ulceration. On follow-up at least 6 weeks after intervention, 2 (18%) patients exhibited low-grade heterotopic ossification reformation that was not clinically relevant and 9 (82%) did not show signs of heterotopic recurrence. Single-dose radiation therapy can help prevent the formation of heterotopic ossification in high-risk patients, acting as an effective adjunct to surgery in minimizing the risk of re-ulceration and re-amputation in the neuropathic patient.

  5. Risk Factors in Hospitalized Patients With Burn Injuries for Developing Heterotopic Ossification--A Retrospective Analysis.

    PubMed

    Orchard, Gregory R; Paratz, Jennifer D; Blot, Stijn; Roberts, Jason A

    2015-01-01

    The aims of this study were to identify the risk factors for developing heterotopic ossification in patients with burns injuries and, second, to review the outcomes associated with the treatment disodium etidronate. Patients with heterotopic ossification were identified using the burns unit computer database. The control group was the patients who were the next admission after admission of the patient who subsequently developed heterotopic ossification. Demographic and clinical data were collected. Univariate and multivariate techniques were used to identify risk factors for heterotopic ossification. We reviewed 337 patients admitted over a 5-year period and identified 19 patients with heterotopic ossification (5.6%). A further 19 burn injury patients were included as controls. Heterotopic ossification developed clinically and radiologically after a median time of 37 days (interquartile range [IQR], 30-40) and 49 days (IQR, 38-118), respectively. In univariate analysis, heterotopic ossification was associated with a greater %TBSA, inhalation injury, use of mechanical ventilation, number of surgical procedures, sepsis, and longer time to active movement. In a multivariate analysis that adjusted for severity of burn injury by means of the Belgian Outcome in Burn Injury score, time to active movement was recognized as an independent risk factor for heterotopic ossification (odds ratio 1.48, 95% confidence interval 1.09-2.01). Elevations in serum calcium concentrations were the only observed adverse effects for disodium etidonrate. This study has demonstrated that %TBSA, inhalation injury, and the need for ventilatory support and the use of multiple surgical procedures are predictive of the development of heterotopic ossification.

  6. Acquired heterotopic ossification in hips and knees following encephalitis: case report and literature review.

    PubMed

    Zhang, Xianghong; Jie, Shuo; Liu, Tang; Zhang, Xiangsheng

    2014-10-03

    Heterotopic ossification (HO) is a rare and potentially detrimental complication of soft-tissue trauma, amputations, central nervous system injury (traumatic brain injuries, spinal cord lesions, tumors, encephalitis), vasculopathies, arthroplasties and burn injury, characterized by lamellar bone growth in non-osseous tissues such as the muscle and the joint capsule. Heterotopic ossification associated with encephalitis is rare and the occurrence of excessive, symptomatic heterotopic ossification around bilateral hips and bilateral knees is rarely described in the literature. We present a 47-year-old man with heterotopic ossification in the bilateral hips and bilateral knees that prevented him from walking after being attacked by encephalitis as the case study. He developed severe pain and significantly impaired range of motion of bilateral hips and bilateral knees. Research so far revealed that the management of heterotopic ossification is controversial. After requiring revision surgery resection of heterotopic ossification, reconstruction of the medial collateral ligament and adjunctive pharmacotherapy of 200 mg Celecoxib for 8 weeks after operation, he regained mobility of his joints. On review of X-ray, there was no recurrence of HO and no loosening of rivets which were used in the reconstruction of medial collateral ligament. Heterotopic ossification in the bilateral hip joints and bilateral knee joints associated with encephalitis have never been reported previously. Daily functions of heterotopic ossification patients can be hampered by pain, inflammation, reduced mobility, the loss of normal posture and other complications. Further studies of presumptive root causes, the early diagnosis, preventability and optimal therapeutic measures for heterotopic ossification following encephalitis are required. Different patient should be managed with different appropriated protocol based on the risk of individual patient and the institutional experience.

  7. Heterotopic Ossification Secondary to Gunshot and Fragment Wounds in a Golden Eagle ( Aquila chrysaetos ).

    PubMed

    Javdani, Moosa; Hashemnia, Mohammad; Nikousefat, Zahra

    2016-03-01

    Heterotopic ossification is the process of pathologic bone formation in soft tissue structures that usually do not form bone. An immature golden eagle ( Aquila chrysaetos ) was examined 2 months after a gunshot wound in the right wing. A solid oval mass with a gun pellet at its core was found attached to the ulna by a bony pedicle and was surgically excised. Heterotopic ossification secondary to gunshot and fragment wounds in the right ulna was diagnosed based on clinical, radiographic, and histopathologic findings. This report is the first to describe heterotopic ossification occurring around a gun pellet in a bird.

  8. Effects of Radiation Therapy on Established Neurogenic Heterotopic Ossification

    PubMed Central

    2016-01-01

    Heterotopic ossification (HO) is frequently seen on rehabilitation units after spinal cord injuries, fractures, brain injuries, and limb amputations. Currently, there is no effective treatment for HO other than prophylaxis with anti-inflammatory medications, irradiation, and bisphosphonate administration. These prophylactic treatments are not effective for managing ectopic bone once it has formed. Here we describe three cases of established neurogenic HO treated with radiation therapy (RT). All patients had decreased serum alkaline phosphatase (ALP) and bone-specific ALP levels with decreased pain but increased range of motion immediately after RT. Post-treatment X-rays revealed no further growth of the HO. All patients maintained clinical and laboratory improvements 4 or 6 months after the RT. Our results suggest that RT is safe and effective in decreasing pain and activity of neurogenic HO. PMID:28119846

  9. Heterotopic ossification of the elbows in a major petrol burn

    PubMed Central

    Zaman, Shahriar Raj

    2012-01-01

    A case of a young man who developed heterotopic ossification (HO) in his elbows following an accident where he sustained petrol burns to over 60% of his body. His injuries necessitated intubation, escharotomies and a protracted intensive care unit stay that was complicated by septicaemia. Several weeks after the injury, he was diagnosed with HO in his right elbow, followed by the left elbow a week later. He was commenced on an non-steroidal anti-inflammatory drug, a long-term course of a bisphosphonate and regular physiotherapy. He is now waiting for the HO bone to mature before having definitive excision of his lesions in 12-18 months time. PMID:22927269

  10. Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification

    PubMed Central

    Loder, Shawn; Agarwal, Shailesh; Sorkin, Michael; Breuler, Chris; Li, John; Peterson, Joshua; Hsieh, Hsiao Hsin Sung; Wang, Stewart; Mehrara, Babak; Levi, Benjamin

    2016-01-01

    Objective The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification. Background Heterotopic ossification (HO) is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is up-regulated during incidents of trauma, thereby co-incident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation. Methods Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO. Results Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% v. 0.8%, p<0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% v. 3.3%, p<0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2−/CD45−/CD90−/BP1−) were also significantly decreased after lymph node excision (10.2% v. 0.5%, p<0.05). A significant decrease was noted in the volume of de novo HO present within the soft tissues (0.12 mm^3 v. 0.02 mm^3). Conclusions These findings suggest that lymphatic vessels are intimately linked with the formation de novo bone within soft tissues following trauma, and their presence may facilitate bone formation. PMID:26779981

  11. 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. ...

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

    DTIC Science & Technology

    2016-03-01

    1 Award Number: W81XWH-14-2-0010 TITLE: Combat-Related Heterotopic Ossification: Development of Animal Models for Identifying Mechanisms and...June 2014 - 14 December 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Combat-Related Heterotopic Ossification: Development of Animal Models for...etiology, treatment, and prevention is the absence of a reliable and reproducible small animal model that can be used to characterize combat‐related HO

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

    DTIC Science & Technology

    2015-10-01

    NOTES 14. ABSTRACT The purpose of this project is to identify predictive markers of heterotopic ossification in an established animal model that would...forecast development of heterotopic ossification (HO) in humans soon after injury. Blast procedures have been completed on all 30 animals (Groups I...II) in the year 1 SOW and 45 animals (Groups III – V) in the year 2 SOW. All animals were biopsied and have been sacrificed according to protocol

  14. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy.

    PubMed

    Drane, W E; Tipler, B M

    1987-06-01

    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  15. Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

    SciTech Connect

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A. )

    1990-12-01

    Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.

  16. Neurogenic heterotopic ossification: epidemiology and morphology on conventional radiographs in an early neurological rehabilitation population.

    PubMed

    Seipel, R; Langner, S; Platz, T; Lippa, M; Kuehn, J P; Hosten, N

    2012-01-01

    To retrospectively evaluate neurogenic heterotopic ossification in an early neurological rehabilitation population (phases B and C) with respect to epidemiology and morphology on conventional radiographs. Over a 4-year period, 1,463 patients treated at a clinic for early neurological rehabilitation were evaluated for clinical symptoms of neurogenic heterotopic ossification. In case of clinical suspicion, plain radiographs of the expected sites were obtained. If heterotopic ossification was detected, the initial and subsequent radiographs were retrospectively analyzed for sites, size, and morphology. Immature lesions were categorized as small (<10 mm) or large (10-100 mm). The prevalence rate of neurogenic heterotopic ossification was 2.05%. The condition was most common in young male adults. The hip was the most common site accounting for more than half of the cases. Two or more ossifications were seen in 56.7% of the affected patients with approximately two-thirds showing bilateral symmetric involvement of corresponding joint regions. The size of ossifications strongly varied interindividually. Small immature lesions demonstrated less progression in size than large lesions during maturation (P < 0.05). Standard radiographs, as a fast and inexpensive technique, allow the expected size progression of heterotopic ossifications during maturation to be estimated, which is relevant in terms of therapeutic decisions, patient mobilization, and neurological rehabilitation.

  17. Heterotopic mineralization (ossification or calcification) in tendinopathy or following surgical tendon trauma

    PubMed Central

    O'Brien, Etienne J O; Frank, Cyril B; Shrive, Nigel G; Hallgrímsson, Benedikt; Hart, David A

    2012-01-01

    Heterotopic tendon mineralization (ossification or calcification), which may be a feature of tendinopathy or which may develop following surgical trauma (repair or graft harvest), has not received much attention. The purpose of this article is to review the prevalence, mechanisms and consequences of heterotopic tendon mineralization and to identify the gaps in our current understanding. We focus on endochondral heterotopic ossification and draw on knowledge of the mechanisms of this process in other tissues and conditions. Finally, we introduce a novel murine Achilles tendon needle injury model, which will enable us to further study the mechanisms and biomechanical consequences of tendon mineralization. PMID:22974213

  18. Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

    PubMed Central

    Papanagiotou, Marianthi; Dailiana, Zoe H; Karachalios, Theophilos; Varitimidis, Sokratis; Hantes, Michael; Dimakopoulos, Georgios; Vlychou, Marianna; Malizos, Konstantinos N

    2017-01-01

    AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of nonunions. METHODS Bone morphogenetic proteins (BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients (80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent joints were also carried out. Factors related to the patient (age, gender), the nonunion (location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure (graft and fixation type, amount of rhBMP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ2 test was performed. RESULTS Eighty point nine percent of the nonunions treated with rhBMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients (17.8%) and it was apparent in the routine radiological evaluation of the nonunion site, in a mean time of 5.5 mo after the rhBMP-7 application (range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhBMP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient’s gender was the only important factor for the development of heterotopic ossification (P = 0.007). CONCLUSION Heterotopic ossification after the use of rhBMP-7 in nonunions was

  19. Heterotopic ossification of the elbow after closed reduction and retrograde intramedullary nailing for radial neck fracture treated by anconeus interposition.

    PubMed

    Sreenivas, T; Menon, Jagdish; Nataraj, A R

    2013-12-01

    Heterotopic ossification around the elbow can lead to considerable functional disability. We describe a case of a 42-year-old man who developed heterotopic ossification of his elbow after closed reduction of the elbow dislocation and radial neck fracture and retrograde intramedullary nailing for radial neck fracture. During the follow-up after initial surgery, movements of the elbow were gradually deteriorated and diagnosed as heterotopic ossification of the elbow. Implant removal, radial head excision along with heterotopic mass, and also interposition of the anconeus muscle resulted in improvement of his elbow mobility. At 18 months of follow-up, patient had elbow flexion arc of 15°-110°, 70° of supination, and 50° of pronation without recurrence of heterotopic ossification. The uniqueness of this case lies in the treatment of heterotopic ossification of the elbow to prevent its recurrence, which was developed after retrograde intramedullary nailing for radial neck fracture following closed reduction.

  20. Inhibition of connexin 43 prevents trauma-induced heterotopic ossification

    PubMed Central

    Tu, Bing; Liu, Shen; Liu, Guangwang; Li, Zhiwei; Sun, Yangbai; Fan, Cunyi

    2016-01-01

    Heterotopic ossification (HO) can result from traumatic injury, surgery or genetic diseases. Here, we demonstrate that overexpression of connexin 43 (Cx43) is critical for the development and recurrence of traumatic HO in patients. Inhibition of Cx43 by shRNA substantially suppressed the osteogenic differentiation of MC-3T3 cells and the expression of osteogenic genes. We employed a tenotomy mouse model to explore the hypothesis that Cx43 is vital to the development of HO. Inhibition of Cx43 by a specific shRNA decreased extraskeletal bone formation in vivo. In addition, we demonstrated that ERK signaling activated by Cx43 plays an important role in promoting HO. ERK signaling was highly activated in HO tissue collected from patient and mouse models. Importantly, de novo soft tissue HO was significantly attenuated in mice treated with U0126. Inhibition of Cx43 and ERK led to decreased expressions of Runx2, BSP and Col-1 in vivo and in vitro. Moreover, HO patients with low Cx43 expression or ERK activation had a lower risk of recurrence after the lesions were surgically removed. Our findings indicate that Cx43 promotes trauma-induced HO formation by activating the ERK pathway and enhances the expression of osteogenic markers. PMID:27849058

  1. Substance P Signaling Mediates BMP Dependent Heterotopic Ossification

    PubMed Central

    Kan, Lixin; Lounev, Vitali Y; Pignolo, Robert J; Duan, Lishu; Liu, Yijie; Stock, Stuart R; McGuire, Tammy L; Lu, Bao; Gerard, Norma P; Shore, Eileen M; Kaplan, Frederick S; Kessler, John A

    2012-01-01

    Heterotopic ossification (HO) is a disabling condition associated with neurologic injury, inflammation, and overactive BMP signaling. The inductive factors involved in lesion formation are unknown. We found that the expression of the neuro-inflammatory factor Substance P (SP) is dramatically increased in early lesional tissue in patients who have either fibrodysplasia ossificans progressiva (FOP) or acquired HO, and in three independent mouse models of HO. In Nse-BMP4, a mouse model of HO, robust HO forms in response to tissue injury; however null mutations of the preprotachykinin gene encoding SP prevent HO. Importantly, ablation of SP+ sensory neurons, treatment with an antagonist of SP receptor NK1r, deletion of NK1r gene, or genetic down-regulation of NK1r-expressing mast cells also profoundly inhibits injury-induced HO. These observations establish a potent neuro-inflammatory induction and amplification circuit for BMP-dependent HO lesion formation, and identify novel molecular targets for prevention of HO. PMID:21748788

  2. A clinical perspective on common forms of acquired heterotopic ossification

    SciTech Connect

    Garland, D.E. )

    1991-02-01

    The clinical courses of heterotopic ossification (HO) as a consequence of trauma and central nervous system insults have many similarities as well as dissimilarities. Detection is commonly noted at two months. The incidence of clinically significant HO is 10%-20%. Approximately 10% of the HO is massive and causes severe restriction in joint motion or ankylosis. The most common sign and symptom are decreased range of motion and pain. The locations are the proximal limbs and joints. Sites of HO about a joint may vary according to the etiology of the HO. Roentgenographic evolution of HO occurs during a six-month period in the majority of patients. Treatment modalities include diphosphonates, indomethacin, radiation, range of motion exercises, and surgical excision. Surgical timing differs according to etiology: traumatic HO may be resected at six months; spinal cord injury HO is excised at one year; and traumatic brain injury HO is removed at 1.5 years. A small number of patients have progression of HO with medicinal treatment and recurrence after resection. The patients seem recalcitrant to present treatment methods regardless of the HO etiology. 117 refs.

  3. Extensive Abdominal Wall Incisional Heterotopic Ossification Reconstructed with Component Separation and Strattice Inlay

    PubMed Central

    Suleiman, Nergis Nina

    2016-01-01

    Summary: Symptomatic heterotopic ossification of abdominal surgical incisions is a rare occurrence. We present a 67-year-old man with severe discomfort caused by heterotopic ossification extending from the xiphoid to the umbilicus. The patient underwent an abdominal aortic aneurysm repair 3 years before our treatment. A 13 × 3.5 cm ossified lesion was excised. The resulting midline defect was closed using component separation and inlay Strattice. Tension-free midline adaptation of the recti muscles was achieved. A computed tomography scan of the abdomen 6 months after the surgery showed no recurrence or hernias. Heterotopic ossification in symptomatic patients has previously been treated with excision and primary closure. We believe that tension-free repair is important to prevent recurrence. Acellular dermal matrix may add to this effect and also compartmentalize the process. PMID:27536495

  4. The Impact of Body Mass Index on Heterotopic Ossification

    SciTech Connect

    Mourad, Waleed Fouad; Packianathan, Satya; Shourbaji, Rania A.; Zhang Zhen; Graves, Mathew; Khan, Majid A.; Baird, Michael C.; Russell, George; Vijayakumar, Srinivasan

    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 {+-} indomethacin 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.

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

    DTIC Science & Technology

    2016-03-01

    fitting and function, a need for surgical revision of the residual limb, and delayed rehabilitation. Heterotopic ossification is the pathologic ...the offending bone rather than primary prevention. Investigation of the effects of blast trauma on the musculoskeletal system, specifically the...Lavage of Open Musculoskeletal Wounds Causes Muscle Necrosis and Dystrophic Calcification” o AAOS EWI Symposium (2/2014 - poster); “Failure of

  6. Risk Factors Associated with Diagnoses of Heterotopic Ossification in Recent Combat Amputees

    DTIC Science & Technology

    2009-07-22

    complications13-23, such as infections, phantom limb syndrome , deep vessel thrombosis, and pulmonary embolism have not received systematic study as possible...the overall difference was not significant. However, phantom limb syndrome and infections, such as osteomyelitis and chronic infection of the...higher overall rates in heterotopic ossification patients ( phantom limb syndrome , osteomyelitis, chronic infection, deep vessel thrombosis, pulmonary

  7. Is preoperative radiation therapy as effective as postoperative radiation therapy for heterotopic ossification prevention in acetabular fractures?

    PubMed

    Archdeacon, Michael T; d'Heurle, Albert; Nemeth, Nicole; Budde, Bradley

    2014-11-01

    Prophylactic approaches to prevent heterotopic ossification after acetabular fracture surgery have included indomethacin and/or single-dose external beam radiation therapy administered after surgery. Although preoperative radiation has been used for heterotopic ossification prophylaxis in the THA population, to our knowledge, no studies have compared preoperative and postoperative radiation therapy in the acetabular fracture population. We determined whether heterotopic ossification frequency and severity were different between patients with acetabular fracture treated with prophylactic radiation therapy preoperatively and postoperatively. Between January 2002 and December 2009, we treated 320 patients with a Kocher-Langenbeck approach for acetabular fractures, of whom 50 (34%) were treated with radiation therapy preoperatively and 96 (66%) postoperatively. Thirty-four (68%) and 71 (74%), respectively, had 6-month radiographs available for review and were included. For hospital logistical reasons, patients who underwent operative treatment on a Friday or Saturday received radiation therapy preoperatively, and all others received it postoperatively. The treatment groups were comparable in terms of most demographic parameters, injury severity, and fracture patterns. Six-month postoperative radiographs were reviewed and graded according to Brooker. Followup ranged from 6 to 93 months and 6 to 97 months for the preoperative and postoperative groups, respectively. Post hoc power analysis showed our study was powered to detect a difference of 22% or more between patients with severe heterotopic ossification. Sample size calculations showed 915 subjects would be needed to detect a 5% relative difference in severe heterotopic ossification status between groups. We detected no difference in heterotopic ossification frequency between the preoperative (eight of 36, 22%) and postoperative (19 of 71, 27%) groups (p=0.609). There was also no difference in heterotopic

  8. MiR-630 Inhibits Endothelial-Mesenchymal Transition by Targeting Slug in Traumatic Heterotopic Ossification

    PubMed Central

    Sun, Yangbai; Cai, Jiangyu; Yu, Shiyang; Chen, Shuai; Li, Fengfeng; Fan, Cunyi

    2016-01-01

    Heterotopic ossification (HO) is the abnormal formation of mature bone in extraskeletal soft tissues that occurs as a result of inflammation caused by traumatic injury or associated with genetic mutation. Despite extensive research to identify the source of osteogenic progenitors, the cellular origins of HO are controversial and the underlying mechanisms, which are important for the early detection of HO, remain unclear. Here, we used in vitro and in vivo models of BMP4 and TGF-β2-induced HO to identify the cellular origin and the mechanisms mediating the formation of ectopic bone in traumatic HO. Our results suggest an endothelial origin of ectopic bone in early phase of traumatic HO and indicate that the inhibition of endothelial-mesenchymal transition by miR-630 targeting Slug plays a role in the formation of ectopic bone in HO. A matched case-control study showed that miR-630 is specifically downregulated during the early stages of HO and can be used to distinguish HO from other processes leading to bone formation. Our findings suggest a potential mechanism of post-traumatic ectopic bone formation and identify miR-630 as a potential early indicator of HO. PMID:26940839

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

    DTIC Science & Technology

    2012-10-01

    injured amputated extremity. We hypothesize that systemic administration of Naproxen sodium, with a 24 hour delay in institution of therapy after... therapy , 800cGy delivered within 72 hours of injury, will substantially diminish heterotopic ossification in the injured limb stump. Statement of...Work, Task 6: (Phase III) Investigate the influence of NSAID therapy on the prevalence and severity of HO. Perform hind limb blast protocol with

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

    DTIC Science & Technology

    2016-10-01

    analysis of animal biopsy specimens was performed by the Nesti partner lab in order to identify molecular predictors of HO. qRT-PCR and Western blot...AWARD NUMBER: W81XWH-13-2-0084 TITLE: Early Identification of Molecular Predictors of Heterotopic Ossification Following Extremity Blast...2016 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2015 – 29 Sep 2016 4. TITLE AND SUBTITLE Early Identification of Molecular Predictors of

  11. Characterization of Cells Isolated from Genetic and Trauma-Induced Heterotopic Ossification

    PubMed Central

    Agarwal, Shailesh; Drake, James; Qureshi, Ammar T.; Loder, Shawn; Li, Shuli; Shigemori, Kay; Peterson, Jonathan; Cholok, David; Forsberg, Jonathan A.; Mishina, Yuji; Davis, Thomas A.; Levi, Benjamin

    2016-01-01

    Heterotopic ossification (HO) is the pathologic formation of bone separate from the normal skeleton. Although several models exist for studying HO, an understanding of the common in vitro properties of cells isolated from these models is lacking. We studied three separate animal models of HO including two models of trauma-induced HO and one model of genetic HO, and human HO specimens, to characterize the properties of cells derived from tissue containing pre-and mature ectopic bone in relation to analogous mesenchymal cell populations or osteoblasts obtained from normal muscle tissue. We found that when cultured in vitro, cells isolated from the trauma sites in two distinct models exhibited increased osteogenic differentiation when compared to cells isolated from uninjured controls. Furthermore, osteoblasts isolated from heterotopic bone in a genetic model of HO also exhibited increased osteogenic differentiation when compared with normal osteoblasts. Finally, osteoblasts derived from mature heterotopic bone obtained from human patients exhibited increased osteogenic differentiation when compared with normal bone from the same patients. These findings demonstrate that across models, cells derived from tissues forming heterotopic ossification exhibit increased osteogenic differentiation when compared with either normal tissues or osteoblasts. These cell types can be used in the future for in vitro investigations for drug screening purposes. PMID:27494521

  12. [The use of radiotherapy in the prevention of heterotopic ossification in patients with total hip replacement].

    PubMed

    Marziano, C; Pichi, E; Chiarlone, R; Luzi, G; Siccardi, C

    1996-12-01

    In order to prevent heterotopic ossification (HO) after total hip replacement, 21 high risk hips were irradiated pre- and postoperatively to prevent heterotopic bone formation in the St. Paul Department of Radiation Oncology from 1993 to September, 1995. Eighteen hips in 15 patients were eligible for analysis with a minimum follow-up of 3 months. All the hips in our series were at high risk of heterotopic bone formation. All assessable patients had radiographic findings of ipsilateral or contralateral previous ectopic bone formation, 8 following total hip arthroplasty, 4 following trauma and 3 had heterotopic osteoarthritis. Four hips were treated 46 hours preoperatively, while all the others were treated on the first postoperative day. The irradiation field was limited to the hip region and radiation exposure to a rectangular field, ranging in size from 8 x 12 to 10 x 15 cm, to include the lateral aspect of the greater trochanter. We used a cobalt-60 unit. Opposed anterior-posterior fields were irradiated at midplan, with a source-to-axis distance of 80 cm; the dose was 6-8 Gy in one fraction. Preoperative irradiation appeared as effective as postoperative treatment, and more comfortable for the patients. There were neither side-effects nor failure of ossification. The treatment appeared effective in the prophylaxis of HO in 88% of patients, with clinical advantages in 67% of them.

  13. Radiation therapy for heterotopic ossification prophylaxis acutely after elbow trauma: a prospective randomized study.

    PubMed

    Hamid, Nady; Ashraf, Nomaan; Bosse, Michael J; Connor, Patrick M; Kellam, James F; Sims, Stephen H; Stull, Douglass E; Jeray, Kyle J; Hymes, Robert A; Lowe, Timothy J

    2010-09-01

    Heterotopic ossification around the elbow can result in pain, loss of motion, and impaired function. We hypothesized that a single dose of radiation therapy could be administered safely and acutely after elbow trauma, could decrease the number of elbows that would require surgical excision of heterotopic ossification, and might improve clinical results. A prospective randomized study was conducted at three medical centers. Patients with an intra-articular distal humeral fracture or a fracture-dislocation of the elbow with proximal radial and/or ulnar fractures were enrolled. Patients were randomized to receive either single-fraction radiation therapy of 700 cGy immediately postoperatively (within seventy-two hours) or nothing (the control group). Clinical and radiographic assessment was performed at six weeks, three months, and six months postoperatively. All adverse events and complications were documented prospectively. This study was terminated prior to completion because of an unacceptably high number of adverse events reported in the treatment group. Data were available on forty-five of the forty-eight patients enrolled in this study. When the rate of complications was investigated, a significant difference was detected in the frequency of nonunion between the groups. Of the nine patients who had a nonunion, eight were in the treatment group. The nonunion rate was 38% (eight) of twenty-one patients in the treatment group, which was significantly different from the rate of 4% (one) of twenty-four patients in the control group (p = 0.007). There were no significant differences between the groups with regard to the prevalence of heterotopic ossification, postoperative range of motion, or Mayo Elbow Performance Score noted at the time of study termination. This study demonstrated that postoperative single-fraction radiation therapy, when used acutely after elbow trauma for prophylaxis against heterotopic ossification, may play a role in increasing the rate of

  14. Heterotopic ossification in complex orthopaedic combat wounds: quantification and characterization of osteogenic precursor cell activity in traumatized muscle.

    PubMed

    Davis, Thomas A; O'Brien, Frederick P; Anam, Khairul; Grijalva, Steven; Potter, Benjamin K; Elster, Eric A

    2011-06-15

    Heterotopic ossification frequently develops following high-energy blast injuries sustained in modern warfare. We hypothesized that differences in the population of progenitor cells present in a wound would correlate with the subsequent formation of heterotopic ossification. We obtained muscle biopsy specimens from military service members who had sustained high-energy wartime injuries and from patients undergoing harvest of a hamstring tendon autograft. Plastic-adherent cells were isolated in single-cell suspension and plated to assess the prevalence of colony-forming cells. Phenotypic characteristics were assessed with use of flow cytometry. Individual colony-forming units were counted after an incubation period of seven to ten days, and replicate cultures were incubated in lineage-specific induction media. Immunohistochemical staining was then performed to determine the percentage of colonies that had differentiated along an osteogenic lineage. Quantitative real-time reverse-transcription polymerase chain reaction was used to identify changes in osteogenic gene expression. Injured patients had significantly higher numbers of muscle-derived connective-tissue progenitor cells per gram of tissue (p < 0.0001; 95% confidence interval [CI], 129,930 to 253,333), and those who developed heterotopic ossification had higher numbers of assayable osteogenic colonies (p < 0.016; 95% CI, 12,249 to 106,065). In the injured group, quantitative real-time reverse-transcription polymerase chain reaction performed on the in vitro expanded progeny of connective-tissue progenitors demonstrated upregulation of COL10A1, COL4A3, COMP, FGFR2, FLT1, IGF2, ITGAM, MMP9, PHEX, SCARB1, SOX9, and VEGFA in the patients with heterotopic ossification as compared with those without heterotopic ossification. Our study suggests that the number of connective-tissue progenitor cells is increased in traumatized tissue. Furthermore, wounds in which heterotopic ossification eventually forms have a higher

  15. Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification

    PubMed Central

    Yuasa, Masato; Mignemi, Nicholas A.; Nyman, Jeffry S.; Duvall, Craig L.; Schwartz, Herbert S.; Okawa, Atsushi; Yoshii, Toshitaka; Bhattacharjee, Gourab; Zhao, Chenguang; Bible, Jesse E.; Obremskey, William T.; Flick, Matthew J.; Degen, Jay L.; Barnett, Joey V.; Cates, Justin M.M.; Schoenecker, Jonathan G.

    2015-01-01

    Bone formation during fracture repair inevitably initiates within or around extravascular deposits of a fibrin-rich matrix. In addition to a central role in hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory and mesenchymal progenitor egress into the zone of injury. However, given that a failure of efficient fibrin clearance can impede normal wound repair, the precise contribution of fibrin to bone fracture repair, whether supportive or detrimental, is unknown. Here, we employed mice with genetically and pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin-degrading plasminogen to explore the hypothesis that fibrin is vital to the initiation of fracture repair, but impaired fibrin clearance results in derangements in bone fracture repair. In contrast to our hypothesis, fibrin was entirely dispensable for long-bone fracture repair, as healing fractures in fibrinogen-deficient mice were indistinguishable from those in control animals. However, failure to clear fibrin from the fracture site in plasminogen-deficient mice severely impaired fracture vascularization, precluded bone union, and resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion in plasminogen-deficient animals restored a normal pattern of fracture repair and substantially limited heterotopic ossification. Fibrin is therefore not essential for fracture repair, but inefficient fibrinolysis decreases endochondral angiogenesis and ossification, thereby inhibiting fracture repair. PMID:26214526

  16. Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2.

    PubMed

    Krishnan, Laxminarayanan; Priddy, Lauren B; Esancy, Camden; Klosterhoff, Brett S; Stevens, Hazel Y; Tran, Lisa; Guldberg, Robert E

    2017-02-01

    Bone morphogenetic protein-2 (BMP-2), delivered on absorbable collagen sponge, is frequently used to treat bone defects. However, supraphysiological BMP-2 doses are common and often associated with complications such as heterotopic ossification and inflammation, causing pain and impaired mobility. This has prompted investigations into strategies to spatially control bone regeneration, for example growth factor delivery in appropriate scaffolds. Our objective was to investigate the spatiotemporal effects of high dose BMP-2 on bone regeneration as a function of the delivery vehicle. We hypothesized that an alginate delivery system would spatially restrict bone formation compared to a collagen sponge delivery system. In vitro, BMP-2 release was accelerated from collagen sponge compared to alginate constructs. In vivo, bone regeneration was evaluated over 12weeks in critically sized rat femoral segmental defects treated with 30μg rhBMP-2 in alginate hydrogel or collagen sponge, surrounded by perforated nanofiber meshes. Total bone volume, calculated from micro-CT reconstructions, was higher in the alginate group at 12weeks. Though bone volume within the central defect region was greater in the alginate group at 8 and 12weeks, heterotopic bone volume was similar between groups. Likewise, mechanical properties from ex vivo torsional testing were comparable between groups. Histology corroborated these findings and revealed heterotopic mineralization at 2weeks post-surgery in both groups. Overall, this study recapitulated the heterotopic ossification associated with high dose BMP-2 delivery, and demonstrated that the amount and spatial pattern of bone formation was dependent on the delivery matrix.

  17. Intracerebral haemorrhage and hemiplegia with heterotopic ossification of the affected hip.

    PubMed

    O'Brien, M M C; Murray, T; Keeling, F; Williams, D

    2015-08-04

    We present the case of a 72-year-old woman who developed right hemiparesis following a left frontal intraparenchymal haemorrhage. Three months following initial presentation, the patient noted poorly localised right lower quadrant pain. Following extensive investigations, a diagnosis of heterotopic ossification of the hip was made. We discuss the aetiology and pathogenesis of this uncommon entity, and discuss its relationship to ipsilateral neurological injury. The link with neurological injury can result in a delayed and atypical presentation. Early recognition and treatment are important for those caring for patients with acquired neurological deficits, and permit improved patient outcomes.

  18. The use of spect/ct in the evaluation of heterotopic ossification in para/tetraplegics

    PubMed Central

    Lima, Maurício Coelho; Passarelli, Marcus Ceregati; Dario, Virgílio; Lebani, Bruno Rodrigues; Monteiro, Paulo Henrique Silva; Ramos, Celso Darío

    2014-01-01

    Objective: To evaluate the stage of maturation and the metabolism of neurogenic heterotopic ossification by using SPECT/CT. Methods: A total of 12 medical records of patients with spinal cord injury, all of them classified according to the ASIA protocol (disability scale from the American Spinal Injury Association) in complete lesion (A) and partial lesions (B, C and D) and registered at the Laboratory of Biomechanics and Rehabilitation of the Locomotor System, were submitted to SPECT/CT evaluation. Results: Sixteen hips with heterotopic ossification observed in X-ray were studied and only two (12.5%) had high osteoblastic activity. Five hips showed medium activity, three (18.75%) low activity and six (37.5%) did not present any activity detected by SPECT/CT. Conclusion: SPECT/CT helps to determinate which patients have a greater risk of relapse after surgical resection, proving to be a useful imaging study in preoperative evaluation that can be used to determinate the postoperative prognosis of these patients. Level of Evidence III, Investigating a Diagnostic Test. PMID:24644413

  19. The value of serum creatine kinase in early diagnosis of heterotopic ossification.

    PubMed

    Sherman, Andrew L; Williams, Joan; Patrick, Lornette; Banovac, Kresimir

    2003-01-01

    Heterotopic ossification (HO) is a complication of spinal cord injury (SCI) characterized by formation of ectopic bone. Early diagnosis is critical, but available diagnostic methods have drawbacks. Serum creatine kinase may be a marker for the development and severity of HO. 18 SCI patients with diagnosed HO based on clinical findings and bone scintigraphy. Serum creatine kinase levels were taken at the time of diagnosis of HO and during subsequent etidronate therapy. Of the 14 patients with normal creatine kinase values, 13 had no evidence of HO on follow-up radiographic examination. Of the 4 patients with elevated creatine kinase, all developed radiographic signs of HO. Elevated serum creatine kinase may be associated with a more aggressive course of HO as well as resistance to etidronate therapy. Further studies are needed to determine whether creatine kinase may serve as a marker for early, active HO.

  20. Heterotopic Ossification of the Calvarium Following Bilateral Craniectomies in Traumatic Brain Injury

    PubMed Central

    Vega, Rafael A.; Hutchins, Leslie

    2017-01-01

    Background: Heterotopic ossification (HO) is defined as ectopic bone formation following traumatic brain injury. Patients typically develop lesions in the hips, knees, and elbows that cause pain, restricted range of motion, nerve impingement, and pressure ulcers. Case Report: We report an unusual presentation of HO in an 18-year-old male who was involved in a motor vehicle accident and subsequently developed malignant intracranial pressure. His HO developed following bilateral craniectomies in which 2 different dural substitutes were used. Radiographic timing of ectopic bone formation and its continued growth varied. Conclusion: We describe a case of HO in the cranium, a condition that is underreported in the literature. Of significance, despite sustaining multiple traumatic fractures that were managed conservatively, our patient failed to demonstrate any evidence of ectopic axial HO following his incident. PMID:28331459

  1. Heterotopic ossification: Pathophysiology, clinical features, and the role of radiotherapy for prophylaxis

    SciTech Connect

    Balboni, Tracy A.; Gobezie, Reuben; Mamon, Harvey J. . E-mail: hmamon@partners.org

    2006-08-01

    Heterotopic ossification (HO) is a benign condition of abnormal formation of bone in soft tissue. HO is frequently asymptomatic, though when it is more severe it typically manifests as decreased range of motion at a nearby joint. HO has been recognized to occur in three distinct contexts-trauma, neurologic injury, and genetic abnormalities. The etiology of HO is incompletely understood. A posited theory is that HO results from the presence of osteoprogenitor cells pathologically induced by an imbalance in local or systemic factors. Individuals at high risk for HO development frequently undergo prophylaxis to prevent HO formation. The two most commonly employed modalities for prophylaxis are nonsteroidal anti-inflammatory drugs and radiation therapy. This review discusses HO pathophysiology, clinical features, and the role of radiotherapy for prophylaxis.

  2. Effect of heterotopic ossification on hip range of motion and clinical outcome.

    PubMed

    Vasileiadis, George I; Amanatullah, Derek F; Crenshaw, Jeremy R; Taunton, Michael J; Kaufman, Kenton R

    2015-03-01

    The utility of heterotopic ossification (HO) classification systems is debatable. The range of motion and Harris hip score (HHS) were calculated in 104 patients with known HO after total hip arthroplasty and 208 matched controls without HO. The patients with HO were radiographically divided into high and low grade HO groups. There was no statistically significant association of HHS with high or low grade HO. High grade HO had a statistically significant 6° loss of terminal hip flexion, 4° loss of abduction, and 6° loss of internal rotation at the hip. The small changes in terminal hip range of motion and lack of association with HHS may be the result of false radiographic continuity resulting in an overestimation of the disability in high grade HO. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle.

    PubMed

    Genêt, François; Kulina, Irina; Vaquette, Cedryck; Torossian, Frédéric; Millard, Susan; Pettit, Allison R; Sims, Natalie A; Anginot, Adrienne; Guerton, Bernadette; Winkler, Ingrid G; Barbier, Valérie; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline; Hutmacher, Dietmar W; Levesque, Jean-Pierre

    2015-06-01

    Neurological heterotopic ossification (NHO) is the abnormal formation of bone in soft tissues as a consequence of spinal cord or traumatic brain injury. NHO causes pain, ankyloses, vascular and nerve compression and delays rehabilitation in this high-morbidity patient group. The pathological mechanisms leading to NHO remain unknown and consequently there are no therapeutic options to prevent or reduce NHO. Genetically modified mouse models of rare genetic forms of heterotopic ossification (HO) exist, but their relevance to NHO is questionable. Consequently, we developed the first model of spinal cord injury (SCI)-induced NHO in genetically unmodified mice. Formation of NHO, measured by micro-computed tomography, required the combination of both SCI and localized muscular inflammation. Our NHO model faithfully reproduced many clinical features of NHO in SCI patients and both human and mouse NHO tissues contained macrophages. Muscle-derived mesenchymal progenitors underwent osteoblast differentiation in vitro in response to serum from NHO mice without additional exogenous osteogenic stimuli. Substance P was identified as a candidate NHO systemic neuropeptide, as it was significantly elevated in the serum of NHO patients. However, antagonism of substance P receptor in our NHO model only modestly reduced the volume of NHO. In contrast, ablation of phagocytic macrophages with clodronate-loaded liposomes reduced the size of NHO by 90%, supporting the conclusion that NHO is highly dependent on inflammation and phagocytic macrophages in soft tissues. Overall, we have developed the first clinically relevant model of NHO and demonstrated that a combined insult of neurological injury and soft tissue inflammation drives NHO pathophysiology. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. Pseudo-Acetabulum due to Heterotopic Ossification in a Child with Post Traumatic Neglected Posterior Hip Dislocation

    PubMed Central

    Pathak, Aditya C; Patil, Atul K; Sheth, Binoti; Bansal, Rohan

    2012-01-01

    Introduction: Traumatic neglected dislocations of hip in children are rare entity. Neglected traumatic dislocations of hip in children along with heterotopic ossification are still rare. Post traumatic neglected hip dislocations are to be diagnosed as early as possible and have to be treated with precision and aggression as the outcome of treatment for the same is not predictable. Case Report: 5 year female with post-traumatic neglected hip dislocation with heterotopic ossification forming a pseudoacetabulum postero-superiorly in which femur head was lodged. The girl was operated by open reduction using Moore’s Posterior approach and showed good results. Here is a mention of a rare case with a good 18 months follow up with no complication. Conclusions: Post-traumatic neglected posterior hip dislocation mostly requires open reduction and relocation of femoral head in original acetabulum with concentric reduction. Heterotopic ossification is a rare but known complication of traumatic dislocation of hip in children. Good results can be achieved in such cases and regular follow-up of patient is required post-operatively.

  5. Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty.

    PubMed

    Freeman, Theresa A; Parvizi, Javad; Dela Valle, Craig J; Steinbeck, Marla J

    2010-09-01

    Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress. The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species. Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA.

  6. Risk factors for development of heterotopic ossification of the elbow after fracture fixation.

    PubMed

    Abrams, Geoffrey D; Bellino, Michael J; Cheung, Emilie V

    2012-11-01

    Postoperative heterotopic ossification (HO) about the elbow may occur after surgical fixation of fractures and can contribute to dysfunction. Factors associated with HO formation after surgical fixation of elbow trauma are not well understood. All patients who underwent surgery for elbow trauma at our institution from October 2001 through August 2010 were retrospectively reviewed. Patients with prior injury or deformity to the involved elbow were excluded. Demographic data; fracture type; surgical treatment; and presence, location, and size of HO were recorded. The Fisher exact test, χ(2) test, and multivariate logistic regression were used with an α value of .05 used for significance. A total of 159 patients were identified, with 89 (37 men and 52 women) meeting inclusion and exclusion criteria. The mean age was 54.4 years (range, 18-90 years), and the mean follow-up time was 180 days. Age, male gender, lateral collateral ligament repair, and dual-incision approach were not associated with increased ectopic bone formation. Distal humeral fractures were a significant predictor of heterotopic bone. In patients in whom HO ultimately developed, it was visible on radiographs obtained 2 weeks postoperatively in 86% of cases. This investigation found predictors for the development of HO after surgical fixation of intra-articular elbow fractures. Furthermore, HO went on to develop at the time of final follow-up in only 14% of patients without HO on radiographs obtained 2 weeks postoperatively. This may suggest that absence of HO on radiographs obtained 2 weeks postoperatively may predict a more favorable outcome. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  7. Early Detection of Burn Induced Heterotopic Ossification using Transcutaneous Raman Spectroscopy

    PubMed Central

    Peterson, Jonathan R.; Okagbare, Paul I.; De La Rosa, Sara; Cilwa, Katherine E.; Perosky, Joseph E.; Eboda, Oluwatobi N.; Donneys, Alexis; Su, Grace L.; Buchman, Steven R.; Cederna, Paul S.; Wang, Stewart C.; Kozloff, Kenneth M.; Morris, Michael D; Levi, Benjamin

    2013-01-01

    Introduction Heterotopic ossification (HO), or the abnormal formation of bone in soft tissue, occurs in over 60% of major burn injuries and blast traumas. A significant need exists to improve the current diagnostic modalities for HO which are inadequate to diagnose and intervene on HO at early time-points. Raman spectroscopy has been used in previous studies to report on changes in bone composition during bone development but has not yet been applied to burn induced HO. In this study, we validate transcutaneous, in-vivo Raman spectroscopy as a methodology for early diagnosis of HO in mice following a burn injury. Methods An Achilles tenotomy model was used to study HO formation. Following tenotomy, mice were divided into burn and sham groups with exposure of 30% surface area on the dorsum to 60° water or 30° water for 18 seconds respectively. In-vivo, transcutaneous Raman spectroscopy was performed at early time points (5 days, 2 and 3 weeks) and a late time point (3 months) on both the tenotomized and non-injured leg. These same samples were then dissected down to the bone and ex-vivo Raman measurements were performed on the excised tissue. Bone formation was verified with Micro CT and histology at corresponding time-points. Results Our Raman probe allowed non-invasive, transcutaneous evaluation of heterotopic bone formation. Raman data showed significantly increased bone mineral signaling in the tenotomy compared to control leg at 5 days post injury, with the difference increasing over time whereas Micro CT did not demonstrate heterotopic bone until three weeks. Ex-vivo Raman measurements showed significant differences in the amount of HO in the burn compared to sham groups and also showed differences in the spectra of new, ectopic bone compared to pre-existing cortical bone. Conclusions Burn injury increases the likelihood of developing HO when combined with traumatic injury. In our in-vivo mouse model, Raman spectroscopy allowed for detection of HO formation

  8. Symptomatic Heterotopic Ossification After Ulnar Collateral Ligament Reconstruction: Clinical Significance and Treatment Outcome.

    PubMed

    Andrachuk, John S; Scillia, Anthony J; Aune, Kyle T; Andrews, James R; Dugas, Jeffrey R; Cain, E Lyle

    2016-05-01

    Ulnar collateral ligament (UCL) reconstruction is an increasingly common procedure being performed in overhead throwing athletes. Recently, postoperative imaging has revealed the presence of heterotopic ossification (HO) in symptomatic patients. To determine the incidence of symptomatic HO after UCL reconstruction as well as the clinical outcomes after nonoperative or operative treatment of HO. Case series, Level of evidence, 4. A search was performed of diagnostic codes for all UCL reconstructions at a single institution between 2002 and 2012, and the charts were then reviewed of patients who returned to clinic for symptomatic HO after UCL reconstruction. All relevant clinical information, imaging findings, and return-to-play data were obtained. Eight patients were found to have developed symptomatic HO after UCL reconstruction. Of the 8 patients, 6 had gracilis tendon autograft at their primary surgery. All 8 patients had HO on the proximal end of their graft. Two patients were treated nonoperatively, and the remainder had excision of HO performed either arthroscopically or open. Six patients were able to return to the same or higher level of competition after treatment of HO. Symptomatic HO after UCL reconstruction is very uncommon but may prove to be a significant complication among athletes. With appropriate treatment, the majority of patients were able to return to the same level of play. Early identification of this complication is important, as revision surgery with excision of osteophytes resulted in a return to a similar level of play in most patients. © 2016 The Author(s).

  9. Characterization of Heterotopic Ossification Using Radiographic Imaging: Evidence for a Paradigm Shift

    PubMed Central

    Brownley, R. Cameron; Agarwal, Shailesh; Loder, Shawn; Eboda, Oluwatobi; Li, John; Peterson, Joshua; Hwang, Charles; Breuler, Christopher; Kaartinen, Vesa; Zhou, Bin; Mishina, Yuji; Levi, Benjamin

    2015-01-01

    Heterotopic ossification (HO) is the growth of extra-skeletal bone which occurs following trauma, burns, and in patients with genetic bone morphogenetic protein (BMP) receptor mutations. The clinical and laboratory evaluation of HO is dependent on radiographic imaging to identify and characterize these lesions. Here we show that despite its inadequacies, plain film radiography and single modality microCT continue to serve as a primary method of HO imaging in nearly 30% of published in vivo literature. Furthermore, we demonstrate that detailed microCT analysis is superior to plain film and single modality microCT radiography specifically in the evaluation of HO formed through three representative models due to its ability to 1) define structural relationships between growing extra-skeletal bone and normal, anatomic bone, 2) provide accurate quantification and growth rate based on volume of the space-occupying lesion, thereby facilitating assessments of therapeutic intervention, 3) identify HO at earlier times allowing for evaluation of early intervention, and 4) characterization of metrics of bone physiology including porosity, tissue mineral density, and cortical and trabecular volume. Examination of our trauma model using microCT demonstrated two separate areas of HO based on anatomic location and relationship with surrounding, normal bone structures. Additionally, microCT allows HO growth rate to be evaluated to characterize HO progression. Taken together, these data demonstrate the need for a paradigm shift in the evaluation of HO towards microCT as a standard tool for imaging. PMID:26544555

  10. RhoA mediates defective stem cell function and heterotopic ossification in dystrophic muscle of mice.

    PubMed

    Mu, Xiaodong; Usas, Arvydas; Tang, Ying; Lu, Aiping; Wang, Bing; Weiss, Kurt; Huard, Johnny

    2013-09-01

    Heterotopic ossification (HO) and fatty infiltration (FI) often occur in diseased skeletal muscle and have been previously described in various animal models of Duchenne muscular dystrophy (DMD); however, the pathological mechanisms remain largely unknown. Dystrophin-deficient mdx mice and dystrophin/utrophin double-knockout (dKO) mice are mouse models of DMD; however, mdx mice display a strong muscle regeneration capacity, while dKO mice exhibit a much more severe phenotype, which is similar to patients with DMD. Our results revealed that more extensive HO, but not FI, occurred in the skeletal muscle of dKO mice versus mdx mice, and RhoA activation specifically occurred at the sites of HO. Moreover, the gene expression of RhoA, BMPs, and several inflammatory factors were significantly up-regulated in muscle stem cells isolated from dKO mice; while inactivation of RhoA in the cells with RhoA/ROCK inhibitor Y-27632 led to reduced osteogenic potential and improved myogenic potential. Finally, inactivation of RhoA signaling in the dKO mice with Y-27632 improved muscle regeneration and reduced the expression of BMPs, inflammation, HO, and intramyocellular lipid accumulation in both skeletal and cardiac muscle. Our results revealed that RhoA represents a major molecular switch in the regulation of HO and muscle regeneration in dystrophic skeletal muscle of mice.

  11. Heterotopic ossification as an unusual complication after Guillain-Barré syndrome: a case report.

    PubMed

    Ryu, Su-Ra; Kim, Jae-Hyung; Choi, In-Sung; Han, Jae-Young; Lee, Sam-Gyu

    2008-03-01

    Heterotopic ossification (HO) is the abnormal development of bone within soft tissue. It is frequently encountered after traumatic brain injury or spinal cord injury, rather than lower motoneuron disease. It has been reported as a rare complication in Guillain-Barré syndrome (GBS). We present the case of a 31-year-old woman who suffered from pain and swelling with limitation of the passive range of motion on right hip joint, and who had been diagnosed with GBS about 1 year previously. She was wheelchair-bound and had incomplete tetraplegia with flaccidity. She was diagnosed as HO based on the radiologic imaging study. She did not reveal any encephalopathy-related symptoms or signs, and hypercalcemia, and/or related metabolic derangement during 1.5-year follow-up period. Owing to the paucity of other causative factors, we presumed that the long-time hypomobility, even though not accompanied by hypercalcemia, played a major role for the development of HO. Early active rehabilitative management was initiated. The outcome is not promising because of her long-standing paralyzed state; however, it was possible to prevent the aggravation of HO.

  12. The genetics of heterotopic ossification: insight into the bone remodeling pathway.

    PubMed

    Mitchell, Erika J; Canter, Jeffrey; Norris, Patrick; Jenkins, Judith; Morris, John

    2010-09-01

    Heterotopic Ossification (HO) is a significant complication after trauma occurring in 12% to 25% of fractures. Although clinical predictors have been studied to determine the likelihood of developing HO, the results have been inconsistent. This study examines genetic predictors of the HO phenotype to identify the "at-risk" patient and increase the understanding of the genetic contribution to the formation of HO. We examined the frequency of 61 single nucleotide polymorphisms (SNPs) in 1095 consecutive trauma patients with fractures. Radiographic studies of these patients were examined for HO in follow-up. Ten percent of the patients in the study demonstrated radiographic evidence of HO. Multivariate logistic regression was used to analyze each SNP independently while adjusting for severity of injury (as measured by the Trauma and Injury Severity Score). Three SNPs (beta2-adrenergic receptor, toll-like receptor 4, complement factor H) were identified that were associated with an increased or decreased frequency of HO. The less common polymorphism of the beta2-adrenergic receptor gene was associated with increased risk of HO. For toll-like receptor 4 and complement factor H, the less common polymorphism was associated with a decreased risk of HO. The SNPs identified as predictors of HO formation are representative of the adrenergic system, immune system, and the alternative complement system. This represents the interplay of multiple pathways that affect bone remodeling, aberrations of which may be found in the genome.

  13. Granting Immunity to FOP and Catching Heterotopic Ossification in the Act

    PubMed Central

    Kaplan, Frederick S.; Pignolo, Robert J.; Shore, Eileen M.

    2016-01-01

    The progressive transformation of one organ system into another is a fundamental signature of fibrodysplasia ossificans progressiva (FOP), the most catastrophic form of extraskeletal bone formation in humans. In all affected individuals, FOP is caused by heterozygous missense gain-of-function mutations in Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor. Loss of autoinhibition of the mutant receptor (mACVR1) results in dysregulated BMP pathway signaling, and is necessary for the myriad developmental features of FOP, but does not appear sufficient to induce the episodic flare-ups that lead to disabling post-natal heterotopic endochondral ossification (HEO) and that are a hallmark of the disease. Post-natal FOP flare-ups strongly implicate an underlying immunological trigger involving inflammation and the innate immune system. Recent studies implicate canonical and non-canonical TGFβ/BMP family ligands in the amplification of mACVR1 signaling leading to the formation of FOP lesions and resultant HEO. BMP and Activin ligands that stimulate mACVR1 signaling also have critical regulatory functions in the immune system. Cross-talk between the morphogenetic and immunological pathways that regulate tissue maintenance and wound healing identifies potential robust therapeutic targets for FOP. Here we review current evidence for an immunological trigger for flare-ups and HEO in FOP, propose a working schema for the pathophysiology of observed phenomena, and highlight outstanding questions under investigation. PMID:26706149

  14. Fetuin A is down-regulated in rats during heterotopic ossification after Achilles tenotomy.

    PubMed

    Wu, J; Xue, F; Shi, W Z; Xiao, H J

    2016-01-01

    We investigated the role of fetuin A during heterotopic ossification (HO) in rats following Achilles tenotomy. We performed a right midpoint Achilles tenotomy on 24 rats. At 5 and 10 h after surgery, we investigated the formation of ectopic bone using X-ray and histological examination. We evaluated the mRNA level of fetuin A using real-time PCR. Presence of fetuin A in the Achilles tendon was assessed by immunohistochemical staining. We also measured the serum concentration of fetuin A using enzyme linked immunosorbent assay (ELISA). The expression of fetuin A was significantly decreased in both the liver and Achilles tendon during HO. ELISA showed a small amount of fetuin A in blood throughout the development of HO. Immunohistochemical staining showed that fetuin A was abundant in the ectopic bone. Fetuin A appears to be involved in the formation of ectopic bone induced by Achilles tenotomy, and a deficiency of fetuin A plays a role in the development of HO.

  15. Rational design of cyclic peptides to disrupt TGF-Β/SMAD7 signaling in heterotopic ossification.

    PubMed

    Zhong, Biao; Zhang, Chi; Guo, Shang; Zhang, Changqing

    2017-03-01

    The human TGF-β/SMAD7 signaling has been recognized as an attractive target of heterotopic ossification (HO). Here, we report a successful rational design of cyclic peptides to disrupt the signaling pathway by targeting TGF-β-receptor complex. The intermolecular interaction between TGF-β and its cognate receptor is characterized in detail using molecular dynamics simulation, binding energetic analysis, and alanine scanning. With the computational analysis a binding loop of receptor protein is identified that plays an essential role in the peptide-mediated TGF-β-receptor interaction. Subsequently, the loop is stripped from the protein context to generate a linear peptide segment, which possesses considerable flexibility and intrinsic disorder, and thus would incur a large entropy penalty upon binding to TGF-β. In order to minimize the unfavorable entropic effect, the linear peptide is cyclized by adding a disulfide bond between the N- and C-terminal cysteine residues of the peptide, resulting in a cyclic peptide. In vitro fluorescence anisotropy assays substantiate that the cyclic peptide can bind tightly to TGF-β with determined Kd value of 54μM. We also demonstrated that structural optimization can further improve the peptide affinity by site-directed mutagenesis of selected residues based on the computationally modeled complex structure of TGF-β with the cyclic peptide.

  16. 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

  17. Fibrodysplasia Ossificans Progressiva-related Activated Activin-like Kinase Signaling Enhances Osteoclast Formation during Heterotopic Ossification in Muscle Tissues*

    PubMed Central

    Yano, Masato; Kawao, Naoyuki; Okumoto, Katsumi; Tamura, Yukinori; Okada, Kiyotaka; Kaji, Hiroshi

    2014-01-01

    Fibrodysplasia ossificans progressiva is characterized by extensive ossification within muscle tissues, and its molecular pathogenesis is responsible for the constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2). In this study, we investigated the effects of implanting ALK2 (R206H)-transfected myoblastic C2C12 cells into nude mice on osteoclast formation during heterotopic ossification in muscle and subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells with BMP-2 in nude mice induced robust heterotopic ossification with an increase in the formation of osteoclasts in muscle tissues but not in subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells in muscle induced heterotopic ossification more effectively than that of empty vector-transfected cells. A co-culture of ALK2 (R206H)-transfected C2C12 cells as well as the conditioned medium from ALK2 (R206H)-transfected C2C12 cells enhanced osteoclast formation in Raw264.7 cells more effectively than those with empty vector-transfected cells. The transfection of ALK2 (R206H) into C2C12 cells elevated the expression of transforming growth factor (TGF)-β, whereas the inhibition of TGF-β signaling suppressed the enhanced formation of osteoclasts in the co-culture with ALK2 (R206H)-transfected C2C12 cells and their conditioned medium. In conclusion, this study demonstrated that the causal mutation transfection of fibrodysplasia ossificans progressiva in myoblasts enhanced the formation of osteoclasts from its precursor through TGF-β in muscle tissues. PMID:24798338

  18. The development of a rat model to investigate the formation of blast-related post-traumatic heterotopic ossification.

    PubMed

    Polfer, E M; Hope, D N; Elster, E A; Qureshi, A T; Davis, T A; Golden, D; Potter, B K; Forsberg, J A

    2015-04-01

    Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification. ©2015 The British Editorial Society of Bone & Joint Surgery.

  19. Heterotopic Ossification around the Knee after Internal Fixation of a Complex Tibial Plateau Fracture Combined with the Use of Demineralized Bone Matrix (DBM): A Case Report

    PubMed Central

    Nota, Sjoerd P.F.T.; Kloen, Peter

    2014-01-01

    Demineralized bone matrix has been successfully commercialized as an alternative bone graft material that not only can function as filler but also as an osteoinductive graft. Numerous studies have confirmed its beneficial use in clinical practice. Heterotopic ossification after internal fixation combined with the use of demineralized bone matrix has not been widely reported. In this paper we describe a 39 year old male who sustained a complex articular fracture that developed clinically significant heterotopic ossification after internal fixation with added demineralized bone matrix. Although we cannot be sure that there is a cause-and-effect relation between demineralized bone matrix and the excessive heterotopic ossification seen in our patient, it seems that some caution in using demineralised bone matrix in similar cases is warranted. Also, given the known inter- and intraproduct variability, the risks and benefits of these products should be carefully weighed. PMID:25692153

  20. Cost of Radiotherapy Versus NSAID Administration for Prevention of Heterotopic Ossification After Total Hip Arthroplasty

    SciTech Connect

    Strauss, Jonathan B. Chen, Sea S.; Shah, Anand P.; Coon, Alan B.; Dickler, Adam

    2008-08-01

    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 surgery 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.

  1. Association between alendronate, serum alkaline phosphatase level, and heterotopic ossification in individuals with spinal cord injury

    PubMed Central

    Ploumis, Avraam; Donovan, Jayne M.; Olurinde, Mobolaji O.; Clark, Dana M.; Wu, Jason C.; Sohn, Douglas J.; O'Connor, Kevin C.

    2015-01-01

    Context/objective Only sparse evidence exists regarding the effectiveness of oral alendronate (ALN) in the prevention of heterotopic ossification (HO) in patients with spinal cord injury (SCI). The objective of this study is to investigate the protective effect of oral ALN intake on the appearance of HO in patients with SCI. Study design Retrospective database review. Setting A Spinal Cord Unit at a Rehabilitation Hospital. Participants Two hundred and ninety-nine patients with SCI during acute inpatient rehabilitation. Interventions Administration of oral ALN. Outcome measures The incidence of HO during rehabilitation was compared between patients with SCI receiving oral ALN (n = 125) and patients with SCI not receiving oral ALN (n = 174). The association between HO and/or ALN intake with HO risk factors and biochemical markers of bone metabolism were also explored. Results HO developed in 19 male patients (6.35%), however there was no significant difference in the incidence of HO in patients receiving oral ALN or not. The mean odds ratio of not developing versus developing HO given ALN exposure was 0.8. Significant correlation was found between abnormal serum alkaline phosphatase (ALP) levels and HO appearance (P < 0.001) as well as normal serum ALP and ALN intake (P < 0.05). Conclusion Even though there was no direct prevention of HO in patients with SCI by oral ALN intake, abnormal serum ALP was found more frequently in patients with HO development and without oral ALN intake. This evidence could suggest that ALN may play a role in preventing HO, especially in patients with acute SCI with increasing levels of serum ALP. PMID:24820653

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

    SciTech Connect

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

    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 develop 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.

  3. 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

  4. Multilevel arthroplasty for cervical spondylosis: more heterotopic ossification at 3 years of follow-up.

    PubMed

    Wu, Jau-Ching; Huang, Wen-Cheng; Tsai, Tzu-Yun; Fay, Li-Yu; Ko, Chin-Chu; Tu, Tsung-Hsi; Wu, Ching-Lan; Cheng, Henrich

    2012-09-15

    Retrospective cohort study. To investigate the differences between single- and multilevel degenerative disc diseases (DDDs) treated with cervical arthroplasty. The US Food and Drug Administration clinical trials compared arthroplasty with anterior cervical discectomy and fusion for single-level DDD. However, cervical arthroplasty for multilevel DDD is rarely addressed in the literature. A total of 102 consecutive patients who underwent Bryan arthroplasty were divided into either a single- or multilevel group. Clinical outcomes were measured by the visual analogue scale (VAS) of neck and arm, and by the neck disability index with a minimum follow-up of 25 months. Every patient had radiographical evaluations, and computed tomography. Eighty-six patients (84.3%) completed the follow-up with a mean time of 38.3 ± 8.7 months. Postoperatively, there were significant improvements in clinical outcomes (i.e., VAS neck, VAS arm, and neck disability index) at each time point of evaluation (i.e., 3-, 6-, 12-, and 24 mo postoperation). The sex composition and clinical outcome improvements between the single- and multilevel groups were not significantly different. The multilevel group was older (51.3 ± 8.6 vs. 46.3 ± 11.2 yr; P = 0.02), had more intraoperative blood loss (218.0 ± 182.4 vs. 102.8 ± 79.2 mL; P = 0.001), and demonstrated a higher rate of heterotopic ossification (HO) than the single-level group (66.0% vs. 25.0%; P < 0.001). The majority (97.7%) of the artificial discs in this series remained mobile despite HO. Clinical outcomes of cervical arthroplasty in multilevel spondylosis are similar to single-level outcomes. However, the significantly higher rate of HO found in multilevel arthroplasty and its long-term effect warrant further investigation.

  5. Postoperative Single-Fraction Radiation for Prevention of Heterotopic Ossification of the Elbow

    SciTech Connect

    Robinson, Clifford G.; Polster, Joshua M.; Reddy, Chandana A.; Lyons, Janice A.; Evans, Peter J.; Lawton, Jeffrey N.; Graham, Thomas J.; Suh, John H.

    2010-08-01

    Purpose: Heterotopic ossification (HO) about the elbow has been described after surgery, trauma, and burns. Even limited deposits can lead to significant functional deficits. Little data exist regarding outcomes of patients treated with radiation therapy (RT) after elbow surgery. We report here the Cleveland Clinic experience with single-fraction radiation following surgery to the elbow. The primary endpoint was the rate of new HO after RT. Secondary endpoints were range of motion, functional compromise, and toxicity. Methods and Materials: From May 1993 to July 2006, 36 patients underwent elbow surgery followed by single-fraction RT. Range of motion data were collected before and during surgery and at last follow-up. Radiographs were reviewed for persistent or new HO. Patient and treatment factors were analyzed for correlation with development of HO or functional compromise. Results: Median follow-up was 8.7 months, median age was 42 years, and 75% of patients were male. Twenty-six (72%) patients had HO prior to surgery. All patients had significant limitations in flexion/extension or pronation/supination at baseline. Thirty-one (86%) patients had prior elbow trauma, and 26 (72%) patients had prior surgery. RT was administered a median of 1 day postoperatively (range, 1-4 days). Thirty-four patients received 700 cGy, and 2 patients received 600 cGy. Three (8%) patients developed new HO after RT. All patients had improvement in range of motion from baseline. No patient or treatment factors were significantly associated with the development of HO or functional compromise. Conclusions: Single-fraction RT after surgery to the elbow is associated with favorable functional and radiographic outcomes.

  6. Prophylactic radiotherapy against heterotopic ossification following internal fixation of acetabular fractures: a comparative estimate of risk

    PubMed Central

    Nasr, P; Yip, G; Scaife, J E; House, T; Thomas, S J; Harris, F; Owen, P J; Hull, P

    2014-01-01

    Objective: Radiotherapy (RT) is effective in preventing heterotopic ossification (HO) around acetabular fractures requiring surgical reconstruction. We audited outcomes and estimated risks from RT prophylaxis, and alternatives of indometacin or no prophylaxis. Methods: 34 patients underwent reconstruction of acetabular fractures through a posterior approach, followed by a 8-Gy single fraction. The mean age was 44 years. The mean time from surgery to RT was 1.1 days. The major RT risk is radiation-induced fatal cancer. The International Commission on Radiological Protection (ICRP) method was used to estimate risk, and compared with a method (Trott and Kemprad) specifically for estimating RT risk for benign disease. These were compared with risks associated with indometacin and no prophylaxis. Results: 28 patients (82%) developed no HO; 6 developed Brooker Class I; and none developed Class II–IV HO. The ICRP method suggests a risk of fatal cancer in the range of 1 in 1000 to 1 in 10,000; the Trott and Kemprad method suggests 1 in 3000. For younger patients, this may rise to 1 in 2000; and for elderly patients, it may fall to 1 in 6000. The risk of death from gastric bleeding or perforation from indometacin is 1 in 180 to 1 in 900 in older patients. Without prophylaxis risk of death from reoperation to remove HO is 1 in 4000 to 1 in 30,000. Conclusion: These results are encouraging, consistent with much larger series and endorse our multidisciplinary management. Risk estimates can be used in discussion with patients. Advances in knowledge: The risk from RT prophylaxis is small, it is safer than indometacin and substantially overlaps with the range for no prophylaxis. PMID:25089852

  7. miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

    PubMed Central

    Tu, Bing; Liu, Shen; Yu, Bo; Zhu, Jing; Ruan, Hongjiang; Tang, Tingting; Fan, Cunyi

    2016-01-01

    Emerging evidence has indicated that dysregulated microRNAs (miRNAs) have an important role in bone formation. However, the pathophysiological role of miRNAs in traumatic heterotopic ossification (HO) remains to be elucidated. Using gene expression profile analyses and subsequent confirmation with real-time PCR assays, we identified the decreased expression of miRNA-203 (miR-203) and increased expression of Runx2 as responses to the development of traumatic HO. We found that miR-203 expression was markedly higher in primary and recurrent HO tissues than in normal bones. The upregulation of miR-203 significantly decreased the level of Runx2 expression, whereas miR-203 downregulation increased Runx2 expression. Mutation of the putative miR-203-binding sites in Runx2 mRNA abolished miR-203-mediated repression of Runx2 3'-untranslated region luciferase reporter activity, indicating that Runx2 is an important target of miR-203 in osteoblasts. We also found that miR-203 is negatively correlated with osteoblast differentiation. Furthermore, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-203 and decreased by agomir-203. We showed that miR-203 suppresses osteoblast activity by inhibiting the β-catenin and extracellular signal-regulated kinase pathways. Moreover, using a tenotomy mouse HO model, we found an inhibitory role of miR-203 in regulating HO in vivo; pretreatment with antagomiR-203 increased the development of HO. These data suggest that miR-203 has a crucial role in suppressing HO by directly targeting Runx2 and that the therapeutic overexpression of miR-203 may be a potential strategy for treating traumatic HO. PMID:27787524

  8. Heterotopic Ossification Prophylaxis After Total Hip Arthroplasty: Randomized Trial of 400 vs 700 cGy.

    PubMed

    Liu, Jane Z; Frisch, Nicholas B; Barden, Regina M; Rosenberg, Aaron G; Silverton, Craig D; Galante, Jorge O

    2017-04-01

    Heterotopic ossification (HO) is a known complication following total hip arthroplasty. Radiation is an effective prophylaxis, but an optimal protocol has yet to be determined. We performed a randomized, double-blinded clinical trial in high-risk patients to determine the efficacy of 400 vs 700 cGy doses of radiation. One hundred forty-seven patients undergoing total hip arthroplasty and at high risk for HO at an urban medical center were randomized to receive either a single 400 or 700 cGy dose of radiation postoperatively. High risk was defined as a diagnosis of diffuse idiopathic skeletal hyperostosis, hypertrophic osteoarthritis, ankylosing spondylitis, or history of previous HO. Radiation was administered on the first or second postoperative day. A single blinded reviewer graded radiographs taken immediately postoperatively and at a minimum of 6 months postoperatively using the Brooker classification. Progression was defined as an increase in Brooker classification. Operative data including surgical approach, implant fixation, revision surgery, and postoperative range of motion data were also collected. A significantly greater portion of patients who received the 400 cGy dose demonstrated progression of HO than patients who received the 700 cGy dose. There were no wound complications. No preoperative factors were associated with a higher rate of progression. Patients who progressed had less flexion on physical examination than patients who did not progress, but this was not clinically significant. Seven hundred centigray was superior to 400 cGy in preventing HO formation following total hip arthroplasty in high-risk patients and may be the more effective treatment in this population. Further studies comparing 700 cGy to dosages between 400 and 700 cGy may help to clarify if a more optimal dose can be identified. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Clinically relevant heterotopic ossification after elbow fracture surgery: a risk factors study.

    PubMed

    Hong, C C; Nashi, N; Hey, H W; Chee, Y H; Murphy, D

    2015-04-01

    Heterotopic ossification (HO) is a common complication of elbow fracture surgery that can significantly impair function and range of motion (ROM). Whereas numerous studies have assessed HO after hip trauma or replacement surgery, few data have been reported on the prevalence and risk factors of HO after elbow fractures. Our objective was to investigate the prevalence and risk factors of clinically relevant HO after elbow fracture surgery under the hypothesis that the ability to identify high-risk patients would improve treatment tailoring and assist in meeting patient expectations. We retrospectively included consecutive patients who had surgery for elbow injuries between January 2007 and December 2011. Patient demographics, operative details, and radiographs were reviewed. Of 124 elbows in 122 patients, 38 (30.6%) had HO and 26 (21%) clinically relevant HO. The prevalence of clinically relevant HO was highest in floating elbow injury, followed by combined olecranon and radial head fractures, types A and B distal humerus fractures, and terrible triad injury. By multiple logistic regression, factors that independently predicted clinically relevant HO were fracture-dislocation (OR, 4.87; 95%CI, 1.78-13.29; P=0.002) and longer time to surgery (P<0.05). Of the 26 patients with clinically relevant HO, 6 (23%) eventually required revision elbow surgery to improve ROM. HO of the elbow occurred in almost one-third of our patients with surgically treated elbow fractures. Fracture-dislocation of the elbow and longer time to surgery independently predicted HO responsible for ROM loss. Clinically relevant HO was associated with significant morbidity. Level IV, retrospective study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Heterotopic Ossification following acetabular fixation: Incidence and risk factors: 10-year experience of a tertiary centre.

    PubMed

    Elhassan, Yahya; Abdelhaq, Ady; Piggott, Robert P; Osman, Mugtaba; McElwain, John P; Leonard, Mike

    2016-06-01

    Heterotopic Ossification (HO) is a well-recognized complication following acetabular fracture fixation and its presence is prognostic for suboptimal clinical outcome. There are many controversies pertaining to its aetiology, including surgical approach, associated injuries and the use of HO prophylaxis. Long term data from high volume centres is necessary to address these issues. To determine the incidence of HO post open reduction and internal fixation (ORIF) of acetabular fractures and to examine the associated risk and prognostic factors. We studied a cohort of 369 consecutive acetabular fractures that underwent ORIF at our institution over a 10 year period. Data was analyzed using univariate and multivariate logistic regression. The existence of HO was evident in 65 patients (17.62%), of these 39 (60.0%) were Class I, 16 (24.6%) were Class II, 8 (12.3%) were Class III, and 2 (3.1%) were Class IV according to Brooker Classification. We found a significant association between admission to an Intensive Care Unit (ICU) (P-value=0.039), chest injury (P-value=0.013), multiple fractures (P-value=0.005), and the time lapse between injury and operation (P-value=0.025), and some statistical significance with surgical approach, ipsilateral fractures, open fractures, tibial and patellar fractures. Age over 30 years as the only prognostic factor for severe HO. Prophylaxis with Indomethacin did not appear to confer any benefit in our patient group. The risk factors for developing HO following acetabular fracture fixation are multifactorial and include admission to ICU, associated chest injuries, multiple fractures and delay between injury and surgery. Surgical approach, ipsilateral fractures and tibia and patellar fractures may also play a role. Age over thirty years was the only prognostic factor for developing severe HO. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Heterotopic ossification as rare complication of hemiplegia following stroke: two cases.

    PubMed

    Gurcay, Eda; Ozturk, Erhan Arif; Erdem, Tuba; Gurcay, Ahmet Gurhan; Cakci, Aytul

    2013-01-01

    Heterotopic ossification (HO), characterized by new bone formation in the periarticular regions of large joints, is frequently seen after spinal cord injury, traumatic brain injury, burn and trauma. It is a rare complication of hemiplegia following stroke, with a reported incidence of 1% or less. This study reports two unusual presentations of HO: (1) A 56-year-old male with a history of atrial fibrillation on warfarin developed sudden-onset left hemiplegia. Eight months after the event, he was diagnosed with HO of the hip joint including both the affected and unaffected sides. (2) A 55-year-old female with left hemiplegia due to subarachnoid bleeding developed HO on the left hip joint 7 months later. In both cases, spasticity around the hip muscle groups, especially hip flexors, adductors and knee extensors, and limited range of motion accompanied by pain were present. X-ray and pelvic computed tomography revealed HO around the hip joints. After 4 weeks of inpatient rehabilitation, the ranges of hip joint motion improved, without exceeding 10° in the direction of flexion and rotations, and ambulation levels were wheelchair-bound for the first case and dependent on a cane for the second case. Considering the presented cases, it is suggested that HO should be kept in mind in the differential diagnosis in stroke patients presenting with spontaneous joint pain or limitation. The clinical importance of HO development on both the affected and unaffected sides in post-stroke hemiplegia is emphasized, since it may worsen the patient's functional status.

  12. Preoperative irradiation for the prevention of heterotopic ossification induces local inflammation in humans.

    PubMed

    Hoff, Paula; Rakow, Anastasia; Gaber, Timo; Hahne, Martin; Sentürk, Ufuk; Strehl, Cindy; Fangradt, Monique; Schmidt-Bleek, Katharina; Huscher, Dörte; Winkler, Tobias; Matziolis, Dörte; Matziolis, Georg; Badakhshi, Harun; Burmester, Gerd-Rüdiger; Duda, Georg N; Perka, Carsten; Buttgereit, Frank

    2013-07-01

    Radiation of the hip is an established method to prevent heterotopic ossification (HO) following total hip arthroplasty (THA) but the precise mechanism is unclear. As inflammatory processes are suggested to be involved in the pathogenesis of HO, we hypothesized that the preoperative irradiation impacts local immune components. Therefore, we quantified immune cell populations and cytokines in hematomas resulting from the transection of the femur in two groups of patients receiving THA: patients irradiated preoperatively (THA-X-hematoma: THA-X-H group) in the hip region (7 Gy) in order to prevent HO and patients who were not irradiated (THA-H group) but were postoperatively treated with non-steroidal anti-inflammatory drugs (NSAIDs). Radiation resulted in significantly increased frequencies of T cells, cytotoxic T cells, NKT cells and CD25+CD127- Treg cells, whereas the number of naive CD45RA-expressing cytotoxic T cells was reduced. These results indicate differential immune cell activation, corroborated by our findings of significantly higher concentrations of pro-inflammatory cytokines (e.g., IL-6, IFNγ) and chemokines (e.g., MCP-1, RANTES) in the THA-X-H group as compared to THA-H group. In contrast, the concentration of the angiogenic VEGF was significantly suppressed in the THA-X-H group. We conclude that preoperative irradiation results in significant changes in immune cell composition and cytokine secretion in THA-hematomas, establishing a specific - rather proinflammatory - milieu. This increase of inflammatory activity together with the observed suppression in VEGF secretion may contribute to the prevention of HO.

  13. 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

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

    PubMed

    Zotz, T G G; Paula, J B de

    2015-11-01

    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.

  15. Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty

    PubMed Central

    2010-01-01

    Background Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress. Results The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species. Conclusions Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA. PMID:20809936

  16. Heterotopic ossification in the submental triangle remote from the vascular pedicle after reconstruction with a fibular free flap: a previously unreported complication.

    PubMed

    Panaretou, E; Blythe, J N St J; Conti, M; Brennan, P A

    2016-05-01

    Fibular free flaps are routinely used to reconstruct segmental mandibular defects after resection. While ossification of the vascular pedicle is uncommon but well reported, to our knowledge, heterotopic ossification remote from the pedicle has not previously been described. We report a case in which this occurred. It serves as a reminder that bony, hard lumps in the neck can present years after reconstruction with a fibular flap.

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

    SciTech Connect

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

    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 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.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 by the

  18. Risk factors for the development of heterotopic ossification after acetabular fracture fixation.

    PubMed

    Firoozabadi, Reza; O'Mara, Timothy J; Swenson, Alan; Agel, Julie; Beck, John D; Routt, Milton

    2014-11-01

    Heterotopic ossification (HO) is a common complication of the operative treatment of acetabular fractures. Although the surgical approach has been shown to correlate with the development of ectopic bone, specific risk factors have not been elucidated. The purposes of this study were to determine specific risk factors associated with the development of severe HO and the frequency with which patients develop severe HO after acetabular fracture fixation through an isolated Kocher-Langenbeck approach. Using an institutional orthopaedic trauma database at a regional Level I trauma center, patients undergoing open treatment of acetabular fractures during the study period (January 2000 to January 2010) were identified. A review of medical records and imaging studies was performed on 508 patients who were treated by the senior author (MR) through an isolated Kocher-Langenbeck approach. During the study period, the senior author used indomethacin for HO prophylaxis in patients who had ipsilateral femur fracture treated with antegrade reamed medullary nailing or severe local soft tissue injury; 49 (10%) of the patients he treated with the Kocher-Langenbeck approach received prophylaxis, and they were excluded from this study, leaving a total of 459 patients who met inclusion criteria. Of those, 147 (29%) were lost to followup or did not have radiographs both before and at a minimum of 6 weeks (median, 1 week; range, 0-3 weeks), leaving 312 (61% of the patients treated with the Kocher-Langenbeck approach during this time) available for this analysis. Demographic data as well as information related to cause of injury, associated periacetabular findings, other system injuries, and treatment were gathered. Final followup radiographs were assessed for the presence of ectopic bone by two of the authors (TJO, AS) using the modified Brooker classification. Logistic regression was performed to identify possible predictors of development of severe ectopic bone. The only predictor we

  19. Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification

    PubMed Central

    Davis, Eleanor L.; Salisbury, Elizabeth A.; Olmsted‐Davis, Elizabeth

    2015-01-01

    ABSTRACT Heterotopic ossification (HO) is the de novo formation of bone that occurs in soft tissue, through recruitment, expansion, and differentiation of multiple cells types including transient brown adipocytes, osteoblasts, chondrocytes, mast cells, and platelets to name a few. Much evidence is accumulating that suggests changes in metabolism may be required to accomplish this bone formation. Recent work using a mouse model of heterotopic bone formation reliant on delivery of adenovirus‐transduced cells expressing low levels of BMP2 showed the immediate expansion of a unique brown adipocyte‐like cell. These cells are undergoing robust uncoupled oxidative phosphorylation to a level such that oxygen in the microenvironment is dramatically lowered creating areas of hypoxia. It is unclear how these oxygen changes ultimately affect metabolism and bone formation. To identify the processes and changes occurring over the course of bone formation, HO was established in the mice, and tissues isolated at early and late times were subjected to a global metabolomic screen. Results show that there are significant changes in both glucose levels, as well as TCA cycle intermediates. Additionally, metabolites necessary for oxidation of stored lipids were also found to be significantly elevated. The complete results of this screen are presented here, and provide a unique picture of the metabolic changes occurring during heterotopic bone formation. J. Cell. Biochem. 117: 1044–1053, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. PMID:26627193

  20. Surgical Excision of Heterotopic Ossification Leads to Re-Emergence of Mesenchymal Stem Cell Populations Responsible for Recurrence.

    PubMed

    Agarwal, Shailesh; Loder, Shawn; Cholok, David; Li, John; Breuler, Chris; Drake, James; Brownley, Cameron; Peterson, Joshua; Li, Shuli; Levi, Benjamin

    2017-03-01

    Trauma-induced heterotopic ossification (HO) occurs after severe musculoskeletal injuries and burns, and presents a significant barrier to patient rehabilitation. Interestingly, the incidence of HO significantly increases with repeated operations and after resection of previous HO. Treatment of established heterotopic ossification is challenging because surgical excision is often incomplete, with evidence of persistent heterotopic bone. As a result, patients may continue to report the signs or symptoms of HO, including chronic pain, nonhealing wounds, and joint restriction. In this study, we designed a model of recurrent HO that occurs after surgical excision of mature HO in a mouse model of hind-limb Achilles' tendon transection with dorsal burn injury. We first demonstrated that key signaling mediators of HO, including bone morphogenetic protein signaling, are diminished in mature bone. However, upon surgical excision, we have noted upregulation of downstream mediators of osteogenic differentiation, including pSMAD 1/5. Additionally, surgical excision resulted in re-emergence of a mesenchymal cell population marked by expression of platelet-derived growth factor receptor-α (PDGFRα) and present in the initial developing HO lesion but absent in mature HO. In the recurrent lesion, these PDGFRα+ mesenchymal cells are also highly proliferative, similar to the initial developing HO lesion. These findings indicate that surgical excision of HO results in recurrence through similar mesenchymal cell populations and signaling mechanisms that are present in the initial developing HO lesion. These results are consistent with findings in patients that new foci of ectopic bone can develop in excision sites and are likely related to de novo formation rather than extension of unresected bone. Stem Cells Translational Medicine 2017;6:799-806.

  1. Surgical Excision of Heterotopic Ossification Leads to Re-Emergence of Mesenchymal Stem Cell Populations Responsible for Recurrence.

    PubMed

    Agarwal, Shailesh; Loder, Shawn; Cholok, David; Li, John; Breuler, Chris; Drake, James; Brownley, Cameron; Peterson, Joshua; Li, Shuli; Levi, Benjamin

    2016-10-05

    : Trauma-induced heterotopic ossification (HO) occurs after severe musculoskeletal injuries and burns, and presents a significant barrier to patient rehabilitation. Interestingly, the incidence of HO significantly increases with repeated operations and after resection of previous HO. Treatment of established heterotopic ossification is challenging because surgical excision is often incomplete, with evidence of persistent heterotopic bone. As a result, patients may continue to report the signs or symptoms of HO, including chronic pain, nonhealing wounds, and joint restriction. In this study, we designed a model of recurrent HO that occurs after surgical excision of mature HO in a mouse model of hind-limb Achilles' tendon transection with dorsal burn injury. We first demonstrated that key signaling mediators of HO, including bone morphogenetic protein signaling, are diminished in mature bone. However, upon surgical excision, we have noted upregulation of downstream mediators of osteogenic differentiation, including pSMAD 1/5. Additionally, surgical excision resulted in re-emergence of a mesenchymal cell population marked by expression of platelet-derived growth factor receptor-α (PDGFRα) and present in the initial developing HO lesion but absent in mature HO. In the recurrent lesion, these PDGFRα+ mesenchymal cells are also highly proliferative, similar to the initial developing HO lesion. These findings indicate that surgical excision of HO results in recurrence through similar mesenchymal cell populations and signaling mechanisms that are present in the initial developing HO lesion. These results are consistent with findings in patients that new foci of ectopic bone can develop in excision sites and are likely related to de novo formation rather than extension of unresected bone.

  2. Editorial Commentary: The Efficacy of Nonsteroidal Anti-inflammatory Drugs for Prophylaxis of Heterotopic Ossification in Hip Arthroscopy--Do We Treat Patients or X-rays?

    PubMed

    Miller, G Klaud

    2016-03-01

    A systematic review of 5 series comparing the incidence of heterotopic ossification after hip arthroscopy with and without nonsteroidal anti-inflammatory drug prophylaxis showed a statistically significant improvement with the use of prophylaxis. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  3. Preventing Heterotopic Ossification in Combat Casualties-Which Models Are Best Suited for Clinical Use?

    PubMed

    Alfieri, Keith A; Potter, Benjamin K; Davis, Thomas A; Wagner, Matthew B; Elster, Eric A; Forsberg, Jonathan A

    2015-09-01

    To prevent symptomatic heterotopic ossification (HO) and guide primary prophylaxis in patients with combat wounds, physicians require risk stratification methods that can be used early in the postinjury period. There are no validated models to help guide clinicians in the treatment for this common and potentially disabling condition. We developed three prognostic models designed to estimate the likelihood of wound-specific HO formation and compared them using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) to determine (1) which model is most accurate; and (2) which technique is best suited for clinical use. We obtained muscle biopsies from 87 combat wounds during the first débridement in the United States, all of which were evaluated radiographically for development of HO at a minimum of 2 months postinjury. The criterion for determining the presence of HO was the ability to see radiographic evidence of ectopic bone formation within the zone of injury. We then quantified relative gene expression from 190 wound healing, osteogenic, and vascular genes. Using these data, we developed an Artificial Neural Network, Random Forest, and a Least Absolute Shrinkage and Selection Operator (LASSO) Logistic Regression model designed to estimate the likelihood of eventual wound-specific HO formation. HO was defined as any HO visible on the plain film within the zone of injury. We compared the models accuracy using area under the ROC curve (area under the curve [AUC]) as well as DCA to determine which model, if any, was better suited for clinical use. In general, the AUC compares models based solely on accuracy, whereas DCA compares their clinical utility after weighing the consequences of under- or overtreatment of a particular disorder. Both the Artificial Neural Network and the LASSO logistic regression models were relatively accurate with AUCs of 0.78 (95% confidence interval [CI], 0.72-0.83) and 0.75 (95% CI, 0

  4. 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

  5. Extracorporeal Shock Wave Therapy for Painful Chronic Neurogenic Heterotopic Ossification After Traumatic Brain Injury: A Case Report

    PubMed Central

    Choi, Yong Min; Hong, Seok Hyun; Lee, Chang Hyun; Kang, Jin Ho

    2015-01-01

    Neurogenic heterotopic ossification (NHO) is a process of benign bone formation and growth in soft tissues surrounding major synovial joints and is associated with central nervous system (CNS) injuries. It is a common complication in major CNS injuries, such as traumatic brain injury, spinal cord injury, and stroke. Here, we report the case of a 72-year-old male, who experienced a traumatic brain injury and painful chronic NHO around the left hip joint. Three applications of extracorporeal shock wave therapy (ESWT) were administered to the area of NHO, which resulted in pain relief and an improvement in the loss of motion in the left hip joint. Improvements were also noted in walking performance and activities of daily living, although the size of NHO remained unchanged. Therapeutic effects of ESWT lasted for 12 weeks. PMID:25932431

  6. Acceptable outcome following resection of bilateral large popliteal space heterotopic ossification masses in a spinal cord injured patient: a case report.

    PubMed

    Espandar, Ramin; Haghpanah, Babak

    2010-06-22

    Spinal cord injury is a well-known predisposing factor for development of heterotopic ossification around the joints especially hip and elbow. Heterotopic ossification about the knee is usually located medially, laterally or anteriorly; besides, the knee is generally fixed in flexion. There are only a few reports of heterotopic bone formation at the posterior aspect of the knee (popliteal space) and fixation of both knees in extension; so, there is little experience in operative management of such a problem.Here, we present a 39-years old paraplegic man who was referred to us five years after trauma with a request of above knee amputation due to sever impairment of his life style and adaptive capacity for daily living because of difficulties in using wheelchair. The principle reason for the impairment was fixed full extension of both knees as the result of bilateral large heterotopic ossification masses in popliteal fossae. The bony masses were surgically resected with acceptable outcome. The anatomic position of the ossified masses as well as ankylosis of both knees in full extension, and the acceptable functional outcome of surgery which was done after a long period of five years following injury makes this case unique.

  7. Acceptable outcome following resection of bilateral large popliteal space heterotopic ossification masses in a spinal cord injured patient: a case report

    PubMed Central

    2010-01-01

    Spinal cord injury is a well-known predisposing factor for development of heterotopic ossification around the joints especially hip and elbow. Heterotopic ossification about the knee is usually located medially, laterally or anteriorly; besides, the knee is generally fixed in flexion. There are only a few reports of heterotopic bone formation at the posterior aspect of the knee (popliteal space) and fixation of both knees in extension; so, there is little experience in operative management of such a problem. Here, we present a 39-years old paraplegic man who was referred to us five years after trauma with a request of above knee amputation due to sever impairment of his life style and adaptive capacity for daily living because of difficulties in using wheelchair. The principle reason for the impairment was fixed full extension of both knees as the result of bilateral large heterotopic ossification masses in popliteal fossae. The bony masses were surgically resected with acceptable outcome. The anatomic position of the ossified masses as well as ankylosis of both knees in full extension, and the acceptable functional outcome of surgery which was done after a long period of five years following injury makes this case unique. PMID:20569483

  8. Comparative clinical study of the prophylaxis of heterotopic ossifications after total hip arthroplasty using etoricoxib or diclofenac.

    PubMed

    Winkler, Sebastian; Springorum, Hans-Robert; Vaitl, Tobias; Handel, Martin; Barta, Sabine; Kehl, Victoria; Craiovan, Benjamin; Grifka, Joachim

    2016-04-01

    This study investigated whether etoricoxib (COX-II blocker) has a superior efficacy of preventing heterotopic ossification (HO) after total hip arthroplasty (THA) compared to diclofenac (non-selective NSAID). One hundred patients were included (50 in each group) in this single centre, prospective, double-blinded, randomized, controlled trial. Etoricoxib (90 mg) was administered once and diclofenac (75 mg) twice per day for a perioperative period of nine days. The incidence of HO was evaluated on radiographs of the pelvis six months after surgery. Eighty nine of 100 (89 %) patients could be analysed. The overall HO incidence was 37.8 %. There was no significant difference between both study groups. Twelve patients (27.3 %) of the DIC group and 13 patients (28.9 %) of the ETO group showed Brooker grade I ossifications. Five patients (11.4 %) of the DIC and four patients of the ETO (8.9 %) group showed grade II HO formations. No class III or IV HO formations occured in both groups. Ad hoc analysis detected a negative correlation between HO incidence and limited abduction and internal rotation of the hip. Etoricoxib and diclofenac are equally effective for oral HO prophylaxis after primary cementless THA when given for nine peri-operative days to ensure a full recovery and high patient satisfaction.

  9. Comparison of Development of Heterotopic Ossification in Injured US and UK Armed Services Personnel with Combat-Related Amputations: Preliminary Findings and Hypotheses Regarding Causality

    DTIC Science & Technology

    2010-07-01

    be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of...SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 7 19a. NAME OF RESPONSIBLE PERSON a REPORT unclassified b...ossification. Paraplegia . 1992;30:165–168. 17. Ebinger T, Roesch M, Kiefer H, Kinzl L, Schulte M. Influence of etiology in heterotopic bone formation

  10. Double-level cervical total disc replacement for adjacent segment disease: is it a useful treatment? Description of late onset heterotopic ossification and review of the literature.

    PubMed

    Barbagallo, G M V; Certo, F; Visocchi, M; Sciacca, G; Albanese, V

    2014-01-01

    We report a rare case of double-level adjacent segment disease (ASD), occurring ten years later an anterior cervical discectomy (ACD) without fusion, treated by cervical arthroplasty, highlighting the outcome at long-term follow-up and focusing on heterotopic ossification. In 1995 a 25-year-old man satisfactorily underwent ACD at C4/C5. At that time MRI also showed signs of degenerative disc disease (DDD) at C3/C4 and C5/C6. Ten years later, a new MRI scan showed a large C3/C4 and a smaller C5/C6 soft disc hernia together with spondylotic changes at the level above and below the site of the first surgery. At C4/C5 imaging revealed a kyphotic stable "pseudoarthrosis" with anterior bridging osteophyte. The patient underwent double-level arthroplasty with ProDisc-C. Clinical and radiological outcome was satisfactory. 3 and 5 years after surgery, X-rays and CT scan documented the progressive development of heterotopic ossification, with gradual reduction of range of motion. A late onset heterotopic ossification can neutralize the theoretical advantages of cervical arthroplasty, which should be considered an effective surgical option only in selected cases. ACDF and restoration of normal lordosis can be a viable alternative in cervical revision surgery, as motion preservation can not be always mantained for a long time.

  11. Differences between 1- and 2-level cervical arthroplasty: more heterotopic ossification in 2-level disc replacement: Clinical article.

    PubMed

    Wu, Jau-Ching; Huang, Wen-Cheng; Tsai, Hsiao-Wen; Ko, Chin-Chu; Fay, Li-Yu; Tu, Tsung-Hsi; Wu, Ching-Lan; Cheng, Henrich

    2012-06-01

    The most currently accepted indication for cervical arthroplasty is 1- or 2-level degenerative disc disease (DDD) refractory to medical treatment. However, the randomized and controlled clinical trials by the US FDA investigational device exemption studies only compared cervical arthroplasty with anterior cervical discectomy and fusion for 1-level disease. Theoretically, 2-level cervical spondylosis usually implicates more advanced degeneration, whereas the 1-level DDD can be caused by merely a soft-disc herniation. This study aimed to investigate the differences between 1- and 2-level cervical arthroplasty. The authors analyzed data obtained in 87 consecutive patients who underwent 1- or 2-level cervical arthroplasty with Bryan disc. The patients were divided into the 1-level and the 2-level treatment groups. Clinical outcomes were measured using the visual analog scale (VAS) for the neck and arm pain and the Neck Disability Index (NDI), with a minimum follow-up of 30 months. Radiographic outcomes were evaluated on both radiographs and CT scans. The study analyzed 98 levels of Bryan cervical arthroplasty in 70 patients (80.5%) who completed the evaluations in a mean follow-up period of 46.21 ± 9.85 months. There were 22 females (31.4%) and 48 males (68.6%), whose mean age was 46.57 ± 10.07 years at the time of surgery. The 1-level group had 42 patients (60.0%), while the 2-level group had 28 patients (40.0%). Patients in the 1-level group were younger than those in the 2-level group (mean 45.00 vs 48.93 years, p = 0.111 [not significant]). Proportional sex compositions and perioperative prescription of nonsteroidal antiinflammatory drugs were also similar in both groups (p = 0.227 and p = 1.000). The 2-level group had significantly greater EBL during surgery than the 1-level group (220.80 vs 111.89 ml, p = 0.024). Heterotopic ossification was identified more frequently in the 2-level group than the 1-level group (75.0% vs 40.5%, p = 0.009). Although most of the

  12. Endoscopic Extra-articular Surgical Removal of Heterotopic Ossification of the Rectus Femoris Tendon in a Series of Athletes

    PubMed Central

    Comba, Fernando; Piuzzi, Nicolás S.; Oñativia, José Ignacio; Zanotti, Gerardo; Buttaro, Martín; Piccaluga, Francisco

    2016-01-01

    Background: Calcific deposits in tendon, muscles, and periarticular areas are very common. Heterotopic ossification of the rectus femoris (HORF) is a rare condition, and several theories exist regarding the etiopathogenesis, which appears to be multifactorial with traumatic, genetic, and local metabolic factors involved. Although HORF typically responds to nonoperative treatment, when this approach fails, endoscopic treatment is a minimally invasive technique to address the pathology. Purpose: To report the clinical and radiological outcomes of 9 athletes with HORF who underwent endoscopic resection. Study Design: Case series; Level of evidence, 4. Methods: Nine male athletes were treated with endoscopic extra-articular resection of HORF after failure of a 6-month course of nonoperative treatment. All patients were studied with radiographs, computed tomography, and magnetic resonance imaging. Outcomes were assessed clinically using the modified Harris Hip Score (mHHS), a visual analog scale for sport activity–related pain (VAS-SRP), patient satisfaction, and ability and time to return to the preoperative sport level. Radiographic assessment was performed to determine recurrence. Results: The mean age of the patients was 32 years (range, 23-47 years). Mean follow-up was 44 months (range, 14-73 months). All patients had improved mHHS scores from a mean preoperative of 65.6 (SD, 8.2) to 93.9 (SD, 3.6). Pain decreased from a mean 8.2 preoperatively (SD, 0.9) to 0.4 (SD, 0.7) at last follow-up. There were no complications, and all patients were able to return to their previous sports at the same level except for 1 recreational athlete. There was only 1 radiological recurrence at last follow-up in an asymptomatic patient. Conclusion: To our knowledge, this is the largest case series of athletes with HORF treated with endoscopic resection. We found this extra-articular endoscopic technique to be safe and effective, showing clinical outcome improvement and 90% chance of

  13. Endoscopic Extra-articular Surgical Removal of Heterotopic Ossification of the Rectus Femoris Tendon in a Series of Athletes.

    PubMed

    Comba, Fernando; Piuzzi, Nicolás S; Oñativia, José Ignacio; Zanotti, Gerardo; Buttaro, Martín; Piccaluga, Francisco

    2016-09-01

    Calcific deposits in tendon, muscles, and periarticular areas are very common. Heterotopic ossification of the rectus femoris (HORF) is a rare condition, and several theories exist regarding the etiopathogenesis, which appears to be multifactorial with traumatic, genetic, and local metabolic factors involved. Although HORF typically responds to nonoperative treatment, when this approach fails, endoscopic treatment is a minimally invasive technique to address the pathology. To report the clinical and radiological outcomes of 9 athletes with HORF who underwent endoscopic resection. Case series; Level of evidence, 4. Nine male athletes were treated with endoscopic extra-articular resection of HORF after failure of a 6-month course of nonoperative treatment. All patients were studied with radiographs, computed tomography, and magnetic resonance imaging. Outcomes were assessed clinically using the modified Harris Hip Score (mHHS), a visual analog scale for sport activity-related pain (VAS-SRP), patient satisfaction, and ability and time to return to the preoperative sport level. Radiographic assessment was performed to determine recurrence. The mean age of the patients was 32 years (range, 23-47 years). Mean follow-up was 44 months (range, 14-73 months). All patients had improved mHHS scores from a mean preoperative of 65.6 (SD, 8.2) to 93.9 (SD, 3.6). Pain decreased from a mean 8.2 preoperatively (SD, 0.9) to 0.4 (SD, 0.7) at last follow-up. There were no complications, and all patients were able to return to their previous sports at the same level except for 1 recreational athlete. There was only 1 radiological recurrence at last follow-up in an asymptomatic patient. To our knowledge, this is the largest case series of athletes with HORF treated with endoscopic resection. We found this extra-articular endoscopic technique to be safe and effective, showing clinical outcome improvement and 90% chance of return to full activity. We also found 10% recurrence rate of

  14. Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis

    PubMed Central

    Suzuki, Hidetsugu; Ito, Yoshiaki; Shinohara, Masahiro; Yamashita, Satoshi; Ichinose, Shizuko; Kishida, Akio; Oyaizu, Takuya; Kayama, Tomohiro; Nakamichi, Ryo; Koda, Naoki; Yagishita, Kazuyoshi; Lotz, Martin K.; Okawa, Atsushi; Asahara, Hiroshi

    2016-01-01

    Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particular, precise physiological examination for mechanical load and the ability to obtain a sufficient number of primary tendon cells for molecular biology studies are challenging using mice. Here, we generated Mohawk (Mkx)−/− rats by using CRISPR/Cas9, which showed not only systemic hypoplasia of tendons similar to Mkx−/− mice, but also earlier heterotopic ossification of the Achilles tendon compared with Mkx−/− mice. Analysis of tendon-derived cells (TDCs) revealed that Mkx deficiency accelerated chondrogenic and osteogenic differentiation, whereas Mkx overexpression suppressed chondrogenic, osteogenic, and adipogenic differentiation. Furthermore, mechanical stretch stimulation of Mkx−/− TDCs led to chondrogenic differentiation, whereas the same stimulation in Mkx+/+ TDCs led to formation of tenocytes. ChIP-seq of Mkx overexpressing TDCs revealed significant peaks in tenogenic-related genes, such as collagen type (Col)1a1 and Col3a1, and chondrogenic differentiation-related genes, such as SRY-box (Sox)5, Sox6, and Sox9. Our results demonstrate that Mkx has a dual role, including accelerating tendon differentiation and preventing chondrogenic/osteogenic differentiation. This molecular network of Mkx provides a basis for tendon physiology and tissue engineering. PMID:27370800

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

    SciTech Connect

    Balboni, Tracy A.; Gaccione, Peter; Gobezie, Reuben; Mamon, Harvey J. . E-mail: hmamon@partners.org

    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 eligible 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.

  16. The roles of serum alkaline and bone alkaline phosphatase levels in predicting heterotopic ossification following spinal cord injury.

    PubMed

    Citak, M; Grasmücke, D; Suero, E M; Cruciger, O; Meindl, R; Schildhauer, T A; Aach, M

    2016-05-01

    Retrospective chart review. To analyze the usefulness of serum alkaline phosphatase (AP) and bone alkaline phosphatase (BAP), as well as C-reactive protein (CRP) levels in predicting heterotopic ossification (HO). Department of Spinal Cord Injury and Department of General and Trauma Surgery, BG-University Hospital Bergmannsheil, Ruhr University Bochum, Germany. Between January 2003 and December 2013, 87 patients with HO around the hips met the inclusion criteria and were included in the study. Alkaline phosphatase, CRP and BAP were assessed and interpreted at the time of HO diagnosis and after radiation therapy in all patients. At the time of HO diagnosis, 49 out of 87 patients (49.4%) had elevated alkaline phosphatase levels and 39 out of 87 patients (44.8%) had elevated BAP levels. Elevated CRP values were found in 67 patients (77.0%). Within 3 days after single-dose radiation therapy, elevated AP levels persisted in 38 patients (43.7%) and elevated BAP levels in 28 patients (32.2%). The results obtained show that the determination of CRP, AP and BAP levels may not be considered a reliable screening method for early HO detection, subsequent to spinal cord injury.

  17. 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

  18. Determining early markers of disease using Raman spectroscopy in a rat combat-trauma model of heterotopic ossification

    NASA Astrophysics Data System (ADS)

    Cilwa, Katherine E.; Qureshi, Ammar T.; Forsberg, Jonathan A.; Davis, Thomas A.; Crane, Nicole J.

    2016-02-01

    Traumatic heterotopic ossification (HO) is the pathological formation of bone in soft tissue and is a debilitating sequela following acute trauma involving blast-related extremity musculoskeletal injuries, severe burns, spinal cord injury, and traumatic brain injury. Over 60% of combat related injuries and severe burns develop HO; often resulting in reduced mobility, chronic pain, ulceration, tissue entrapment, and reduced ambulation. Detection and prognosis is limited by current clinical imaging modalities (computed tomography, radiography, and ultrasound). This study identifies Raman spectral signatures corresponding to histological changes in a combat-trauma induced rat HO model at early time points prior to radiographic evidence of HO. HO was induced in Sprague-Dawley rats via blast over pressure injury, mid-femoral fracture, soft tissue crush injury, and limb amputation through the zone of injury. Rats were euthanized, and amputated limbs were formalin fixed and embedded in paraffin; 10 μm sections were placed on gold slides, and paraffin was chemically removed. Tissues from sham-treated animals served as controls. Tissue maps consisting of Raman spectra were generated using a Raman microprobe system with an 80-90 μm spot size and 785 nm excitation in regions exhibiting histological evidence of early HO development according to adjacent HE sections. Factors were extracted from mapping data using Band-Target Entropy Minimization algorithms. Areas of early HO were highlighted by a Raman factor indicative of the presence of collagen. Identification of collagen as an early marker of HO prior to radiographic detection in a clinically relevant animal model serves to inform future clinical work.

  19. Sustained delivery of rhBMP-2 via PLGA microspheres: cranial bone regeneration without heterotopic ossification or craniosynostosis

    PubMed Central

    Wink, Jason D.; Gerety, Patrick A.; Sherif, Rami D.; Lim, Youngshin; A.Clarke, Nadya; Rajapakse, Chamith S.; Nah, Hyun-Duck; Taylor, Jesse A.

    2014-01-01

    Background Commercially available recombinant human bone morphogenetic protein 2 (rhBMP2) has demonstrated efficacy in bone regeneration, but not without significant side effects. In this study, we utilize rhBMP2 encapsulated in PLGA microspheres (PLGA-rhBMP2) placed in a rabbit cranial defect model to test whether low-dose, sustained, delivery can effectively induce bone regeneration. Methods rhBMP2 was encapsulated in 15% poly (lactic-co-glycolic acid), using a double emulsion, solvent extraction/evaporation technique, and its release kinetics and bioactivity were tested. Two critical-size defects (10mm) were created in the calvarium of New Zealand White rabbits (5-7 mos of age, M/F) and filled with a collagen scaffold containing one of four groups: 1) no implant, 2) collagen scaffold only, 3) PLGA-rhBMP2(0.1ug/implant), or 4) free rhBMP2 (0.1ug/implant). After 6 weeks, the rabbits were sacrificed and defects were analyzed by μCT, histology, and finite element analysis. Results RhBMP2 delivered via bioactive PLGA microspheres resulted in higher volumes and surface area coverage of new bone than an equal dose of free rhBMP2 by μCT and histology (p=0.025, 0.025). FEA indicated that the mechanical competence using the regional elastic modulus did not differ with rhBMP2 exposure (p=0.70). PLGA-rhBMP2 did not demonstrate heterotopic ossification, craniosynostosis, or seroma formation. Conclusions Sustained delivery via PLGA microspheres can significantly reduce the rhBMP2 dose required for de novo bone formation. Optimization of the delivery system may be a key to reduce the risk for recently reported rhBMP2 related adverse effects. Level of Evidence Animal Study PMID:24622573

  20. Heterotopic ossification of the knee joint in intensive care unit patients: early diagnosis with magnetic resonance imaging

    PubMed Central

    Argyropoulou, Maria I; Kostandi, Eleonora; Kosta, Paraskevi; Zikou, Anastasia K; Kastani, Dimitra; Galiatsou, Efi; Kitsakos, Athanassios; Nakos, George

    2006-01-01

    Introduction Heterotopic ossification (HO) is the formation of bone in soft tissues. The purpose of the present study was to evaluate the magnetic resonance imaging (MRI) findings on clinical suspicion of HO in the knee joint of patients hospitalised in the intensive care unit (ICU). Methods This was a case series of 11 patients requiring prolonged ventilation in the ICU who had the following diagnoses: head trauma (nine), necrotising pancreatitis (one), and fat embolism (one). On clinical suspicion of HO, x-rays and MRI of the knee joint were performed. Follow-up x-rays and MRI were also performed. Results First x-rays were negative, whereas MRI (20.2 ± 6.6 days after admission) showed joint effusion and in fast spin-echo short time inversion-recovery (STIR) images a 'lacy pattern' of the muscles vastus lateralis and medialis. The innermost part of the vastus medialis exhibited homogeneous high signal. Contrast-enhanced fat-suppressed T1-weighted images also showed a 'lacy pattern.' On follow-up (41.4 ± 6.6 days after admission), STIR and contrast-enhanced T1-weighted images depicted heterogeneous high signal and heterogeneous enhancement, respectively, at the innermost part of the vastus medialis, whereas x-rays revealed a calcified mass in the same position. Overall, positive MRI findings appeared simultaneously with clinical signs (1.4 ± 1.2 days following clinical diagnosis) whereas x-ray diagnosis was evident at 23 ± 4.3 days (p = 0.002). Conclusion MRI of the knee performed on clinical suspicion shows a distinct imaging pattern confirming the diagnosis of HO earlier than other methods. MRI diagnosis may have implications for early intervention in the development of HO. PMID:17074077

  1. 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.

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

    SciTech Connect

    Mourad, Waleed F.; Packianathan, Satyaseelan; Shourbaji, Rania A.; Zhang Zhen; Graves, Mathew; Khan, Majid A.; Baird, Michael C.; Russell, George; Vijayakumar, Srinivasan

    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 patients 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.

  3. A sciatic nerve lesion secondary to compression by a heterotopic ossification in the hip and thigh region--an electrodiagnostic approach.

    PubMed

    Abayev, Boris; Ha, Edward; Cruise, Cathy

    2005-05-01

    A sciatic nerve lesion secondary to compression by a heterotopic ossification is rare. Operative release of the encased sciatic nerve in some cases may restore the function of the nerve partially or completely. However, in some cases the injury may be permanent. An electrophysiologic study is very useful to determine the location and severity of nerve damage, including axonal loss, demyelination, or both. An electrophysiologic study can emphasize the portion of the sciatic nerve that has been involved the most (lateral versus medial or peroneal versus tibial). In some cases an electrophysiologic study can suggest whether surgery should be postponed if a recovery pattern from the nerve injury is obvious. The prognostic value of follow-up studies is considerable. The authors reviewed literature available to them since 1971 and found 6 cases, including their own. This is the first attempt to put together all the information available in the literature about this condition.

  4. Idiopathic heterotopic ossification of bilateral subscapularis tendons: illustration of a rare entity and a concise literature review.

    PubMed

    Arora, Richa

    2016-08-01

    Ossification of the subscapularis tendon is an extremely uncommon, poorly described lesion with little known about its etiopathogenesis and clinical significance. To the best of our knowledge, only three cases of this entity have been reported till now, which were all unilateral. The authors present first case of ossification of bilateral subscapularis tendons in a 57-year-old male and hope that with increase in the number of reported cases, proper guidelines for management of such cases can be formulated.

  5. Idiopathic heterotopic ossification of bilateral subscapularis tendons: illustration of a rare entity and a concise literature review

    PubMed Central

    2016-01-01

    Ossification of the subscapularis tendon is an extremely uncommon, poorly described lesion with little known about its etiopathogenesis and clinical significance. To the best of our knowledge, only three cases of this entity have been reported till now, which were all unilateral. The authors present first case of ossification of bilateral subscapularis tendons in a 57-year-old male and hope that with increase in the number of reported cases, proper guidelines for management of such cases can be formulated. PMID:27709080

  6. Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation.

    PubMed

    Chakkalakal, Salin A; Uchibe, Kenta; Convente, Michael R; Zhang, Deyu; Economides, Aris N; Kaplan, Frederick S; Pacifici, Maurizio; Iwamoto, Masahiro; Shore, Eileen M

    2016-09-01

    Fibrodysplasia ossificans progressiva (FOP), a rare and as yet untreatable genetic disorder of progressive extraskeletal ossification, is the most disabling form of heterotopic ossification (HO) in humans and causes skeletal deformities, movement impairment, and premature death. Most FOP patients carry an activating mutation in a bone morphogenetic protein (BMP) type I receptor gene, ACVR1(R206H) , that promotes ectopic chondrogenesis and osteogenesis and, in turn, HO. We showed previously that the retinoic acid receptor γ (RARγ) agonist palovarotene effectively inhibited HO in injury-induced and genetic mouse models of the disease. Here we report that the drug additionally prevents spontaneous HO, using a novel conditional-on knock-in mouse line carrying the human ACVR1(R206H) mutation for classic FOP. In addition, palovarotene restored long bone growth, maintained growth plate function, and protected growing mutant neonates when given to lactating mothers. Importantly, palovarotene maintained joint, limb, and body motion, providing clear evidence for its encompassing therapeutic potential as a treatment for FOP. © 2016 American Society for Bone and Mineral Research.

  7. Effects of blockade of endogenous Gi signaling in Tie2-expressing cells on bone formation in a mouse model of heterotopic ossification.

    PubMed

    Wang, Liping; Carroll, Dylan O'; Liu, Xuhui; Roth, Theresa; Kim, Hubert; Halloran, Bernard; Nissenson, Robert A

    2015-08-01

    Available evidence indicates that some Tie2-expressing (Tie2(+) ) cells serve as multipotent progenitors that have robust BMP-dependent osteogenic activity and mediate heterotopic ossification (HO). Since signaling through the G protein Gi is required for cell motility, we hypothesized that blockade of endogenous Gi signaling in Tie2(+) cell populations would prevent HO formation. Blockade of Gi signaling in Tie2(+) cells was accomplished in transgenic mice with expression of pertussis toxin (PTX) under the control of the Tie2 promoter (Tie2(+) /PTX(+) ). Bone formation within HOs was evaluated 2 weeks after BMP injection. Expression of PTX in Tie2(+) cells significantly reduced the bone volume (BV) of HOs in male and female mice. Orthotopic bones were assessed at the distal femur and expression of PTX significantly increased trabecular bone fractional volume and bone formation rate in females only. In adult Tie2(+) /GFP(+) mice, GFP(+) cells appeared both inside and at the surfaces of bone tissue within HOs and in orthotopic bones. In summary, blockade of Gi signaling in Tie2(+) cells reduced the accrual of HOs and stimulated osteogenesis in orthotopic bones. Targeting of Gi protein coupled receptors in Tie2(+) cells may be a novel therapeutic strategy in states of abnormal bone formation such as osteoporosis and HO. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  8. Developing a Quantitative Measurement System for Assessing Heterotopic Ossification and Monitoring the Bioelectric Metrics from Electrically Induced Osseointegration in the Residual Limb of Service Members

    PubMed Central

    Isaacson, Brad M.; Stinstra, Jeroen G.; MacLeod, Rob S.; Pasquina, Paul F.; Bloebaum, Roy D.

    2011-01-01

    Poor prosthetic fit is often the result of heterotopic ossification (HO), a frequent problem following blast injuries for returning service members. Osseointegration technology offers an advantage for individuals with significant HO and poor socket tolerance by using direct skeletal attachment of a prosthesis to the distal residual limb, but remains limited due to prolonged post-operative rehabilitation regimens. Therefore, electrical stimulation has been proposed as a catalyst for expediting skeletal attachment and the bioelectric effects of HO were evaluated using finite element analysis in 11 servicemen with transfemoral amputations. Retrospective computed tomography (CT) scans provided accurate reconstructions, and volume conductor models demonstrated the variability in residual limb anatomy and necessity for patient-specific modeling to characterize electrical field variance if patients were to undergo a theoretical osseointegration of a prosthesis. In this investigation, the volume of HO was statistically significant when selecting the optimal potential difference for enhanced skeletal fixation, since higher HO volumes required increased voltages at the periprosthetic bone (p = 0.024, r = 0.670). Results from Spearman’s rho correlations also indicated that the age of the subject and volume of HO were statistically significant and inversely proportional, in which younger service members had a higher frequency of HO (p = 0.041, r = −0.622). This study demonstrates that the volume of HO and age may affect the voltage threshold necessary to improve current osseointegration procedures. PMID:20458630

  9. Developing a quantitative measurement system for assessing heterotopic ossification and monitoring the bioelectric metrics from electrically induced osseointegration in the residual limb of service members.

    PubMed

    Isaacson, Brad M; Stinstra, Jeroen G; MacLeod, Rob S; Pasquina, Paul F; Bloebaum, Roy D

    2010-09-01

    Poor prosthetic fit is often the result of heterotopic ossification (HO), a frequent problem following blast injuries for returning service members. Osseointegration technology offers an advantage for individuals with significant HO and poor socket tolerance by using direct skeletal attachment of a prosthesis to the distal residual limb, but remains limited due to prolonged post-operative rehabilitation regimens. Therefore, electrical stimulation has been proposed as a catalyst for expediting skeletal attachment and the bioelectric effects of HO were evaluated using finite element analysis in 11 servicemen with transfemoral amputations. Retrospective computed tomography (CT) scans provided accurate reconstructions, and volume conductor models demonstrated the variability in residual limb anatomy and necessity for patient-specific modeling to characterize electrical field variance if patients were to undergo a theoretical osseointegration of a prosthesis. In this investigation, the volume of HO was statistically significant when selecting the optimal potential difference for enhanced skeletal fixation, since higher HO volumes required increased voltages at the periprosthetic bone (p = 0.024, r = 0.670). Results from Spearman's rho correlations also indicated that the age of the subject and volume of HO were statistically significant and inversely proportional, in which younger service members had a higher frequency of HO (p = 0.041, r = -0.622). This study demonstrates that the volume of HO and age may affect the voltage threshold necessary to improve current osseointegration procedures.

  10. Prevalence and risk-factors of neurogenic heterotopic ossification in traumatic spinal cord and traumatic brain injured patients admitted to specialised units in Australia.

    PubMed

    Reznik, J E; Biros, E; Marshall, R; Jelbart, M; Milanese, S; Gordon, S; Galea, M P

    2014-03-01

    To identify the prevalence and risk factors in the development of Neurogenic Heterotopic Ossification (NHO) in traumatic brain and spinal cord injured patients admitted to specialised units. An audit protocol was used to gather all clinically relevant data, in specific patient groups, relating to the prevalence of NHO, and was statistically analysed to identify traumatic brain injury (TBI) and traumatic spinal cord injury (TSCI) patients at high risk of developing NHO. 262 TBI and 151 TSCI patients were identified. NHO was diagnosed in 10 and 16 patients with TBI and TSCI, respectively; 18 clinically relevant characteristics were analysed for association with NHO in these patient groups. The only common variables associated with NHO in both neurological conditions were deep vein thrombosis and/or pulmonary emboli (DVT/PE). The prevalence of NHO in TBI patients is less than one-third of that found in TSCI patients, ~4% and 11%, respectively. This study also suggests that the risk factors associated with NHO in TBI patients are distinct from those identified as risk factors in TSCI patients.

  11. Differences between C3-4 and other subaxial levels of cervical disc arthroplasty: more heterotopic ossification at the 5-year follow-up.

    PubMed

    Chang, Peng-Yuan; Chang, Hsuan-Kan; Wu, Jau-Ching; Huang, Wen-Cheng; Fay, Li-Yu; Tu, Tsung-Hsi; Wu, Ching-Lan; Cheng, Henrich

    2016-05-01

    OBJECTIVE Several large-scale clinical trials demonstrate the efficacy of 1- and 2-level cervical disc arthroplasty (CDA) for degenerative disc disease (DDD) in the subaxial cervical spine, while other studies reveal that during physiological neck flexion, the C4-5 and C5-6 discs account for more motion than the C3-4 level, causing more DDD. This study aimed to compare the results of CDA at different levels. METHODS After a review of the medical records, 94 consecutive patients who underwent single-level CDA were divided into the C3-4 and non-C3-4 CDA groups (i.e., those including C4-5, C5-6, and C6-7). Clinical outcomes were measured using the visual analog scale for neck and arm pain and by the Japanese Orthopaedic Association scores. Postoperative range of motion (ROM) and heterotopic ossification (HO) were determined by radiography and CT, respectively. RESULTS Eighty-eight patients (93.6%; mean age 45.62 ± 10.91 years), including 41 (46.6%) female patients, underwent a mean follow-up of 4.90 ± 1.13 years. There were 11 patients in the C3-4 CDA group and 77 in the non-C3-4 CDA group. Both groups had significantly improved clinical outcomes at each time point after the surgery. The mean preoperative (7.75° vs 7.03°; p = 0.58) and postoperative (8.18° vs 8.45°; p = 0.59) ROMs were similar in both groups. The C3-4 CDA group had significantly greater prevalence (90.9% vs 58.44%; p = 0.02) and higher severity grades (2.27 ± 0.3 vs 0.97 ± 0.99; p = 0.0001) of HO. CONCLUSIONS Although CDA at C3-4 was infrequent, the improved clinical outcomes of CDA were similar at C3-4 to that in the other subaxial levels of the cervical spine at the approximately 5-year follow-ups. In this Asian population, who had a propensity to have ossification of the posterior longitudinal ligament, there was more HO formation in patients who received CDA at the C3-4 level than in other subaxial levels of the cervical spine. While the type of artificial discs could have confounded the

  12. Dynamics of MMP‑9, MMP‑2 and TIMP‑1 in a rat model of brain injury combined with traumatic heterotopic ossification.

    PubMed

    Shi, Wei-Zhe; Ju, Jin-Yong; Xiao, Hai-Jun; Xue, Feng; Wu, Jiang; Pan, Ming-Mang; Ni, Wei-Feng

    2017-04-01

    The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase‑2 (MMP‑2) and tissue inhibitor of metalloproteinase‑1 (TIMP‑1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132 male Sprague‑Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin and eosin and immunohistochemical staining were performed for local tissues. MMP‑9, MMP‑2 and TIMP‑1 levels and gene expression level were measured by ELISA and reverse transcription‑quantitative polymerase chain reaction. Radiological investigation of the rat lower limbs was conducted at weeks 5 and 10 following modeling to observe the occurrence of HO. The incidence of HO for rats in the experimental group was higher compared with the control group. The serum MMP‑9 levels of the experimental group were notably higher on postoperative days 5‑7 compared with the control group. The MMP‑9 gene expression of the experimental group was higher on postoperative days 3‑7 compared with the control group. The TIMP‑1 gene expression levels were markedly higher compared with the control group at each time point. Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP‑9 and the altered dynamic equilibrium between MMP‑9 and TIMP‑1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP‑9 is a predictive marker of HO.

  13. 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.

  14. 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.

  15. Blast Injuries And Heterotopic Ossification

    DTIC Science & Technology

    2012-08-01

    went further to demonstrate that mouse mesenchymal stem cells , when treated with RAR-γ agonist in vitro, lost the ability to differ- entiate into...continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic...including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using

  16. Preventative Therapeutics for Heterotopic Ossification

    DTIC Science & Technology

    2014-10-01

    One of the most effective RARγ agonists we used was R667 (Palovarotene), previously tested for long-term treatment of a chronic disease ( emphysema ) in...Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema . Curr. Opin. Invest. Drugs 10:1243-1250. 29. Koyama N, Okubo

  17. Preventative Therapeutics for Heterotopic Ossification

    DTIC Science & Technology

    2014-10-01

    Quantitative RT-PCR (qRT-PCR) was used to analyze tissue samples for the expression of 83 rat osteogenic, chondrogenic, adipogenic , and angiogenic gene ...injury, ectopic bone, palovarotene, amputation, combat wounds, crush injury, bioburden, osteogenesis, chondrogenesis, gene expression, extremity...related traumatic injury;(2) the blast-related gene expression patterns in traumatized tissues subsequent to calcium deposition, tissue mineralization and

  18. Heterotopic Ossification in Wartime Wounds

    DTIC Science & Technology

    2010-01-01

    Institute, Washington, DC, 2008. 105. Ehde, D. M .• Smith, D. G. Chronic pain management. In Atlas of Amputations and Limb Deficiencies : Surgical...bone for growth within the residual limbs of amputees is an important recent observation (24, 26). Definitive amputations are often performed within...complicate up to 64% of patients, has a predilection for the residual limbs of amputees, and remains a significant source of disability. Although the

  19. Postoperative nonsteroidal antiinflammatory drugs and the prevention of heterotopic ossification after cervical arthroplasty: analysis using CT and a minimum 2-year follow-up.

    PubMed

    Tu, Tsung-Hsi; Wu, Jau-Ching; Huang, Wen-Cheng; Chang, Hsuan-Kan; Ko, Chin-Chu; Fay, Li-Yu; Wu, Ching-Lan; Cheng, Henrich

    2015-05-01

    OBJECT Heterotopic ossification (HO) after cervical arthroplasty is not uncommon and may cause immobility of the disc. To prevent HO formation, study protocols of clinical trials for cervical arthroplasty undertaken by the US FDA included perioperative use of nonsteroidal antiinflammatory drugs (NSAIDs). However, there are few data supporting the use of NSAIDs to prevent HO after cervical arthroplasty. Therefore, this study aimed to evaluate the efficacy of NSAIDs in HO formation and clinical outcomes. METHODS Consecutive patients who underwent 1- or 2-level cervical arthroplasty with a minimum follow-up of 24 months were retrospectively reviewed. All patients were grouped into 1 of 2 groups, an NSAID group (those patients who had used NSAIDs postoperatively) and a non-NSAID group (those patients who had not used NSAIDs postoperatively). The formation of HO was detected and classified using CT in every patient. The incidence of HO formation, disc mobility, and clinical outcomes, including visual analog scale (VAS) scores of neck and arm pain, neck disability index (NDI) scores, and complications were compared between the two groups. Furthermore, a subgroup analysis of the patients in the NSAID group, comparing the selective cyclooxygenase (COX)-2 to nonselective COX-2 NSAID users, was also conducted for each of the above-mentioned parameters. RESULTS A total of 75 patients (mean age [± SD] 46.71 ± 9.94 years) with 107 operated levels were analyzed. The mean follow-up duration was 38.71 ± 9.55 months. There were no significant differences in age, sex, and levels of arthroplasty between the NSAID and non-NSAID groups. There was a nonsignificantly lower rate of HO formation in the NSAID group than the non-NSAID group (47.2% vs. 68.2%, respectively; p = 0.129). During follow-up, most of the arthroplasty levels remained mobile, with similar rates of immobile discs in the NSAID and non-NSAID groups (13.2% and 22.7%, respectively; p = 0.318). Furthermore, there was a

  20. 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

    injured in Operation Iraqi Freedom and Opera- tion Enduring Freedom, or Iraq and Afghanistan wars, respec- tively. HO can interfere with prosthetic use...interviews to document evidence of HO symptoms in these limbs (e.g., pain during prosthetic use, skin breakdown). Results showed HO-related symptoms...finding of potential benefits of HO for prosthetic suspension. Key words: Afghanistan war, amputation, blast injury, combat amputee, heterotopic

  1. Heterotopic ossification following single-level anterior cervical discectomy and fusion: results from the prospective, multicenter, historically controlled trial comparing allograft to an optimized dose of rhBMP-2.

    PubMed

    Arnold, Paul M; Anderson, Karen K; Selim, Abdulhafez; Dryer, Randall F; Kenneth Burkus, J

    2016-09-01

    OBJECTIVE Heterotopic ossification (HO) has been reported following total hip, knee, cervical, and lumbar arthroplasty, as well as following posterolateral lumbar fusion using recombinant human bone morphogenetic protein-2 (rhBMP-2). Data regarding HO following anterior cervical discectomy and fusion (ACDF) with rhBMP-2 are sparse. A subanalysis was done of the prospective, multicenter, investigational device exemption trial that compared rhBMP-2 on an absorbable collagen sponge (ACS) versus allograft in ACDF for patients with symptomatic single-level cervical degenerative disc disease. METHODS To assess differences in types of HO observed in the treatment groups and effects of HO on functional and efficacy outcomes, clinical outcomes from previous disc replacement studies were compared between patients who received rhBMP-2/ACS versus allograft. Rate, location, grade, and size of ossifications were assessed preoperatively and at 24 months, and correlated with clinical outcomes. RESULTS Heterotopic ossification was primarily anterior in both groups. Preoperatively in both groups, and including osteophytes in the target regions, HO rates were high at 40.9% and 36.9% for the rhBMP-2/ACS and allograft groups, respectively (p = 0.350). At 24 months, the rate of HO in the rhBMP-2/ACS group was higher than in the allograft group (78.6% vs 59.2%, respectively; p < 0.001). At 24 months, the rate of superior-anterior adjacent-level Park Grade 3 HO was 4.2% in both groups, whereas the rate of Park Grade 2 HO was 19.0% in the rhBMP-2/ACS group compared with 9.8% in the allograft group. At 24 months, the rate of inferior-anterior adjacent-level Park Grade 2/3 HO was 11.9% in the rhBMP-2/ACS group compared with 5.9% in the allograft group. At 24 months, HO rates at the target implant level were similar (p = 0.963). At 24 months, the mean length and anteroposterior diameter of HO were significantly greater in the rhBMP-2/ACS group compared with the allograft group (p = 0.033 and

  2. Diagnosis and Treatment of Heterotopic Ossification

    DTIC Science & Technology

    2015-10-01

    on specialized endothelial cells within the endoneurium and is responsible for forming the tight junction of blood nerve interface. We are further...Yosef et al [Yosef and Ubogu] reported the unique expression of the tight junction molecule, claudin 5, on specialized endoneurial endothelial cells...the reasons for this is that this key tight junction molecule, found exclusively in a type of endothelial cell whose relationship to other

  3. Diagnosis and Treatment of Heterotopic Ossification

    DTIC Science & Technology

    2013-10-01

    suggests blocking the initial response of the nerve could ultimately block this devastating problem before it occurs. Studies proposed in this application...to identify and isolate osterix+ cells have led us to identify a second tentative progenitor within peripheral nerves . These cells reside in the... nerve interface. We are further characterizing these cells for expression of endothelial markers. We also looked at the expression of Wnt1, a marker

  4. Diagnosis and Treatment of Heterotopic Ossification

    DTIC Science & Technology

    2014-10-01

    hours after induction of HO possess characteristics of a neural crest stem cell observed migrating in the embryo to form the bones of the head and...similarly to iPs cells. If these cells appear positive in this assay, we will then subject them to a chick assay in which we generate a chimeric embryo ...and circumventing this problem. However here, we note that MMP9 activation is through cleavage by plasmin. Plasmin is produced by the liver, and

  5. Inherited human diseases of heterotopic bone formation

    PubMed Central

    Shore, Eileen M.; Kaplan, Frederick S.

    2013-01-01

    Human disorders of hereditary and nonhereditary heterotopic ossification are conditions in which osteogenesis occurs outside of the skeleton, within soft tissues of the body. The resulting extraskeletal bone is normal. The aberration lies within the mechanisms that regulate cell-fate determination, directing the inappropriate formation of cartilage or bone, or both, in tissues such as skeletal muscle and adipose tissue. Specific gene mutations have been identified in two rare inherited disorders that are clinically characterized by extensive and progressive extraskeletal bone formation—fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In fibrodysplasia ossificans progressiva, activating mutations in activin receptor type-1, a bone morphogenetic protein type I receptor, induce heterotopic endochondral ossification, which results in the development of a functional bone organ system that includes skeletal-like bone and bone marrow. In progressive osseous heteroplasia, the heterotopic ossification leads to the formation of mainly intramembranous bone tissue in response to inactivating mutations in the GNAS gene. Patients with these diseases variably show malformation of normal skeletal elements, identifying the causative genes and their associated signaling pathways as key mediators of skeletal development in addition to regulating cell-fate decisions by adult stem cells. PMID:20703219

  6. Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties

    SciTech Connect

    Jasty, M.; Schutzer, S.; Tepper, J.; Willett, C.; Stracher, M.A.; Harris, W.H. )

    1990-08-01

    Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

  7. Operative treatment of anterior heterotopic bone formation of the elbow in a patient with severe haemophilia A.

    PubMed

    Mortazavi, S M J; Asadollahi, S; Motamedi, M

    2006-07-01

    There is no statistical data on the incidence of heterotopic ossification among patients with haemophilia, and a few reports documenting this entity in haemophilia are available. Although post-traumatic heterotopic ossification about the elbow is a well-recognized complication, we are not aware of any previously reported case in haemophiliacs. An 8-year-old boy with severe haemophilia A presented with fixed elbow in 80 degrees of flexion. Radiographs disclosed a mature anterior heterotopic ossification in the form of complete ulnohumeral bony bridge. Surgical excision of the heterotopic bone was performed. A full elbow range of motion was obtained after long-term physiotherapy. We conclude that this surgery is safe and successful in haemophilic patients, if performed at the right time under optimal situation.

  8. A rare, low-grade appendiceal mucinous neoplasm (Pseudomyxoma peritonei) with ossification: A case report with morphoproteomic analysis of bone formation.

    PubMed

    Noh, Byeong-Joo; Kim, Youn Wha; Park, Yong-Koo

    2016-11-01

    Heterotopic ossification occurring to low-grade appendiceal mucinous neoplasm (LAMN) (pseudomyxoma peritonei) is extremely rare. The pathogenetic mechanism of the tumor-related heterotopic bone formation remains as yet unconfirmed. Here, we describe a rare case of LAMN with ossification in a 72-year-old woman, and concentrate on the etiology of heterotopic ossification by the immunohistochemical evaluation of the novel markers such as BMP9, osteocalcin, and osteopontin. BMP9 is one of the most effective osteogenetic proteins. However, no researches associated with BMP9 in the heterotopic ossification occurring to LAMN have been performed. Consequently, we suggest the trustworthy hypothesis of tumor-associated heterotopic bone formation through this case. When osteoblastic markers such as BMP9, osteocalcin, and osteopontin are overexpressed in tumor cells, osteoblast-like transformation of such tumor cells occurs. In turn, these tumor cells increase secretion of interactive osteogenetic factors, such as BMP9, osteocalcin, and osteopontin, thus contributing to heterotopic bone formation through a microenvironmental change to mesenchymal stromal cells (osteoblastic differentiation). This phenomenon is considered a type of EMT. Patients should be followed closely because EMT-like transformed tumors have shown a tendency toward local recurrence. Our findings provide insight into the pathogenetic etiology of the heterotopic ossification in LAMN (pseudomyxoma peritonei).

  9. Heterotopic pregnancy in HIV women.

    PubMed

    Savasi, Valeria; Antonazzo, Patrizio; Personeni, Carlo

    2016-01-01

    Heterotopic pregnancy occurs when intrauterine and ectopic pregnancy are concomitant; overall rate rises from 1/30.000 to 1.5/1000 in assisted reproductive technology pregnancies. HIV (human immunodeficiency virus) patients are at increased risk of heterotopic pregnancies due to the greater frequency of assisted reproductive technology and pelvic inflammatory disease. We report the first case of heterotopic pregnancy in HIV woman.

  10. Proteomic Analysis of Trauma-Induced Heterotopic Ossification Formation

    DTIC Science & Technology

    2014-10-01

    to a special issue of Biochimie focusing on aging, metabolism and obesity. This work provides a background for additional studies whereby Dr. Martin...a special issue of the journal Biochimie . 4. CONCLUSION: Summarize the importance and/or implications with respect to medical and /or

  11. Engineered Osteoclasts for the Treatment and Prevention of Heterotopic Ossification

    DTIC Science & Technology

    2015-10-01

    for a period of 4 weeks. At the end of the 4 week period , mice underwent microCT scanning to confirm the development of HO lesions. Following the... period . Further, the efficacy of the collagen gel carrier appeared to be superior to delivery of cells in fibrin hydrogels. Consequently, for

  12. Engineered Osteoclasts for the Treatment and Prevention of Heterotopic Ossification

    DTIC Science & Technology

    2015-10-01

    BMP-Matrigel injection, the mice were allowed to ambulate freely for a period of 4 weeks. At the end of the 4 week period , mice underwent microCT...CID resulted in a decrease in HO volume over the two week study period . Further, the efficacy of the collagen gel carrier appeared to be superior to

  13. Mechanisms and Treatments of Heterotopic Ossification Following Spinal Cord Injuries

    DTIC Science & Technology

    2016-10-01

    therefore had to source cardiotoxin  from a different  supplier  (Latoxan  in  France ). Although  this cardiotoxin causes muscle damage,  in our  experiments...ParaOs  tissue banks in  France . Application for approval has been submitted to the HRPO.    Subtask 3  8    We have optimised immunohistochemical (IHC... France )  is  purified from the venom of a related but different snake species (Naja pallida). We tested the activity of  this  alternative  cardiotoxin

  14. The Contribution of Genotype to Heterotopic Ossification after Orthopaedic Trauma

    DTIC Science & Technology

    2012-06-01

    was inversely correlated with traumatic brain injury. Injury severity score, ventilator days, ICU days and total hospital days positively correlated...Vitamin D receptor 27. BMP2 28. BMP4 29. Sclerostin 30. Frizzled 9 31. FOXO1 32. FOXO3 3. Radiographs for these individuals have been examined for HO...Coma Scale (GCS) which is a more specific indicator of traumatic brain injury. The GCS on admission has inaccuracies due to intubation and medication

  15. Early Detection of Heterotopic Ossification for Effective Prevention and Treatment

    DTIC Science & Technology

    2014-04-01

    bottom 96-well plate and read at OD405 with a microplate reader. 3) Quantification of the expression of osteogenic genes with real-time PCR...25 μl. No-template and no-reverse transcription reactions were included in each PCR plate as negative controls. The housekeeping gene 18s was used as...Ct). The Ct values of the gene under investigation were first normalized, as ∆Ct, by subtraction of the Ct value of 18s. The relative expression of

  16. Proteomic Analysis of Trauma-Induced Heterotopic Ossification Formation

    DTIC Science & Technology

    2016-10-01

    Jeffrey M. Gimble MD PhD CONTRACTING ORGANIZATION: Tulane University New Orleans, LA 70118 REPORT DATE: October 2016 TYPE OF REPORT: Annual PREPARED...ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Tulane University New Orleans, LA 70118 9. SPONSORING...that can stimulate fat or muscle cells to form bone in the laboratory? This will test whether patients with HO have factors circulating in their blood

  17. Engineered Osteoclasts for the Treatment and Prevention of Heterotopic Ossification

    DTIC Science & Technology

    2014-10-01

    stereotaxic microinjection protocol that will allow us to induce HO lesions in the calf midbelly in a highly reproducible manner. The stereotaxic... protocol for the collection and storage of human HO specimens. During the next year we will begin collecting human HO samples. HO samples will be fixed...treated with AP20187 or 0.1% EtOH for 5 days. Cells were then fixed and stained for TRAP. Validation of osteoclast differentiation protocol for

  18. Engineered Osteoclasts for the Treatment and Prevention of Heterotopic Ossification

    DTIC Science & Technology

    2014-10-01

    stereotaxic microinjection protocol that will allow us to induce HO lesions in the calf midbelly in a highly reproducible manner. The stereotaxic...traumatic bone injuries. Subtask 1: Collection of human HO samples (PI: Sangeorzan, Harborview) We have currently established a protocol for...with AP20187 or 0.1% EtOH for 5 days. Cells were then fixed and stained for TRAP. Validation of osteoclast differentiation protocol for human iPS

  19. Noninvasive Imaging of Heterotopic Ossification and Targeted Intervention

    DTIC Science & Technology

    2009-09-01

    in inflammatory diseases (5), fibrosis (6), cancer (7,8), physiological cell migration, and pathological processes such as metastasis (9) and...implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration. Tumour Biol, 28: 123-131, 2007. 4. Müller...Verástegui, E., and Zlotnik, A. Involvement of chemokine receptors in breast cancer metastasis. Nature, 410: 50-56, 2001. 5. Khan, A., Greenman, J., and

  20. The Contribution of Genotype to Heterotopic Ossification after Orthopaedic Trauma

    DTIC Science & Technology

    2009-05-01

    have now examined 1095 patients over a two year period for HO and single nucleotide polymorphisms that may be associated with HO. Certain...all patients using the PUREGENE system (Gentra Systems Inc., Minneapolis, MN). Sixty one single nucleotide polymorphisms were examined including...lung cancer and cigarette smoke, there is also evidence of genetic predisposition to common skeletal diseases such as osteoporosis .13,14 We are

  1. The Contribution of Genotype to Heterotopic Ossification after Orthopaedic Trauma

    DTIC Science & Technology

    2010-05-01

    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...injury scores are included in ISS and both may be  associated  with ICU and  ventilator  days.   Gender was  associated  with risk with female gender actually...radiographic findings of HO in the same cohort. Statistical analyses were performed to determine associations between ISS, head AIS, ICU days, days on

  2. Severe soft tissue ossification in a southern right whale Eubalaena australis.

    PubMed

    La Sala, Luciano F; Pozzi, Luciana M; McAloose, Denise; Kaplan, Frederick S; Shore, Eileen M; Kompanje, Erwin J O; Sidor, Inga F; Musmeci, Luciana; Uhart, Marcela M

    2012-12-27

    The carcass of a stranded southern right whale Eubalaena australis, discovered on the coast of Golfo Nuevo in Península Valdés, Argentina, exhibited extensive orthotopic and heterotopic ossification, osteochondroma-like lesions, and early degenerative joint disease. Extensive soft tissue ossification led to ankylosis of the axial skeleton in a pattern that, in many respects, appeared more similar to a disabling human genetic disorder, fibrodysplasia ossificans progressiva (FOP), than to more common skeletal system diseases in cetaceans and other species. This is the first reported case of a FOP-like condition in a marine mammal and raises important questions about conserved mechanisms of orthotopic and heterotopic ossification in this clade.

  3. Severe soft tissue ossification in a southern right whale Eubalaena australis

    PubMed Central

    Sala, Luciano F. La; Pozzi, Luciana M.; McAloose, Denise; Kaplan, Frederick S.; Shore, Eileen M.; Kompanje, Erwin J. O.; Sidor, Inga F.; Musmeci, Luciana; Uhart, Marcela M.

    2013-01-01

    The carcass of a stranded southern right whale Eubalaena australis, discovered on the coast of Golfo Nuevo in Península Valdés, Argentina, exhibited extensive orthotopic and heterotopic ossification, osteochondroma-like lesions, and early degenerative joint disease. Extensive soft tissue ossification led to ankylosis of the axial skeleton in a pattern that, in many respects, appeared more similar to a disabling human genetic disorder, fibrodysplasia ossificans progressiva (FOP), than to more common skeletal system diseases in cetaceans and other species. This is the first reported case of a FOP-like condition in a marine mammal and raises important questions about conserved mechanisms of orthotopic and heterotopic ossification in this clade. PMID:23269389

  4. Diffuse pulmonary ossification: an unusual interstitial lung disease.

    PubMed

    Peros-Golubicić, Tatjana; Tekavec-Trkanjec, Jasna

    2008-09-01

    Diffuse pulmonary ossification is a rare disease characterized by diffuse small bone fragments in the lung tissue. It can be idiopathic or associated with underlying chronic pulmonary or heart diseases. The majority of cases had been diagnosed on autopsy. This review collects present knowledge of diffuse pulmonary ossification with the purpose of understanding and considering the entity in the differential diagnosis of interstitial lung diseases better. Diffuse pulmonary ossification is the result of multiple factors that interact enhancing each other. Tissue injury is the most important provoking factor that, in an alkaline environment, initiates precipitation of calcium salts, enables alkaline phosphatase activity, and activates profibrogenic cytokines. Alveolar bleeding is responsible for interstitial metallic deposition that attracts calcium salts and multinucleated giant cells. High-resolution computed tomography scan in the mediastinal window facilitates the detection of bone density lesions and provides diagnosis by using low-invasive method. Reports on the efficacy of bisphosphonates and warfarin in the management of heterotopic ossification encourage further investigation. Diffuse pulmonary ossification is still underrecognized during life. Its relevance concerning the increasing age of population and longer survival of patients with chronic diseases is underrated. A timely diagnosis will enable a better understanding of pathogenesis and natural course of disease thus paving the way to new therapeutic strategies.

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

    SciTech Connect

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

    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 on 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.

  6. Heterotopic pregnancy in HIV women

    PubMed Central

    Savasi, Valeria; Antonazzo, Patrizio; Personeni, Carlo

    2016-01-01

    Heterotopic pregnancy occurs when intrauterine and ectopic pregnancy are concomitant; overall rate rises from 1/30.000 to 1.5/1000 in assisted reproductive technology pregnancies. HIV (human immunodeficiency virus) patients are at increased risk of heterotopic pregnancies due to the greater frequency of assisted reproductive technology and pelvic inflammatory disease. We report the first case of heterotopic pregnancy in HIV woman. PMID:27928504

  7. Ossification of a rectal tumor: an uncommon finding.

    PubMed

    Smajda, Stanislas; Danse, Etienne; Mertens de Wilmars, Maud; Humblet, Yves; Kartheuser, Alex; Jouret-Mourin, Anne

    2015-12-01

    The authors report the case of a 29-year-old woman with partially calcified stage cT4N2M0 mucoid adenocarcinoma of the mid-rectum. Concomitant neoadjuvant chemoradiotherapy was administered. Preoperative CT scan and MRI demonstrated stable disease with a marked increase of its mineralized component. Histology confirmed a mucoid adenocarcinoma with ossified matrix. Osteocytes were identified in the tumor. TNM (5th edition) staging was ypT3N2M1. This case illustrates heterotopic ossification of a rectal tumor, a fairly uncommon finding. The mechanism of heterotopic bone formation within gastrointestinal adenocarcinoma has not been fully elucidated. The impact of this particular feature on patient outcome is unknown. © Acta Gastro-Enterologica Belgica.

  8. Heterotopic Pregnancy Following Reversal of Tubal Ligation.

    PubMed

    Eschenbach, Stephanie; Entzian, Dirk; Baumgarten, Deborah A

    2008-01-01

    We describe the case of a 37-year-old woman who had undergone reversal of tubal ligation with subsequent heterotopic pregnancy. We review the initial radiological evaluation of heterotopic pregnancies and the subsequent radiologic findings following appropriate therapy.

  9. Matrix remodeling during endochondral ossification.

    PubMed

    Ortega, Nathalie; Behonick, Danielle J; Werb, Zena

    2004-02-01

    Endochondral ossification, the process by which most of the skeleton is formed, is a powerful system for studying various aspects of the biological response to degraded extracellular matrix (ECM). In addition, the dependence of endochondral ossification upon neovascularization and continuous ECM remodeling provides a good model for studying the role of the matrix metalloproteases (MMPs) not only as simple effectors of ECM degradation but also as regulators of active signal-inducers for the initiation of endochondral ossification. The daunting task of elucidating their specific role during endochondral ossification has been facilitated by the development of mice deficient for various members of this family. Here, we discuss the ECM and its remodeling as one level of molecular regulation for the process of endochondral ossification, with special attention to the MMPs.

  10. Ossification of abdominal scar tissue: a case series with a translational review on its development.

    PubMed

    Fennema, E M; de Boer, J; Mastboom, W J

    2014-01-01

    Bone formation in abdominal scar tissue is a form of heterotopic ossification. It is a rare and underreported phenomenon following abdominal surgery. Heterotopic ossification (HO) is the formation of bone where normally no bone is present and two theories on its pathogenesis prevail: (1) physical dislocation of small bony fragments from the xyphoid process or os pubis into the wound, (2) differentiation of locally available multipotent mesenchymal stromal cells into osteoblasts resulting in the calcification of extracellular matrix. Multipotent mesenchymal stromal cells can differentiate into different cell types by exposing them to different stimuli. We hypothesize that pro-osteogenic signals derived from e.g., macrophages steers multipotent mesenchymal stromal cells involved in the wound healing towards osteogenesis. In a retrospective case study we analyzed ossified tissue, patient demographics, medical history, number of laparotomies, scar location, indication for surgery and time in which HO occurred. Ten (8 male, 2 female) patients had proven HO. The mean age was 62 (46-80) years. The mean time for HO to occur was 99 (24-382) days after the previous laparotomy. The mean number of relaparotomies was 3 (1-9). We conclude that ossification of abdominal scar tissue is a rare but innocent finding and provides interesting leads to other fields of research.

  11. Occipital ossification of balaenopteroid mysticetes.

    PubMed

    Walsh, Breda M; Berta, Annalisa

    2011-03-01

    The bones of the posterior portion of the mammalian skull often exhibit incomplete ossification of the joints between the bones at the time of birth, with complete ossification at some point after birth. The sequence of ossification of these joints in mysticetes can be used to characterize the relative age in the calf and early juvenile ontogenetic stages. This study examined occipital joints ossification of 38 dry prepared neonate specimens in four mysticete species from two families (Eschrichtiidae: Eschrichtius robustus; Balaenopteridae: Balaenoptera acutorostrata, Balaenoptera physalus, and Megaptera novaeangliae). Each of the joints responsible for the fusion of the occiput were examined and rated for degree of ossification. The cranial ossification analysis indicates that E. robustus calves have open occipital joints until ~6 months of age and are born at a less mature stage than closely related balaenopterids. All of the species followed the same sequence of ossification: basioccipital/exoccipital joint, followed by the basioccipital/basisphenoid joint, and completed by the supraoccipital/exoccipital joint.

  12. Heterotopic Gastric Mucosa in the Umbilicus

    PubMed Central

    Heo, Young Soo; Jeong, Se Yeong; Son, Sang Wook; Kim, Il-Hwan

    2010-01-01

    Heterotopia refers to the finding of normal tissue in foreign sites, entirely separate from the main organ. Heterotopic gastric mucosa has been observed throughout the alimentary tract, everywhere from the oral cavity to the rectum. However, occurrences in the umbilicus are an extremely rare and peculiar phenomena. We report the case of heterotopic gastric mucosa in the umbilicus. PMID:20548921

  13. Penile ossification: A reconstructive challenge.

    PubMed

    Satyanarayan, Arthi; Singla, Nirmish; Morey, Allen F

    2017-01-01

    Penile ossification is a rare condition that occurs most commonly in acquired cases of penile deformity. We report the case of a 43-year-old man with Peyronie disease who was incidentally found to have significant ossified tissue in his penile corpora during complex placement of an inflatable penile prosthesis (IPP). His clinical course was later complicated by impending distal extrusion of his IPP laterally, necessitating corporoplasty. Penile ossification remains a poorly understood, unusual entity that may pose a reconstructive challenge for urologists. We discuss evaluation and management of this condition, focusing on important considerations for preoperative counseling and intraoperative pearls.

  14. Penile ossification: A reconstructive challenge

    PubMed Central

    Satyanarayan, Arthi; Singla, Nirmish; Morey, Allen F.

    2017-01-01

    Penile ossification is a rare condition that occurs most commonly in acquired cases of penile deformity. We report the case of a 43-year-old man with Peyronie disease who was incidentally found to have significant ossified tissue in his penile corpora during complex placement of an inflatable penile prosthesis (IPP). His clinical course was later complicated by impending distal extrusion of his IPP laterally, necessitating corporoplasty. Penile ossification remains a poorly understood, unusual entity that may pose a reconstructive challenge for urologists. We discuss evaluation and management of this condition, focusing on important considerations for preoperative counseling and intraoperative pearls. PMID:28522935

  15. Ossification sequence heterochrony among amphibians.

    PubMed

    Harrington, Sean M; Harrison, Luke B; Sheil, Christopher A

    2013-01-01

    Heterochrony is an important mechanism in the evolution of amphibians. Although studies have centered on the relationship between size and shape and the rates of development, ossification sequence heterochrony also may have been important. Rigorous, phylogenetic methods for assessing sequence heterochrony are relatively new, and a comprehensive study of the relative timing of ossification of skeletal elements has not been used to identify instances of sequence heterochrony across Amphibia. In this study, a new version of the program Parsimov-based genetic inference (PGi) was used to identify shifts in ossification sequences across all extant orders of amphibians, for all major structural units of the skeleton. PGi identified a number of heterochronic sequence shifts in all analyses, the most interesting of which seem to be tied to differences in metamorphic patterns among major clades. Early ossification of the vomer, premaxilla, and dentary is retained by Apateon caducus and members of Gymnophiona and Urodela, which lack the strongly biphasic development seen in anurans. In contrast, bones associated with the jaws and face were identified as shifting late in the ancestor of Anura. The bones that do not shift late, and thereby occupy the earliest positions in the anuran cranial sequence, are those in regions of the skull that undergo the least restructuring throughout anuran metamorphosis. Additionally, within Anura, bones of the hind limb and pelvic girdle were also identified as shifting early in the sequence of ossification, which may be a result of functional constraints imposed by the drastic metamorphosis of most anurans. © 2013 Wiley Periodicals, Inc.

  16. Ossification of thoracic ligamenta flava

    SciTech Connect

    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 20-40 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.

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

    DTIC Science & Technology

    2015-07-01

    Acinetobacter baumannii, crush injury, amputation, inflammation, wound healing OVERALL PROJECT SUMMARY Task1: Bacteria inoculation dose-finding...bloc resection of the femur and surrounding musculature for histologic analysis. Bacteria Culture Conditions: Acinetobacter baumannii (strain 5075...Figure 2). There was no significant difference shown in this measure when comparing Acinetobacter with surgical controls not inoculated with bacteria

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

    DTIC Science & Technology

    2015-12-01

    plan and improve wound healing prognoses. 15. SUBJECT TERMS None listed 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...present with acute, traumatic wounds resulting from blasts, high speed projectiles, or intense burns. These injuries exhibit complicated healing ...warning of possible wound failure and provide additional information that will refine the treatment plan and improve wound healing prognoses

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

    DTIC Science & Technology

    2015-12-01

    pathogens of periodontitis .120 Several reports cited that these implants were colonized with puta- tive periodontal pathogens, including...history of periodontitis has been reported to be four- to fivefold higher than that of individuals with no histology of periodontitis ,124 thereby...a history of chronic periodontitis : a 10-year prospective cohort study of the ITI Dental Implant System. Clin Oral Implants Res. 2003;14(3): 329

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

    DTIC Science & Technology

    2016-12-01

    increased β–sheet/ disordered protein secondary structure, and increased Amide I bandwidth and shift to higher frequency of the underlying band center. Raman...with a sharp osteotome. The minced pieces were processed, and the non-adherent cells were removed by mechanical dissociation . This fraction of cells is...trabecular surface. The MS fraction is discarded. Cells that remained adherent to the trabecular surface were then dissociated by enzymatic digestion with

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

    DTIC Science & Technology

    2016-12-01

    band and decreased CH2CH2 wag bands both indicative of decreased helical and increased β–sheet/ disordered protein secondary structure, and increased...mm3) with a sharp osteotome. The minced pieces were processed, and the non-adherent cells were removed by mechanical dissociation . This fraction of...the trabecular surface. The MS fraction is discarded. Cells that remained adherent to the trabecular surface were then dissociated by enzymatic

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

    DTIC Science & Technology

    2016-12-01

    disordered protein secondary structure, and increased Amide I bandwidth and shift to higher frequency of the underlying band center. Raman detected...and the non-adherent cells were removed by mechanical dissociation . This fraction of cells is referred to as the “Marrow Space” (MS) fraction. It...remained adherent to the trabecular surface were then dissociated by enzymatic digestion with 111U/mL collagenase type I/24U/mL dispase (Worthington

  3. Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification

    DTIC Science & Technology

    2015-03-01

    titration of OPG for inhibition of RANKL-induced osteoclast formation by RAW264.7 cells. TRAP stain (violet) for osteoclast formation. Multinuclear...caALK2 HO model (Figures 2A & B and Figures 3A & B). We have adopted a sensitive passive range-of-motion assay based on one presented by Paul Yu2...orthotopic bone), were stained for the osteoclast marker tartrate-resistant acid phosphatase (TRAP) (Figure 4

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

    DTIC Science & Technology

    2013-10-01

    ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 11 19b...1a (CXCl3) chemokine (C- C motif) ligand 3 MMP9 matrix metallopeptidase 9 MYOD1 myogenic differentiation 1 NOTCH1 notch 1 OCN osteocalcin OCT4 ...gene family, member A RUNX2 (Cbfa1) runt-related transcription factor 2 SCARB1 Scavenger receptor class B member 1 SMO smoothened, frizzled family

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

    DTIC Science & Technology

    2013-10-01

    NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 6 19b. TELEPHONE NUMBER...ligand 3 MMP9 matrix metallopeptidase 9 MYOD1 myogenic differentiation 1 NOTCH1 notch 1 OCN osteocalcin OCT4 octamer-binding transcription factor 4...runt-related transcription factor 2 SCARB1 Scavenger receptor class B member 1 SMO smoothened, frizzled family receptor SMURF1 SMAD specific E3

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

    DTIC Science & Technology

    2013-10-01

    NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 11 19b. TELEPHONE NUMBER (include area code) 3...3 MMP9 matrix metallopeptidase 9 MYOD1 myogenic differentiation 1 NOTCH1 notch 1 OCN osteocalcin OCT4 octamer-binding transcription factor 4 OMD...related transcription factor 2 SCARB1 Scavenger receptor class B member 1 SMO smoothened, frizzled family receptor SMURF1 SMAD specific E3

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

    DTIC Science & Technology

    2015-10-01

    and NMRC perform Raman Spectroscopy and gene expression profiling in at-risk tissue from HO+ and HO- patients. In Year 3 team members continued...laboratory (CC). The Muschler lab performed colony analysis on these samples. Data tables with gene transcript analysis (NMRC) of biopsied wound site...imaged using phase contrast, (A,D), and stained with DAPI,(B,E) and HA, (C,F), all images 10X. 7 Gene Array (NMRC) Using a custom gene array for

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

    DTIC Science & Technology

    2015-10-01

    perform Raman Spectroscopy and gene expression profiling in at-risk tissue from HO+ and HO- patients. In Year 3 team members continued sample processing...Muschler lab performed colony analysis on these samples. Data tables with gene transcript analysis (NMRC) of biopsied wound site samples were viewed...contrast, (A,D), and stained with DAPI,(B,E) and HA, (C,F), all images 10X. 7 Gene Array (NMRC) Using a custom gene array for assessing

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

    DTIC Science & Technology

    2015-10-01

    unit performance, and the teams at WRNMMC and NMRC perform Raman Spectroscopy and gene expression profiling in at-risk tissue from HO+ and HO...wound site samples to the Muschler laboratory (CC). The Muschler lab performed colony analysis on these samples. Data tables with gene transcript...harvested by fixation, non-permeabilized and imaged using phase contrast, (A,D), and stained with DAPI,(B,E) and HA, (C,F), all images 10X. 7 Gene Array

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

    DTIC Science & Technology

    2013-04-01

    followed: Patient # Goss Photography (Fig 1) Radiographs Dehydrated PMMA Embedment Section Micro- Radiograph (Fig 1) SEM (Fig 2) Ground to...schedule since resection. 5 Figure 1: Gross photography and micro/macro radiography from one of the bone samples removed from the wounded...describe how novel technologies such as the computer assisted research environment (CAREN) may improve physical and cognitive rehabilitation for

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

    DTIC Science & Technology

    2014-10-01

    limbs following blast amputation include pain, overlying skin and muscle breakdown, poor fitting and functioning of prosthetic limbs, reoperation for...amputation revision, and impaired limb function that delays or limits rehabilitation [2-6]. Current treatments to prevent HOare limited to mitigation

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

    DTIC Science & Technology

    2014-10-01

    prosthetic ...limbs,  reoperation  for  amputation   revision,  and  impaired  limb  function  that  delays  or  limits   rehabilitation  [2... rehabilitation  /   Assoc  of  Academic  Physiatrists,  2003.  82(11):  p.  897-­‐900.  [PMID:  14566159]   5.  

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

    DTIC Science & Technology

    2014-10-01

    34 Photochemistry and Photobiology, vol. 80, pp. 98-103, 2004. 17 [9] P. V. Butte, A. N. Mamelak, M. Nuno, S. I. Bannykh, K. L. Black, and L. Marcu...34Fluorescence Lifetime Imaging of Experimental Tumors in Hematoporphyrin Derivative-Sensitized Mice," Photochemistry and Photobiology, vol. 66, pp

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

    DTIC Science & Technology

    2013-10-01

    L. Black, et al., "Fluorescence Lifetime Spectroscopy of Glioblastoma Multiforme¶," Photochemistry and Photobiology, vol. 80, pp. 98-103, 2004. [19...Taroni, and G. Valentini, "Fluorescence Lifetime Imaging of Experimental Tumors in Hematoporphyrin Derivative- Sensitized Mice," Photochemistry and

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

    DTIC Science & Technology

    2014-10-01

    the teams at WRNMMC and NMRC perform Raman Spectroscopy and gene expression profiling in at-risk tissue from HO+ and HO- patients. Year 2 work...stained biopsied samples (NMRC) were scanned (CC) and viewed for qualitative assessment and data tables with gene transcript analysis (NMRC) of biopsied...colony analysis. Gene transcript analysis has been completed from eight total biopsied sites (4 per wound), of which all (8/8) subsequently

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

    DTIC Science & Technology

    2014-10-01

    patient samples shipped from NMRC to CC. Gene Array (NMRC) A custom gene array for assessing adipogenic , chondrogenic, osteogenic, angiogenic and...tissue progenitors (CTPs) using image analysis of colony forming unit performance, and the teams at WRNMMC and NMRC perform Raman Spectroscopy and gene ...qualitative assessment and data tables with gene transcript analysis (NMRC) of biopsied wound site samples were viewed and discussed during bi-monthly

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

    DTIC Science & Technology

    2014-10-01

    tracking HO+ and HO- patient samples shipped from NMRC to CC. Gene Array (NMRC) A custom gene array for assessing adipogenic , chondrogenic...Spectroscopy and gene expression profiling in at-risk tissue from HO+ and HO- patients. Year 2 work focused on sample processing, data...and viewed for qualitative assessment and data tables with gene transcript analysis (NMRC) of biopsied wound site samples were viewed and discussed

  18. Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification

    DTIC Science & Technology

    2012-12-01

    Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send...key osteoclast formation cytokine. A second approach is by antibody inhibition of OPG, the natural antagonist of RANKL. Results from the second

  19. Defining the Balance between Regeneration and Pathological Ossification in Skeletal Muscle Following Traumatic Injury

    PubMed Central

    Davies, Owen G.; Liu, Yang; Player, Darren J.; Martin, Neil R. W.; Grover, Liam M.; Lewis, Mark P.

    2017-01-01

    Heterotopic ossification (HO) is characterized by the formation of bone at atypical sites. This type of ectopic bone formation is most prominent in skeletal muscle, most frequently resulting as a consequence of physical trauma and associated with aberrant tissue regeneration. The condition is debilitating, reducing a patient's range of motion and potentially causing severe pathologies resulting from nerve and vascular compression. Despite efforts to understand the pathological processes governing HO, there remains a lack of consensus regarding the micro-environmental conditions conducive to its formation, and attempting to define the balance between muscle regeneration and pathological ossification remains complex. The development of HO is thought to be related to a complex interplay between factors released both locally and systemically in response to trauma. It develops as skeletal muscle undergoes significant repair and regeneration, and is likely to result from the misdirected differentiation of endogenous or systemically derived progenitors in response to biochemical and/or environmental cues. The process can be sequentially delineated by the presence of inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis, chondrogenesis and ossification. However, exactly how each of these stages contributes to the formation of HO is at present not well understood. Our previous review examined the cellular contribution to HO. Therefore, the principal aim of this review will be to comprehensively outline changes in the local tissue micro-environment following trauma, and identify how these changes can alter the balance between skeletal muscle regeneration and ectopic ossification. An understanding of the mechanisms governing this condition is required for the development and advancement of HO prophylaxis and treatment, and may even hold the key to unlocking novel methods for engineering hard tissues. PMID:28421001

  20. Penile ossification and acquired penile deviation.

    PubMed

    Vahlensieck, W K; Schaefer, H E; Westenfelder, M

    1995-01-01

    We report on 3 patients with penile deviation during erection caused by ossification in the corpora cavernosa. In each case hard plaques could be palpated. These indurations were removed through a dorsal longitudinal incision. Histologically, solid bone was demonstrable. Two patients were able to resume normal sexual intercourse, but one became impotent following postoperative cavernitis. Penile ossification is rare in man, and its etiology is unknown. It bears no relationship to the os penis normally present in many other mammals. Diagnosis is best made by palpation and X-ray examination. The treatment of choice for symptomatic ossification is surgical excision.

  1. Scintigraphic assessment of heterotopic cardiac transplants

    SciTech Connect

    Wilson, M.A.; Kahn, D.R.

    1981-01-01

    Patients receiving heterotopic (''piggyback'') cardiac transplants, when the patient's own and transplanted donor hearts are connected in parallel, present special problems in determining their relative contributions to total cardiac function. Three patients who had transplants because of intractable heart failure were studied using first pass and gated equilibrium technetium-99m-labeled blood pool scintigraphy. In one patient, thallium-201 myocardial perfusion scans were obtained. These nuclear cardiology techniques provided anatomic and functional information noninvasively that proved helpful in patient management.

  2. Scintigraphic assessment of heterotopic cardiac transplants

    SciTech Connect

    Wilson, M.A.; Kahn, D.R.

    1981-10-01

    Patients receiving heterotopic (piggyback) cardiac transplants, when the patient's own and transplanted donor hearts are connected in parallel, present special problems in determining their relative contributions to total cardiac function. Three patients who had transplants because of intractable heart failure were studied using first pass and gated equilibrium technetium-99m-labeled blood pool scintigraphy. In one patient, thallium-201 myocardial perfusion scans were obtained. These nuclearcardiology techniques provided anatomic and functional information noninvasively that proved helpful in patient management.

  3. Multimodality imaging of early heterotopic bone formation.

    PubMed

    Laurin, N R; Powe, J E; Pavlosky, W F; Driedger, A A

    1990-04-01

    An atypical heterotopic bone formation that was difficult to diagnose presented in a young paraplegic patient as an acute deep vein thrombosis. A number of imaging methods, including contrast venography, ultrasonography, conventional radiography, bone scanning, leukocyte scanning, computed tomography, and magnetic resonance imaging, were used to arrive eventually at the final diagnosis. Early bone scanning remains a sensitive and effective method of diagnosis. Computed tomography can be useful in difficult cases, but the role of other imaging studies appears limited.

  4. Cornual heterotopic pregnancy: contemporary management options.

    PubMed

    Habana, A; Dokras, A; Giraldo, J L; Jones, E E

    2000-05-01

    This review covers the clinical presentations, treatments, and outcomes of cornual heterotopic pregnancies reported in the literature. Infertile women with a history of ectopic pregnancy, tubal surgery, or disease are at increased risk for cornual heterotopic pregnancy when they undergo in vitro fertilization. Women who have undergone bilateral salpingectomy also seem to be predisposed to this condition when they undergo in vitro fertilization. We recommend that these patients be followed up closely after a successful in vitro fertilization cycle with monitoring of serum beta-human chorionic gonadotropin levels and serial transvaginal ultrasonography because of the high associated morbidity. Laparotomy remains the treatment of choice for rupture of a cornual heterotopic pregnancy. In the absence of cornual rupture, however, medical management is an option that eliminates the risk of surgery and anesthesia and results in outcomes similar to those associated with surgical treatment. Currently there is insufficient evidence to recommend any single treatment modality, and the decision should be based on such factors as clinical presentation, surgeon's expertise, side effects, overall cost, and the patient's preference.

  5. [Idiopathic pulmonary hemosiderosis with dendriform pulmonary ossification].

    PubMed

    Barrera, Ana Madeleine; Vargas, Leslie

    2016-12-01

    Pulmonary ossification is a rare and usually asymptomatic finding reported as incidental in lung biopsies. Similarly, idiopathic pulmonary hemosiderosis is a rare cause of pulmonary infiltrates. We report the case of a 64-year old man with chronic respiratory symptoms in whom these two histopathological findings converged.

  6. Heterotopic Auxiliary Liver Transplantation With Portal Flow

    PubMed Central

    Lorente, Laureano; Aller, Maria Angeles; Ispizua, José Ignacio; Rodriguez, José; Durán, Hipólito

    1990-01-01

    One of the causes of auxiliary liver transplantation failure is the inter-liver competition between the host liver and the graft for the hepatotrophic factors of the portal blood. We have developed an experimental model of heterotopic partial (30%) liver isotransplant using Wistar rats so as to study this competition. Splenoportography and dissection demonstrate the existence of collateral circulation. The collaterals at 90 days post-transplant (PT) consisted of veins from the portal vein to the host liver (PR), paraesophageal veins (PE) and splenorenal veins (SR). At 60 days P.T., PR and SR veins but not PE ones appeared, and at 30 days P.T., there were only PR veins. Graft atrophy at 90 days P.T. was associated with a severe degree of bile duct proliferation. The gradual development of portal hypertension causes porto-systemic collateral circulation and the graft loses the portal hepatotrophic factors. The late development of the portal hypertension and the biliary proliferation could be caused by the hepatic arterial ischemia in this experimental model. Thus, as has been described in the orthotopic liver tansplantation, the heterotopic one might require a double vascularization, both portal and arterial. PMID:2278927

  7. AB 92. Diffuse pulmonary ossification: case report

    PubMed Central

    Baliaka, Aggeliki; Papaemmanouil, Maria; Konoglou, Maria; Zarogoulidis, Paul; Mantzarakis, Ioannis; Sakkas, Leonidas

    2012-01-01

    Background Diffuse pulmonary ossification is a rare abnormal finding characterized by the formation of mature bone tissue both in the interstitium and in the cells, with or without evidence of bone marrow. May be idiopathic or associated with chronic pulmonary, cardiac or systemic diseases. Men are affected more often than the women, usually between the sixth and eighth decade of life. They described two histologic types of pulmonary ossification: the perigraptos nodular (nodular) type and 2) dendritic (dendriform) guy. The purpose of this paper is to present an event with diffuse pulmonary ossification in a better understanding of the entity and membership in the differential diagnosis of interstitial lung disease. Patients and methods This man, 68 year old former smoker with a history of coronary heart disease, hypertension, chronic bronchitis, which was referred to the Cardiac Clinic G.N.TH. “C. Smear “because persistent pneumothorax. Under investigation, computed tomography (CT) chest revealed multiple bilateral cysts sizeable gaseous, multiple nodules in the lower lobes ypoupezokotika lung and presence of pneumothorax in the left hemithorax. Mini left thoracotomy was performed and received bioptic material. Results Histological examination showed lung parenchyma with the presence of multiple cystic formations with fibrin in the wall and a reduction of the pulmonary parenchyma. In several places there ossified tissue with presence myelochoron and bone marrow cells in afton. I diagnosis was entered: lung parenchyma with the presence emfysimatikon cysts and foci of ossification. Conclusions Diffuse pulmonary ossification remains underdiagnosed during life. Most cases are an incidental finding at autopsy, and that the absence of symptoms. An early diagnosis will allow for better treatment of the natural course of the disease, while paving the way for new therapeutic strategies.

  8. 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

  9. Heterotopic pancreas in excluded stomach diagnosed after gastric bypass surgery.

    PubMed

    Guimarães, Marta; Rodrigues, Pedro; Gonçalves, Gil; Nora, Mário; Monteiro, Mariana P

    2013-11-23

    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. 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. 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.

  10. 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

  11. Heterotopic pancreas presenting as suspicious mass in the gallbladder.

    PubMed

    Foucault, Amélie; Veilleux, Hubert; Martel, Guillaume; Lapointe, Réal; Vandenbroucke-Menu, Franck

    2012-11-10

    Heterotopic pancreas is a rare entity. Thirty-three cases in the gallbladder have been reported. We describe the first case of heterotopic pancreas mimicking a gallbladder cancer, identified within a calcified lesion in the thickened posterior wall of the gallbladder. A 72-year-old woman with right upper quadrant pain was referred with a suspicion of gallbladder neoplasia. A CT scan demonstrated a 1 cm thickened posterior wall of the gallbladder with a 2 mm punctate calcification. An open cholecystectomy was carried out without complication. The frozen section demonstrated pancreatic tissue. Heterotopic pancreas of the gallbladder is highly uncommon. It can mimic a neoplastic process in the gallbladder, particularly in the context of calcification. Its malignant potential in the gallbladder is unknown, in contrast to previously described neoplastic transformation with gastric heterotopic pancreas.

  12. Chronic epidural hematoma with rapid ossification.

    PubMed

    Chang, Jong Hee; Choi, Jae Young; Chang, Jin Woo; Park, Yong Gou; Kim, Tai Seung; Chung, Sang Sup

    2002-12-01

    The authors present a rare case of ossified chronic epidural hematoma. A 13-year-old female patient presented with an ossified chronic epidural hematoma. She had sustained a head injury about 10 weeks previously and had received conservative care for a delayed-onset epidural hematoma at a local hospital. Ossification was identified about 4 weeks after the head injury and then progressed rapidly. A chronic epidural hematoma with a thick collagenous capsule and newly formed bone was removed 73 days after the head injury. An epidural hematoma with mild symptoms can be treated conservatively. When, however, the hematoma is observed not to be naturally absorbed during serial follow-up examinations, surgical removal must be considered, even if the patient's condition is good, because this entity carries the risk of bone calcification and ossification.

  13. Uncommon Cause of Trigeminal Neuralgia: Tentorial Ossification over Trigeminal Notch

    PubMed Central

    Bang, Sun Woo; Han, Kyung Ream; Kim, Seung Ho; Jeong, Won Ho; Kim, Eun Jin; Choi, Jin Wook; Kim, Chan

    2015-01-01

    Ossification of the tentorium cerebelli over the trigeminal notch is rare, but it may cause compression of the trigeminal nerve, leading to trigeminal neuralgia (TN). We were unable to find any previously reported cases with radiological evaluation, although we did find one case with surgically proven ossification of the tentorium cerebelli. Here, we present a case of TN caused by tentorial ossification over the trigeminal notch depicted on magnetic resonance imaging (MRI) and computed tomography (CT). PMID:26380124

  14. Heterotopic autotransplantation of ovarian cortex in cynomolgus monkeys.

    PubMed

    Igarashi, Suguru; Suzuki, Nao; Hashimoto, Shu; Takae, Seido; Takenoshita, Makoto; Hosoi, Yoshihiko; Morimoto, Yoshiharu; Ishizuka, Bunpei

    2010-02-01

    Abstract In recent years, removal of ova or ovaries before chemotherapy or radiation therapy has been investigated in young female cancer patients to avoid the adverse effects of treatment. Orthotopic autotransplantation of ovarian cortex has advantages such as easy collection of ova and the possibility of spontaneous pregnancy. Although children have been born after successful orthotopic autotransplantation into the residual ovaries, some patients cannot undergo this procedure such as those who need bilateral ovariectomy or pelvic radiation therapy, therefore it is still necessary to investigate suitable heterotopic autotransplantation sites. The present study was performed in primates (cynomolgus monkeys) with the objective of determining the optimum site for heterotopic autotransplantation of ovarian cortex to enhance the clinical application of this method. The retroperitoneal iliac fossa and omentum were selected as sites for heterotopic autotransplantation. Two cynomolgus monkeys were subjected to laparotomy under anesthesia. After resection of the bilateral adnexae, the ovaries were cut into 0.5 cm cubes that were transplanted. Blood levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were monitored, and monkeys with a regular estrus cycle underwent superovulation and egg collection. In both monkeys studied, recovery of a regular estrus cycle was confirmed after heterotopic autotransplantation of ovarian tissue. MII phase ova were successfully collected from tissues transplanted into the retroperitoneal iliac fossa or omentum. Development to the early blastocyst stage was confirmed after microfertilization. We established an appropriate method of heterotopic autotransplantation using ovarian cortex into the retroperitoneal iliac fossa or omentum in primates.

  15. Orthotopic and heterotopic lower leg reimplantation. Evaluation of seven patients.

    PubMed

    Daigeler, A; Fansa, H; Schneider, W

    2003-05-01

    Reimplantation is a well-established procedure in reconstructive surgery. This is especially so after amputation of the upper limb since prostheses provide limited function. In unilateral amputation of the lower leg orthotopic reimplantation is the treatment of choice. With bilateral amputation, in which orthotopic reimplantation is not possible because of the complexity of the trauma, heterotopic reimplantation is an option. We report five patients who received orthotopic and two who received heterotopic reimplantations of the lower leg. We assessed the functional outcomewith reference to cutaneous sensation, mobility, pain, and the cosmetic result. The functional outcome was good, as was the patients' satisfaction. Their mobility, stability, and psychological state were satisfactory. Patients with heterotopic reimplantations preferred the reimplanted leg to a prosthesis. Although reimplantation of the lower leg requires prolonged hospitalisation, delayed mobilisation and secondary operations, we conclude that there is an indication for this operation in order to improve the patient's quality of life.

  16. Hypovolemic shock following induced abortion and spontaneous heterotopic pregnancy.

    PubMed

    Pakniyat, Abdolghader; Yazdanbakhsh, Arash; Moshar-Mowahed, Ghasem; Talebi, Fatimah

    2015-12-01

    Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extrauterine pregnancies occur at the same time. It is rare, estimated to occur in 1 in 30,000 pregnancies. The case was a 38-year-old woman with spontaneously conceived heterotopic pregnancy. She was admitted to our center with hypovolemic shock. Focused assessment sonography for trauma examination in emergency department showed large amount of free fluid in peritoneal cavity. She was managed surgical laparotomy. Considering spontaneous pregnancies, physician should be aware of the possibility of heterotopic pregnancy in all reproductive age women, especially those with history of recent abortion. It can occur without any predisposing risk factors. Patients should be informed about possible side effects of nonprescription medicines, and also the health care centers must be safe peaceful environment for them without severe legal consequences.

  17. Prevention of heterotopic bone formation after total hip arthroplasty: a prospective randomised study comparing postoperative radiation therapy with indomethacin medication.

    PubMed

    Kienapfel, H; Koller, M; Wüst, A; Sprey, C; Merte, H; Engenhart-Cabillic, R; Griss, P

    1999-01-01

    Heterotopic ossification (HO) after total hip arthroplasty is known to be a major complication with an impact on the functional outcome. Efforts have been made to prevent the occurrence of HO by means of either radiation therapy or pharmacotherapy. To date, there are no data available regarding the relative benefit of radiation versus medication with non-steroidal anti-inflammatory drugs. The objective of this study was to compare single-dose 600-cGy radiation therapy with indomethacin medication for their effect on the prevention of heterotopic bone formation after total hip arthroplasty. In all, 154 patients were included in the study. All patients underwent primary total hip arthroplasty due to osteoarthritis. Patients were randomly assigned to three different therapeutic groups. (a) The radiation group received a single radiation dose of 600 cGy between the 2nd and 4th postoperative day. (b) The indomethacin group received an oral application of indomethacin 2 x 50 mg per day from the 1st to 42nd postoperative day. (c) The control group received neither radiation nor indomethacin medication. There were significant group differences (P < 0.001). A least significant difference test (LSD) revealed that the mean of the control group was significantly different from that of the radiation and indomethacin groups. The 13 patients (8.4%) classified Brooker 3 or 4 were all in the control group. Again, this effect was statistically significant (chi-square, P < 0.001). In conclusion, this study demonstrated that both radiation and indomethacin therapy are effective in the prevention of postoperative HO. The choice for either one of the treatments has to be based on availability, contraindications, side-effects, practicability, standardisation and cost. Based on these considerations together with the results of this study, we currently use postoperative radiation with 600 cGy for all patients undergoing primary total hip arthroplasty.

  18. Mechanobiology and joint conformity regulate endochondral ossification of sesamoids.

    PubMed

    Sarin, V K; Carter, D R

    2000-09-01

    Sesamoid bones form by the endochondral ossification of sesamoid cartilages. This ossification process is thought to be similar to that responsible for the formation of secondary ossific nuclei in long-bone epiphyses. Sesamoids ossify much later in development than do epiphyses, however, and bone formation within sesamoids often begins by way of multiple ossific nuclei. Endochondral growth and ossification in the formation of secondary ossific nuclei have previously been correlated with distributions of the octahedral shear and hydrostatic stresses generated in vivo within cartilage anlagen. In this study, we used two-dimensional finite element analysis to predict the distributions of octahedral shear and hydrostatic stresses in an idealized model of a sesamoid cartilage subjected to in vivo loading. We examined the influence of sesamoid joint conformity. The distribution of an osteogenic stimulus was calculated with an approach similar to that used to predict epiphyseal ossification. The results suggest that, compared with conforming joints, nonconformity between the sesamoid cartilage and its articulating surface, which arises during early development, produces higher contact pressures within the sesamoid and leads to a thicker articular cartilage layer. For a nonconforming joint surface, the results suggest that ossification is favored anywhere within a broad internal region of the sesamoid, whereas a layer at the articular surface will remain cartilaginous. These findings highlight the subtle differences between ossification processes in epiphyses and sesamoids, indicating that the mechanical stress environment in sesamoids produces a diffuse stimulus leading to the onset of ossification and that the degree of joint nonconformity may influence the thickness of the articular cartilage layer.

  19. 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

  20. Retroauricular Pleomorphic Adenoma Arising from Heterotopic Salivary Gland Tissue

    PubMed Central

    Bacaj, Patrick; Borah, Gregory

    2016-01-01

    Summary: A 38-year-old woman is described who presented with a slowly growing mass on the posterior aspect of the left ear. Excision and histopathologic evaluation revealed a pleomorphic adenoma (PA) originating from heterotopic salivary gland tissue. Many authors have presented cases of PAs originating from ceruminous glands in the external auditory canal or of so-called chondroid syringoma originating from apocrine and eccrine sweat glands. This is the only case in the recent literature of a PA originating from a heterotopic rest of salivary gland tissue in the retroauricular region. The 3 main sources of PAs, their embryologic derivation, and treatment are described. PMID:27757344

  1. Retroauricular Pleomorphic Adenoma Arising from Heterotopic Salivary Gland Tissue.

    PubMed

    Grome, Luke; Bacaj, Patrick; Borah, Gregory

    2016-09-01

    A 38-year-old woman is described who presented with a slowly growing mass on the posterior aspect of the left ear. Excision and histopathologic evaluation revealed a pleomorphic adenoma (PA) originating from heterotopic salivary gland tissue. Many authors have presented cases of PAs originating from ceruminous glands in the external auditory canal or of so-called chondroid syringoma originating from apocrine and eccrine sweat glands. This is the only case in the recent literature of a PA originating from a heterotopic rest of salivary gland tissue in the retroauricular region. The 3 main sources of PAs, their embryologic derivation, and treatment are described.

  2. Heterotopic Pancreatic Pseudocyst Radiologically Mimicking Gastrointestinal Stromal Tumor

    PubMed Central

    Sarsenov, Dauren; Tırnaksız, Mehmet Bülent; Doğrul, Ahmet Bülent; Tanas, Özlem; Gedikoglu, Gökhan; Abbasoğlu, Osman

    2015-01-01

    Heterotopic pancreas is a relatively common variant of foregut embryologic dystopia that can be described as pancreatic tissue found outside the normal anatomic location, being independent from vascular supply of normal pancreas. Having all features of pancreatic tissue except for the major duct structures, this ectopic tissue may be clinically recognized when pathologic changes take place. Inflammation, hemorrhagic or obstructive states, and eventually malignancy-related problems may become a diagnostic challenge for clinician and finally lead to consequences of misdiagnosis. In this article we will discuss a case of heterotopic pancreatic tissue located in gastric cardia, which was diagnosed preoperatively as gastrointestinal stromal tumor. PMID:25785332

  3. [Rare case giant cancerous tumor forgotten after kidney heterotopic transplantation].

    PubMed

    Tyapochkin, Y A; Zubarev, V F; Golikov, A V; Afanasyeva, T V; S Klimkin, A

    2016-08-01

    The annual number of cases of kidney transplantation in the Russian Federation varies from 900 to 1000. The generally accepted method of operation is the heterotopic allotransplantation into one of the iliac region. Proper kidney recipient are psychologically "forgotten", often completely lost sight of postoperative monitoring, especially in the long term, but may remind of itself in extraordinary cases like ours.

  4. 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.

  5. Ossification of the posterior atlantoaxial membrane associated with atlas hypoplasia

    PubMed Central

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

    2016-01-01

    Abstract Rationale: Hypoplasia with an intact posterior arch of the atlas and ossification of the posterior atlantoaxial membrane (PAAM) are individually rare. Patient concerns: The patient presented with a 6-month history of progressive weakness and paresthesia of his lower extremities. Diagnoses: Cervical myelopathy resulting from atlas hypoplasia and ossification of the posterior atlantoaxial membrane. Interventions: Laminectomy of the atlas with duroplasty. Outcomes: Preoperative symptoms were alleviated. Lessons: 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. PMID:27902623

  6. 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.

  7. 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

  8. Leptin increases growth of primary ossification centers in fetal mice.

    PubMed

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

    2009-11-01

    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.

  9. Heterotopic pancreatic tissue associated with intra- and extrahepatic choledochal cysts.

    PubMed

    Suzuki, K; Uchida, T; Nakayama, H; Ugajin, W; Inaniwa, Y; Sugitani, M; Mori, Y

    1999-08-01

    A case report of heterotopic pancreas in intra- and extrahepatic biliary tracts in a 36-year-old female who suffered from intra- and extrahepatic choledochal cysts with an anomalous pancreatobiliary duct system. Histologic examination of the resected specimen showed pancreatic tissues located along the wall of the biliary tract with choledochal cysts. The pancreatic tissue consisted of acinar cells and duct elements without Langerhans' islets; the acinar cells were positive immunohistochemically for alpha-amylase and negative for endocrine hormones. Ultrastructural study revealed zymogen granules in the acinar cells. In the present case the heterotopic exocrine pancreatic tissue seems to be etiologically related to choledochal cysts as well as to the anomalous arrangement of the pancreatobiliary duct.

  10. Hemorrhagic heterotopic pregnancy in a setting of prior tubal ligation and re-anastomosis

    PubMed Central

    Esterle, Jason; Schieda, Jill

    2015-01-01

    Heterotopic pregnancy is the occurrence of simultaneous intrauterine and extrauterine pregnancies. Heterotopic pregnancy most commonly occurs during the first trimester of pregnancy in women who have significant risk factors including assisted reproductive therapy, prior ectopic pregnancy, and prior pelvic surgery or pelvic inflammatory disease. Although rare, heterotopic pregnancy must be recognized using ultrasound so as to provide appropriate treatment to the extrauterine pregnancy with the goal of preserving the intrauterine pregnancy. The case presented describes a patient with a pathologically proven (figure 8A and 8B), surgically treated 1st trimester heterotopic pregnancy. PMID:26629296

  11. Hemorrhagic heterotopic pregnancy in a setting of prior tubal ligation and re-anastomosis.

    PubMed

    Esterle, Jason; Schieda, Jill

    2015-07-01

    Heterotopic pregnancy is the occurrence of simultaneous intrauterine and extrauterine pregnancies. Heterotopic pregnancy most commonly occurs during the first trimester of pregnancy in women who have significant risk factors including assisted reproductive therapy, prior ectopic pregnancy, and prior pelvic surgery or pelvic inflammatory disease. Although rare, heterotopic pregnancy must be recognized using ultrasound so as to provide appropriate treatment to the extrauterine pregnancy with the goal of preserving the intrauterine pregnancy. The case presented describes a patient with a pathologically proven (figure 8A and 8B), surgically treated 1st trimester heterotopic pregnancy.

  12. Development of a Vascularized Heterotopic Neonatal Rat Heart Transplantation Model.

    PubMed

    Shimada, Shogo; Del Nido, Pedro J; Friehs, Ingeborg

    2016-01-01

    Rodent adult-to-adult heterotopic heart transplantation is a well-established animal model, and the detailed surgical technique with several modifications has been previously described. In immature donor organ transplantation, however, the surgical technique needs to be revised given the smaller size and fragility of the donor graft. Here, we report our surgical technique for heterotopic abdominal (AHTx) and femoral (FHTx) neonatal rat heart transplantation based on an experience of over 300 cases. Heterotopic heart transplantation was conducted in syngeneic Lewis rats. Neonatal rats (postnatal day 2-4) served as donors. AHTx was performed by utilizing the conventional adult-to-adult transplant method with specific modifications for optimal aortotomy and venous anastomosis. In the FHTx, the donor heart was vascularized by connecting the donor's aorta and pulmonary artery to the recipient's right femoral artery and vein, respectively, in an end-to-end manner. A specifically fashioned butterfly-shaped rubber sheet was used to align the target vessels properly. The transplanted graft was visually assessed for its viability and was accepted as a technical success when the viability met specific criteria. Successfully transplanted grafts were subject to further postoperative evaluation. Forty cases (AHTx and FHTx; n = 20 each) were compared regarding perioperative parameters and outcomes. Both models were technically feasible (success rate: AHTx 75% vs. FHTx 70%) by refining the conventional heterotopic transplant technique. Injury to the fragile donor aorta and congestion of the graft due to suboptimal venous connection were predominant causes of failure, leading to refractory bleeding and poor graft viability. Although the FHTx required significantly longer operation time and graft ischemic time, the in situ graft viabilities were comparable. The FHTx provided better postoperative monitoring as it enabled daily graft palpation and better echocardiographic

  13. Intussusception caused by heterotopic pancreatic tissue in a child.

    PubMed

    Mills, Robert W; McCrudden, Kimberly; Gupta, Vineet K; Britton, Andrew; Al Qahtani, Mashael; Hasan, Rashed A

    2011-01-01

    Intussusception is the leading cause of intestinal obstruction in children and is almost invariably idiopathic. Occasionally, there is a lead point for the intussusception. Intussusception caused by heterotopic pancreas (HPT) as the lead point is exceedingly rare. We report a case of intussusception caused by HPT in a child. Clinical and pathologic features and the successful medical and surgical management of the case are discussed.

  14. Anaplastic Carcinoma Possibly Arising from a Heterotopic Pancreas.

    PubMed

    Adachi, Yasushi; Mita, Hiroaki; Takahashi, Hideaki; Akino, Kimishige; Kikuchi, Takefumi; Ishii, Yoshifumi; Endo, Takao

    2015-01-01

    Anaplastic carcinoma is a rare pancreatic cancer, and the malignant transformation of a heterotopic pancreas is also rare. We herein report a case of an elderly woman with a mass of unknown origin in the abdominal cavity. Computed tomography identified the extent of the tumor but not the organ of origin. The abdominal tumor eventually metastasized to the liver and lung. An autopsy and immunohistochemical examination revealed an anaplastic carcinoma possibly originating in an ectopic pancreas.

  15. [Surgery and electroneurophysiological evaluation for CI case with modiolus ossification].

    PubMed

    Zhang, Daoxing

    2014-08-01

    The purpose of this study is to report surgical skills for CI cases with modiolus ossification and to investigate the relation between post-operational electroneurophysilogical test result and speech recognition result. Further more, we also attempt to confirm indications for CI in this specific population. Based on temporal bone HRCT, 7 subjects were identified as modiolus ossification from 101 cases with cochlear ossification. Modiolus ossification is confirmed by CT scan if CT value in modiolus reaches or exceeds 900 HU with the exception of congenital modiolus ossification or modiolus seal off. Electroneurophysiological test was conducted intra- and pos-operationally speech tests were applied for 7 subjects. Normal impedance value was observed by intro-operational measurement in 7 subjects. EABR test was conducted and negtive response was observed in only 1 subject, while other 6 subjects were confirmed with atypical EABR waves which were observed in apical and middle turn region. Hearing threshold test (in sound field) was applied, no auditory response was recorded for the subject without EABR waveform, while hearing threshold in average for the other 6 subjects was 75 dB. Results of speech tests (Mandarin) were followed as 0 for the one without EABR wave, while 100% (simple finals test) and 30% (simple initials test) for the other 6 subjects. Optimal multichannel CI surgery that inserting and locating electrode array spirally is very frequently interrupted by ossification,which was indentified with atypical EABR wave and relative poor speech recognition results, especially in modiolus ossification case. A post-operative negative EABR response may indicate surgical failure following cochlear implantation.

  16. A potential mechanism of dural ossification in ossification of ligamentum flavum.

    PubMed

    Li, Bo; Guo, Shigong; Qiu, Guixing; Li, Wenjing; Liu, Yongsheng; Zhao, Yu

    2016-07-01

    Ossification of the ligamentum flavum (OLF) mostly occurs in the thoracic spine, leading to thoracic spinal stenosis. Surgical treatment is considered as the best option for OLF patients. When the dura mater ossifies, the difficulty of surgery and the risk of complications significantly increase. The cause of dural ossification (DO) is still unknown. Based on the existing research and clinical studies, we propose a potential mechanism of DO in OLF. Firstly, with the progression of OLF, it will compress the dura mater and even the spinal cord. Then, with flexion and extension of spine, relative movement (friction) between the ossified ligamentum flavum and compressed dura mater will lead to local inflammation, subsequently causing dural adhesion. Finally, the adhesion tissue can serve as a pathway for the transportation of osteogenic cytokines (BMP for example) from the ossified ligamentum flavum to the compressed dura mater. Dura will ossify under exposure of these osteogenic cytokines. If this hypothesis is confirmed, it will contribute to the prevention and management of DO. For progressive OLF patients, early surgical treatment before DO should be recommended.

  17. Heterotopic Vascularized Joint Transfer in Mutilating Hand Injuries.

    PubMed

    Chang, Nai-Jen; Chang, Johnny T; Hsu, Chung-Chen; Lin, Cheng-Hung; Lin, Chih-Hung; Lin, Yu-Te

    2016-03-01

    In cases of mutilating hand injuries, the primary goal is recovery of prehensile function. This is particularly true in the case of joints, which are extremely difficult to replace or reconstruct adequately when damaged. Heterotopic vascularized joint transfer is indicated when salvageable joints are available for transfer to a more functionally optimal position on the hand. Seven cases of mutilating hand injuries treated with heterotopic vascularized joint transfers from 2003 to 2012 were retrospectively identified. All patients sustained severe metacarpophalangeal joint (MPJ) or proximal interphalangeal joint (PIPJ) damage that threatened recovery of optimal hand function. All patients were men, with an average age of 34.7 years. Operative, perioperative, and postoperative details including final active range of motion were collected and analyzed. Seven joints were taken from nonsalvageable amputated digits: 4 from the amputated parts, and 3 from the proximal stumps. Five joints were transferred as free flaps requiring microvascular anastomosis, and 2 were transferred on neurovascular pedicles. One joint was lost due to vasospasm. Average active range of motion was 68.3° for homojoint transfers (MPJ to MPJ, PIPJ to PIPJ), and 35° for heterojoint transfers. All but 1 patient were able to achieve tripod pinch; the remaining patient achieved only side-to-side pinch. Heterotopic vascularized joint transfer is a useful technique to consider in cases of mutilating hand injuries. Improved recovery of prehensile function can be achieved with thoughtful design and execution, followed by proper patient education and rehabilitation.

  18. FGF9 can induce endochondral ossification in cranial mesenchyme.

    PubMed

    Govindarajan, Venkatesh; Overbeek, Paul A

    2006-02-20

    The flat bones of the skull (i.e., the frontal and parietal bones) normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone. We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF), in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm. These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of) mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification.

  19. FGF9 can induce endochondral ossification in cranial mesenchyme

    PubMed Central

    Govindarajan, Venkatesh; Overbeek, Paul A

    2006-01-01

    Background The flat bones of the skull (i.e., the frontal and parietal bones) normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone. Results We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF), in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm. Conclusion These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of) mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification. PMID:16504022

  20. [Ossification of the posterior longitudinal ligament of the lumbar spine].

    PubMed

    Albisinni, U; Chianura, G; Merlini, L; Calzolari, S; Othsuka, K; Terayama, K

    1988-05-01

    The ossification of the cervical posterior longitudinal ligament (OPLL) is widely known and studied in Japan where a roentgenological incidence of 2.06% adults affected has been found. Data concerning the ossification of the lumbar posterior longitudinal ligament are few and occasional. An epidemiological survey on lumbar OPLL was performed by the authors in Matsumoto, Japan, on a total of 792 subjects, 554 of whom over the age of 35, by means of X-ray of the lumbar spine. Ossification of the lumbar posterior longitudinal ligament was detected in 23 subjects (2.9%), with no significant difference between males (3.0%) and females (2.8). Lumbar OPLL was absent in the 238 subjects aged less than 34; it was the most prevalent after the age of 45 (5.1% in males and 4.5% in females). The ossification developed in two ways: continuous ossified layer extending over several vertebrae; circumscribed ossification of the ligament corresponding to the level of the intervertebral disk (retrodiscal type). The result of this epidemiological survey showed a roentgenological incidence of lumbar OPLL of the same magnitude than that of cervical OPLL.

  1. Heterotopic pancreas complicated by pseudocyst in the gastric wall diagnosed by endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Rocha, Haroldo Luís Oliva Gomes; Bueno, Fernanda Kistemarcker do Nascimento; Faraco, Jarbas; Assef, Maurício Saab; Araki, Osvaldo Massatoshi; Nakao, Frank; Rossini, Lucio Giovanni Bapttista

    2013-07-01

    Heterotopic pancreas is usually asymptomatic and does not change throughout the patient's life, but sometimes it can present symp-toms and complications, which are rarely discrete in the literature. We present here a case of heterotopic pancreas in the gastric wall complicated with pseudocyst, and suggest that heterotopic pancreatic pseudocyst should be included in the differential diagnosis of gastric wall cysts.

  2. Heterotopic Pancreas Complicated by Pseudocyst in the Gastric Wall Diagnosed by Endoscopic Ultrasound-Guided Fine Needle Aspiration

    PubMed Central

    Rocha, Haroldo Luís Oliva Gomes; Bueno, Fernanda Kistemarcker do Nascimento; Faraco, Jarbas; Assef, Maurício Saab; Araki, Osvaldo Massatoshi; Nakao, Frank; Rossini, Lucio Giovanni Bapttista

    2013-01-01

    Heterotopic pancreas is usually asymptomatic and does not change throughout the patient's life, but sometimes it can present symp-toms and complications, which are rarely discrete in the literature. We present here a case of heterotopic pancreas in the gastric wall complicated with pseudocyst, and suggest that heterotopic pancreatic pseudocyst should be included in the differential diagnosis of gastric wall cysts. PMID:24949386

  3. Penile ossification: A traumatic event or evolutionary throwback? Case report and review of the literature.

    PubMed

    Yilmaz, Ibrahim Edhem; Barazani, Yagil; Tareen, Basir

    2013-01-01

    Penile ossification is very rare, with only a handful of histologically confirmed reported cases. The most common condition leading to penile ossification is Peyronie's disease. Other conditions, such as gout, end-stage renal disease, diabetes mellitus, hyperparathyroidism and local trauma, have also been associated with penile ossification. We report a unique case of near-complete penile ossification of the corporal bodies with histologic confirmation on pathologic review. Our report summarizes the literature regarding this rare entity.

  4. Penile ossification: A traumatic event or evolutionary throwback? Case report and review of the literature

    PubMed Central

    Yilmaz, Ibrahim Edhem; Barazani, Yagil; Tareen, Basir

    2013-01-01

    Penile ossification is very rare, with only a handful of histologically confirmed reported cases. The most common condition leading to penile ossification is Peyronie’s disease. Other conditions, such as gout, end-stage renal disease, diabetes mellitus, hyperparathyroidism and local trauma, have also been associated with penile ossification. We report a unique case of near-complete penile ossification of the corporal bodies with histologic confirmation on pathologic review. Our report summarizes the literature regarding this rare entity. PMID:23671498

  5. [Heterotopic pancreas is a rare cause of bleeding and intestinal intussusception].

    PubMed

    Andersen, Mette Winther; Østergaard, John R; Tøtterup, Anders; Jespersen, Marie Louise; Grønbæk, Henning

    2015-01-12

    A young female had neurofibromatosis, annular pancreas and heterotopic pancreas, a combination not previously described. The tumour caused bleeding and intussusception of the distal part of the small intestine. An extensive range of examinations was initiated; however, the diagnosis was not clarified until explorative laparoscopy was performed. Heterotopic pancreas is worth considering as an infrequent cause of gastrointestinal bleeding and invagination.

  6. Dural ossification associated with ossification of ligamentum flavum in the thoracic spine: a retrospective analysis

    PubMed Central

    Li, Bo; Qiu, Guixing; Guo, Shigong; Li, Wenjing; Li, Ye; Peng, Huiming; Wang, Chu; Zhao, Yu

    2016-01-01

    Objectives To investigate the incidence, distribution and radiological characteristics of dural ossification (DO) associated with ossification of ligamentum flavum (OLF) in the thoracic spine. Design A retrospective radiographical analysis. Setting This study was conducted at a single institution in China. Participants 53 patients with OLF who underwent posterior decompression surgery between January 2011 and July 2015 in a single institution were enrolled in this study. The decompression segments were grouped according to imaging evaluation and intraoperative evidences. Outcome measures The demographic distribution, radiological data and detailed surgical records were collected. First, preoperative CT images of decompressed segments were evaluated to identify imaging signs of DO. The ‘tram tack sign’ (TTS), ‘comma sign’ and ‘bridge sign’ were considered as characteristic imaging findings of DO in OLF. 4 kinds of confusing signs (false TTS) were identified and excluded. Then detailed surgical records were reviewed to finally identify segments with DO. Results The incidence of DO in patients with OLF was 43.4%. The incidence of DO in OLF segments was 21.5%. OLF was more common in the lower thoracic spine, and more than half (53.8%) of the DO was located in T9-T12. TTS was the most common sign, but it might be misdiagnosed. After excluding 4 kinds of false TTS, the sensitivity and specificity of imaging diagnosis were 94.23% and 94.21%, respectively. Conclusions DO was relatively common in thoracic OLF, especially in T9-T12. TTS might be misdiagnosed. After excluding 4 kinds of false TTS, the accuracy of imaging diagnosis was relatively high. PMID:27998902

  7. Ossification of the posterior longitudinal ligament: a case report

    PubMed Central

    Aker, PD; O’Connor, SM; Mior, SA; Beauchemin, D

    1989-01-01

    Ossification of the posterior longitudinal ligament (OPLL) has recently been recognized as a clinical entity. It is a rare condition, having a higher incidence in the Japanese population. It is characterized by hyperplasia of cartilage cells with eventual endochondral ossification of the posterior longitudinal ligament. The radiographic signs are characteristic and consist of a linear band of ossified tissue along the posterior margin of the vertebral body. OPLL can be associated with mild to serious neurological complications due to spinal cord or nerve root compression, or it may be asymptomatic. This paper reviews the radiological, clinical and therapeutic aspects of this rare condition. ImagesFigures 1 and 2Figures 3 and 4

  8. Osteochondrosis of the accessory ossification centre of the medial malleolus.

    PubMed

    Farsetti, Pasquale; Dragoni, Massimiliano; Potenza, Vito; Caterini, Roberto

    2015-01-01

    We report a case of a painful accessory ossification centre of the medial malleolus in an 11-year-old girl who was not involved in sports activities. The patient was treated conservatively, with complete clinical and radiographic healing of the medial malleolus 6 months after the first presentation. We ruled out the uncommon pathological conditions causing chronic pain in the medial malleolus during skeletal growth, such as traction apophysitis of the medial malleolus, osteochondrosis, osteochondritis or avascular necrosis of the distal tibial epiphysis. We speculate that this painful condition may be classified as an osteochondrosis of the accessory ossification centre of the medial malleolus.

  9. Gastrointestinal Hemorrhage Secondary to Duodenal Cystic Dystrophy in Heterotopic Pancreas

    PubMed Central

    Brotons, Alicia; Pico, Maria Dolores; Sola-Vera, Javier; Sillero, Carlos; Cuesta, Amador; Oliver, Israel

    2011-01-01

    Cystic dystrophy of the duodenal wall (CDDW) is a complication of heterotopic pancreatic tissue located in the wall of the gastrointestinal tract, characterized by the presence of multiple small cysts, usually found in the wall of the second part of the duodenum. Gastrointestinal hemorrhage due to CDDW is a rare complication. We report the case of a 50-year-old man who was admitted to our hospital for persistent vomiting. The imaging tests confirmed the diagnosis of CDDW. During his stay in hospital, the patient had a gastrointestinal hemorrhage secondary to this disorder, which made it necessary to perform a Roux-en-Y gastrojejunostomy (Billroth III). PMID:27957010

  10. Multimodality Imaging Evaluation of an Uncommon Entity: Esophageal Heterotopic Pancreas

    PubMed Central

    Mack, Takman; Lowry, Debra; Carbone, Peter; Barbick, Brian; Kindelan, Joshua; Marks, Robert

    2014-01-01

    A 25-year-old male was referred to the Radiology Department with new onset of right upper quadrant and epigastric abdominal pain. He had no past medical or surgical history. Physical exam was unremarkable. The patient underwent computed tomography (CT), fluoroscopic upper gastrointestinal (GI) evaluation, endoscopic ultrasound (EUS), and positron emission tomography (PET) evaluation, revealing the presence of a heterogeneous esophageal mass. In light of imaging findings and clinical workup, the patient was ultimately referred for thorascopic surgery. Surgical findings and histology confirmed the diagnosis of esophageal heterotopic pancreas. PMID:24744946

  11. Patterns of ossification in southern versus northern placental mammals.

    PubMed

    Hautier, Lionel; Bennett, Nigel C; Viljoen, Hermien; Howard, Lauren; Milinkovitch, Michel C; Tzika, Athanasia C; Goswami, Anjali; Asher, Robert J

    2013-07-01

    Consensus on placental mammal phylogeny is fairly recent compared to that for vertebrates as a whole. A stable phylogenetic hypothesis enables investigation into the possibility that placental clades differ from one another in terms of their development. Here, we focus on the sequence of skeletal ossification as a possible source of developmental distinctiveness in "northern" (Laurasiatheria and Euarchontoglires) versus "southern" (Afrotheria and Xenarthra) placental clades. We contribute data on cranial and postcranial ossification events during growth in Afrotheria, including elephants, hyraxes, golden moles, tenrecs, sengis, and aardvarks. We use three different techniques to quantify sequence heterochrony: continuous method, sequence-ANOVA (analysis of variance) and event-paring/Parsimov. We show that afrotherians significantly differ from other placentals by an early ossification of the orbitosphenoid and caudal vertebrae. Our analysis also suggests that both southern placental groups show a greater degree of developmental variability; however, they rarely seem to vary in the same direction, especially regarding the shifts that differ statistically. The latter observation is inconsistent with the Atlantogenata hypothesis in which afrotherians are considered as the sister clade of xenarthrans. Interestingly, ancestral nodes for Laurasiatheria and Euarchontoglires show very similar trends and our results suggest that developmental homogeneity in some ossification sequences may be restricted to northern placental mammals (Boreoeutheria).

  12. 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

  13. 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…

  14. 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…

  15. Femoral neuropathy secondary to ossification of the ligamentum flavum.

    PubMed

    Debiais, F; Bataille, B; Debiais, P; Azais, I; Bontoux, D; Alcalay, M

    2000-05-01

    Radiculopathy resulting from ossification of the ligamentum flavum (OLF) is extremely rare and concerns only intercostal neuralgias. We describe a 37-year-old Caucasian woman with a lumbar radiculopathy revealing an OLF. Her symptoms were completely and definitively relieved by surgery.

  16. 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.

  17. Skeletal ossification and sequence heterochrony in xenarthran evolution.

    PubMed

    Hautier, Lionel; Weisbecker, Vera; Goswami, Anjali; Knight, Frank; Kardjilov, Nikolay; Asher, Robert J

    2011-01-01

    Previous analyses of how mammals vary in their ossification sequences have focused on monotremes, marsupials, and boreoeutherian placentals. Here, we focus on the sequence of cranial and postcranial ossification events during growth in the xenarthran skull and skeleton, including armadillos, anteaters, and sloths. We use two different methods to quantify sequence heterochrony: sequence analysis of variance (ANOVA) and event-paring/Parsimov. Our results indicate that Parsimov is conservative and does not detect clear heterochronic shifts between xenarthran and boreoeutherian placentals. Sequence-ANOVA performs better, but both methods exhibit sensitivity to the artifactual accumulation of ties. By controlling for ties and taking into account results that the methods have in common, our analysis suggests that xenarthrans significantly differ from other placentals by a late ossification of the sternum and an early ossification of the phalanges and pubis. We interpret these differences as showing that heterochrony plays a role in the skeletal development of xenarthrans, a change from previous studies that have emphasized the developmental homogeneity of the skeleton across placental mammals. © 2011 Wiley Periodicals, Inc.

  18. [Diffuse pulmonary ossification associated with idiopathic pulmonary fibrosis].

    PubMed

    Fernández Crisosto, C A; Quercia Arias, O; Bustamante, N; Moreno, H; Uribe Echevarría, A

    2004-12-01

    Diffuse pulmonary ossification is a rare entity that presents with the formation of mature bone in the pulmonary parenchyma and is associated with diffuse and chronic lung disease, heart disease, or other system disorders. Diffuse pulmonary ossification is usually a postmortem finding by the pathologist. In the case we report, the diagnosis was established by open lung biopsy. The patient was a 79-year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed tomography revealed interstitial disease predominantly in the septum with multiple cavitations that tended to form honeycomb patterns. Pleural thickening, retraction of the parenchyma, and bilateral fibrosis were also visible. A clinical diagnosis of interstitial fibrosis was established and the patient s course was unfavorable. An open lung biopsy was performed. The lung tissue specimens revealed zones with collapsed alveoli and others with emphysema, some of which produced secretion and erythrocytic extravasation. Interstitial vascular congestion was apparent; bronchioles presented mononuclear and some polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of predominantly interstitial, multicentric foci of osseous trabeculae --some of which included adipose bone marrow. Diffuse pulmonary ossification is usually an incidental finding in autopsies of patients with a history of diffuse chronic pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It is a marker of the chronicity and/or severity of the fibrosis.

  19. Monotreme ossification sequences and the riddle of mammalian skeletal development.

    PubMed

    Weisbecker, Vera

    2011-05-01

    The developmental differences between marsupials, placentals, and monotremes are thought to be reflected in differing patterns of postcranial development and diversity. However, developmental polarities remain obscured by the rarity of monotreme data. Here, I present the first postcranial ossification sequences of the monotreme echidna and platypus, and compare these with published data from other mammals and amniotes. Strikingly, monotreme stylopodia (humerus, femur) ossify after the more distal zeugopodia (radius/ulna, tibia/fibula), resembling only the European mole among all amniotes assessed. European moles also share extreme humeral adaptations to rotation digging and/or swimming with monotremes, suggesting a causal relationship between adaptation and ossification heterochrony. Late femoral ossification with respect to tibia/fibula in monotremes and moles points toward developmental integration of the serially homologous fore- and hindlimb bones. Monotreme cervical ribs and coracoids ossify later than in most amniotes but are similarly timed as homologous ossifications in therians, where they are lost as independent bones. This loss may have been facilitated by a developmental delay of coracoids and cervical ribs at the base of mammals. The monotreme sequence, although highly derived, resembles placentals more than marsupials. Thus, marsupial postcranial development, and potentially related diversity constraints, may not represent the ancestral mammalian condition.

  20. Spinal dural ossification causing neurological signs in a cat.

    PubMed

    Antila, Johanna M; Jeserevics, Janis; Rakauskas, Mindaugas; Anttila, Marjukka; Cizinauskas, Sigitas

    2013-06-19

    A six-year-old Ragdoll cat underwent examination due to a six-month history of slowly progressive gait abnormalities. The cat presented with an ambulatory tetraparesis with a neurological examination indicating a C1-T2 myelopathy. Radiographs of the spine showed a radiopaque irregular line ventrally in the vertebral canal dorsal to vertebral bodies C3-C5. In this area, magnetic resonance imaging revealed an intradural extramedullary/extradural lesion compressing the spinal cord. The spinal cord was surgically decompressed. The cause of the spinal cord compression was dural ossification, a diagnosis confirmed by histopathological examination of the surgically dissected sample of dura mater. The cat gradually improved after the procedure and was ambulating better than prior to the surgery. The cat's locomotion later worsened again due to ossified plaques in the dura causing spinal cord compression on the same cervical area as before. Oral prednisolone treatment provided temporary remission. Ten months after surgery, the cat was euthanized due to severe worsening of gait abnormalities, non-ambulatory tetraparesis. Necropsy confirmed spinal cord compression and secondary degenerative changes in the spinal cord on cervical and lumbar areas caused by dural ossification. To our knowledge, this is the first report of spinal dural ossification in a cat. The reported cat showed neurological signs associated with these dural changes. Dural ossification should be considered in the differential diagnosis of compressive spinal cord disorders in cats.

  1. Autogenic heterotopic vascularized proximal interphalangeal joint transplantation in children.

    PubMed

    Chiu, David T W; Lee, Jonathan

    2011-03-01

    The proximal interphalangeal joint (PIP) joint is the most crucial joint for the functionality of a finger. For a child with complex injury of the hand every effort should be exercised to maximize function restoration. If the PIP joint is irreparably damaged, its reconstruction is indicated. The technique of autogenic heterotopic vascularized toe joint transplantation provides unique advantage of a composite transfer of skin, tendons, bone and joint alone with growth plate and its efficacy has been affirmed in children. It has been suggested that such transfers require intact flexor tendon to achieve satisfactory results, our experience however indicates quite the contrary. As evidenced by this report of a 7-year-old boy with abrasion and avulsion injury to his dominant right hand resulting in a complex defect with skin lose, extensor, flexor avulsion along with cominution of the PIP joint of his long finger. A surgical formulation of staged reconstruction scheme including an autogenic heterotopic vascularized toe joint transplantation led to complete functional restoration to his right hand.

  2. Heterotopic autologous chondrocyte transplantation--a realistic approach to support articular cartilage repair?

    PubMed

    El Sayed, Karym; Haisch, Andreas; John, Thilo; Marzahn, Ulrike; Lohan, Anke; Müller, Riccarda D; Kohl, Benjamin; Ertel, Wolfgang; Stoelzel, Katharina; Schulze-Tanzil, Gundula

    2010-12-01

    Injured articular cartilage is limited in its capacity to heal. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but it requires articular cartilage biopsies for sufficient autologous chondrocyte expansion in vitro. Hence, ACT is restricted by donor-site morbidity and autologous articular chondrocytes availability. The use of nonarticular heterotopic chondrocytes such as auricular, nasoseptal, or costal chondrocytes for ACT might overcome these limitations: heterotopic sources show lesser donor-site morbidity and a comparable extracellular cartilage matrix synthesis profile to articular cartilage. However, heterotopic (h)ACT poses a challenge. Particular tissue characteristics of heterotopic cartilage, divergent culturing peculiarities of heterotopic chondrocytes, and the advantages and drawbacks related to these diverse cartilage sources were critically discussed. Finally, available in vitro and in vivo experimental (h)ACT approaches were summarized. The quality of the cartilage engineered using heterotopic chondrocytes remains partly controversy due to the divergent methodologies and culture conditions used. While some encouraging in vivo results using (h)ACT have been demonstrated, standardized culturing protocols are strongly required. However, whether heterotopic chondrocytes implanted into joint cartilage defects maintain their particular tissue properties or can be adapted via tissue engineering strategies to fulfill regular articular cartilage functions requires further studies.

  3. [Spontaneous and assisted reproduction-associated heterotopic pregnancy. The clinical characteristics].

    PubMed

    Barrón Vallejo, J; Góngora Rodríguez, A; Kuttothara, A; Kably Ambe, A

    1999-07-01

    Heterotopic pregnancy is an uncommon obstetric entity with variegated symptomatology. The objective of this report is to describe the clinical findings of the two varieties of heterotopic pregnancy, spontaneous an related with Assisted Reproduction Techniques (ART). Three cases of heterotopic pregnancy are described, two spontaneous and one occurred after in vitro fertilization and embryo transfer (IVF-ET). The two former culminated in miscarriage of intrauterine pregnancy and tubal rupture; and the late obscured for the ovarian hyperstimulation syndrome which prevented accurate ultrasonographic diagnosis. The clinical presentation and key differences are discussed.

  4. 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

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

    PubMed

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

    2012-06-07

    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.

  6. Meniscal ossification. II. The normal pattern in the tiger knee.

    PubMed

    Ganey, T M; Ogden, J A; Abou-Madi, N; Colville, B; Zdyziarski, J M; Olsen, J H

    1994-04-01

    Examination of knee menisci of Bengal tigers revealed ossicles within the cartilaginous anterior horn of each medial meniscus. This ossification was not evident in the neonatal animal, but was present in animals aged 20 months or older. The ossicle appeared prior to the completion of skeletal maturation at the knee, and was composed of normal remodeling trabecular bone. While most animals had a single, variably sized ossicle, multiple ossicles also occurred. The meniscal cartilage apposed to the femoral articulation exhibited a distinct columnar pattern in the region of the ossicle, in contrast to the non-columnar pattern throughout the bulk of the meniscus, including the ossicle side apposed to the tibial plateau. In this particular large mammalian species medial meniscal ossification appears to be a normal anatomical variation that progressively develops following birth, and may serve as a model for the phylogenetic (developmental) theory of etiology.

  7. Detection of heterotopic gray matter in children by magnetic resonance imaging.

    PubMed

    Dunn, V; Mock, T; Bell, W E; Smith, W

    1986-01-01

    Heterotopic gray matter results from abnormal brain development and is a recognized focus of seizures. It may be associated with mental retardation and/or severe malformations of the brain. Three patients with heterotopia of gray matter were identified by magnetic resonance imaging (MRI). CT failed to detect the heterotopic gray matter in each case. One child was referred for removal of a neoplasm based on CT studies until MRI demonstrated the developmental nature of his condition. One infant had severely dysplastic left cerebral hemisphere associated with heterotopic gray matter and the syndrome of Hypomelanosis of Ito. All three children suffered from seizures and/or mental retardation. MRI provided important information in the management of each case and appears to be the imaging method of choice in evaluating children with seizures or retardation for heterotopic gray matter in the brain.

  8. Association of heterotopic gray matter with seizures: MR imaging. Work in progress.

    PubMed

    Smith, A S; Weinstein, M A; Quencer, R M; Muroff, L R; Stonesifer, K J; Li, F C; Wener, L; Soloman, M A; Cruse, R P; Rosenberg, L H

    1988-07-01

    Heterotopic gray matter, which previously had been associated with severe congenital malformations of the brain and developmental delay, was found without these associated conditions. The authors found ten cases of heterotopic gray matter on magnetic resonance (MR) images. The lesions had a signal intensity that was isointense compared with that of gray matter on T1, spin-density, and T2-weighted images. Nine of the ten cases were associated with a seizure disorder. The tenth case, discovered during a workup for metastatic lung disease, was confirmed with pathologic studies. Heterotopic gray matter is the presence of cortical neurons in an abnormal location, which may be periventricular (nodular) or within the white matter (laminar). A knowledge of heterotopic gray matter and its association with seizures may prevent the misinterpretation of findings on MR images.

  9. Just a mirage: heterotopic intrauterine and twin ectopic pregnancy mimicked by mirror imaging on ultrasound.

    PubMed

    Ahmed, Rimsha; Samardzic, Dejan; Santos, Michael A; Mesina, Anna; Maines, Jaimie

    2017-06-01

    Heterotopic pregnancies are rare and are usually diagnosed by transvaginal ultrasound. Despite the routine use of sonography in early pregnancy, artifact created by mirror imaging can drastically and erroneously alter medical decision making by interfering with image interpretation. A heterotopic pregnancy with a single intrauterine gestation and twin left adnexal ectopic gestational sacs was observed on ultrasound in a woman presenting with abdominal pain. During laparoscopy, an ectopic pregnancy was not identified, and subsequent intraoperative ultrasound reproduced the heterotopic pregnancy through manipulation of bowel, confirming mirror image artifact. This phenomenon is rarely seen in obstetric imaging; therefore, lack of awareness can lead to false diagnosis of heterotopic pregnancy. Techniques to verify correct diagnosis should be used to resolve potential mirror artifact before proceeding with surgical management.

  10. Bilateral and symmetrical heterotopic submandibular glands in the upper neck: case report.

    PubMed

    Sanli, Emine Ciğdem; Oztürk, Nail Can; Polat, Ayşe; Oztürk, Hakan

    2010-12-01

    During the neck dissection of a male cadaver, large heterotopic submandibular glands were encountered bilaterally in the upper neck. They were symmetrical, capsulated and lay deep to the superficial lamina of the superficial cervical fascia. Both glands were located in the submandibular and carotid triangles. The somewhat smaller orthotopic submandibular glands and the sublingual glands were in their normal anatomic location. Duct of the heterotopic gland united with the corresponding orthotopic submandibular gland's duct on each side and ended on the ipsilateral sublingual caruncle. Histopathologic examination of the heterotopic glands revealed seromucous (mainly serous) tissue. A bilaterally situated symmetrical heterotopic submandibular gland of this size has not heretofore been reported in the literature. The embryological and clinical significance of this case is discussed.

  11. Ossification of the ligamentum flavum in a Caucasian: case report.

    PubMed

    Parekh, H C; Gurusinghe, N T; Perera, S S; Prabhu, S S

    1993-01-01

    Ossification of the ligamenta flava (OLF) and posterior longitudinal ligament (OPLL) of the spine causing spinal cord compression is described mainly in Japanese patients and is often termed as 'Japanese disease'. We are reporting a case of OLF of the thoracic spine seen in a male Caucasian who presented with an intractable intercostal pain. This is the first case report of OLF in a Caucasian.

  12. Long-term survival after orthotopic and heterotopic cardiac transplantation.

    PubMed Central

    Cooper, D K; Charles, R G; Fraser, R C; Beck, W; Barnard, C N

    1980-01-01

    Five long-term survivors of heart transplantation were reinvestigated. Two patients had undergone orthotopic heart transplantation over 11 and 9 years earlier and constitute two of the world's longest-surviving patients after this procedure. Three patients had undergone heterotopic heart transplantation (one left heart bypass alone and two biventricular bypass) four to six years earlier. Four of the five patients had had only one or no documented acute rejection episodes. Three had been given blood transfusions. None had had particularly good tissue matching in relation to the donor on HLA typing. All five patients were leading full and active lives. At review two patients had significant coronary artery disease, one severe, presumably due to chronic immune-complex deposition. Heart transplantation remains a major undertaking, but it can offer the patient many years of good-quality life. Images p1095-a p1095-b PMID:7000291

  13. 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.

  14. [Heterotopic pregnancy: report of a case and review of the literature].

    PubMed

    Espinosa Picazo, M; Alcántar Mendoza, M A

    1997-11-01

    A case of spontaneous tubal heterotopic pregnancy in primigest patient with survival of intrauterine conception is presented. She was treated in H.G.Z.M.F. No. 8 IMSS in Ciudad Sahagún Hgo. The frequency antecedents, clinical picture, auxiliary methods of diagnosis and therapy are discussed. It is concluded that the heterotopic pregnancy is a rare illness, but it can occur, and is potentially dangerous to the mother and intrauterine conception. The instant detection improves the prognosis.

  15. [Pleomorphic adenoma on heterotopic salivary inclusion: case report and literature review].

    PubMed

    Papuzinski Aguayo, Cristian; Selamé Glena, Rodrigo; Bermeo Sanchez, Jaime; Lozano Burgos, Carlo

    2015-07-23

    Heterotopic salivary gland tissue is the presence of salivary tissue outside of the salivary glands. It is an uncommon condition but it can be the source of the full spectrum of salivary gland diseases. We present a rare case of pleomorphic adenoma developing from heterotopic salivary gland tissue in an upper neck lymph node not related to the major salivary glands. This article reviews the difficulty of the differential diagnosis with other cervical masses, embryogenesis, clinical manifestations and treatment of this condition.

  16. The mechanical integrity of in vivo engineered heterotopic bone.

    PubMed

    Warnke, Patrick H; Springer, Ingo N; Acil, Yahya; Julga, Gerrit; Wiltfang, Jörg; Ludwig, Klaus; Russo, Paul A J; Sherry, Eugene; Sivananthan, Sureshan; Hedderich, Jürgen; Terheyden, Hendrik

    2006-03-01

    Recent advances in tissue engineering have aroused interest in growth of heterotopic bone for the repair of skeletal defects. This study demonstrates an in vivo method in minipigs of engineering individual human-sized mandible replacements of heterotopic bone with a mechanical integrity similar to natural bone. Ten individualized mandible replacement scaffolds were created using computer-aided design (CAD) techniques. Five had a resorbable external scaffold made of polylactite mesh (test group 1) and five had had a non-resorbable external scaffold of titanium mesh (test group 2). The mesh scaffolds were loaded each with five BioOss blocks serving as internal scaffolds and 3.5 mg recombinant human Bone Morphogenetic Protein-7. The loaded mesh scaffolds were implanted into the latissimus dorsi muscles of five infant minipigs. After 6 weeks the mandible replacements were harvested. Core biopsy cylinders were taken from the replacements of both test groups and from the natural pig mandibles (control 1). Also, core biopsies from plain BioOss Blocks were gained (control 2). The core biopsy cylinders were loaded axially into a compression test device to evaluate the mechanical compression resistance. Additional specimen underwent histological examination. Both test groups resulted in successful bone induction with degrees of compression resistance [Test 1: 1.62 MPa (SD+/-0.73); Test 2: 1.51 MPa (SD+/-0.56)] statistically insignificant when compared to natural porcine mandibular bone [1.75 MPa (SD+/-0.69)]. This differed significantly from the much lower compression resistance seen in the unadulterated BioOss [0.92 MPa (SD+/-0.04)]. Following this, the in vivo engineered bone has a similar mechanical compression stability as natural bone.

  17. Calcitonin treatment for intersternocostoclavicular ossification: clinical experience in two cases.

    PubMed Central

    Misaki, T; Dokoh, S; Mori, E

    1991-01-01

    Intersternocostoclavicular ossification is a benign arthro-osteitis of the upper anterior chest of unknown cause. Two patients with acute exacerbation of this disorder were successfully treated with intramuscular injections of an eel calcitonin analogue (40 units three times a week). Besides symptomatic relief of local pain and swelling, serial scintigrams showed quantitative improvement in radiophosphonate uptake. The rapid alleviation of pain implies that the hormone has a central analgesic effect, in addition to its direct influence on bone cells and antiinflammatory action. In one patient the disease was associated with palmoplantar pustulosis, which was cured with oral colchicine, whereas the other patient did not have such skin lesions. Despite a hypothetical link between palmoplantar pustulosis and intersternocostoclavicular ossification, colchicine had no beneficial impact on the bone pain. Salmon calcitonin delivered by nasal spray was tried for the second patient but failed, probably because of insufficient drug delivery. The initial favourable results described here warrant future use of calcitonin injection on a larger number of patients with intersternocostoclavicular ossification. Images PMID:1772298

  18. Neurogenesis of heterotopic gray matter in the brain of the microcephalic mouse.

    PubMed

    Sun, X Z; Takahashi, S; Fukui, Y; Hisano, S; Kubota, Y; Sato, H; Inouye, M

    2001-12-15

    Neurogenesis of heterotopic gray matter in the brain of the microcephalic mouse prenatally exposed to X-rays at embryonic day 13 (E13) was studied immunohistochemically. Bromodeoxyuridine (BrdU) as a marker to label the migrating position of neuroblasts generated at various embryonic stages showed that no "inside-out" pattern of neuronal migration occurred in the heterotopic cell mass similar to that seen in the laminated cortex. Further results in which midkind (MK) immunoreactive radial glial fibers did not appear in the heterotopic cell mass demonstrated that heterotopia formed in the absence of radial glia system. Different types of cells (pyramidal and non-pyramidal neurons) in the heterotopic cell mass were identified with immunoreactivity for anti-parvalbumin and anti-calbindin D-28K antibodies in addition to current histological methods. Two major types of neurons were mixed together with random distribution in the heterotopic cell mass. This finding indicates that irradiation might have no selective effects on the precursors of pyramidal and non-pyramidal neurons. Moreover, anti-glial fibrillary acidic protein (GFAP) immunostaining showed that numerous astrocytes were present in the heterotopic cell mass. The fact that astrocytes appeared in the heterotopia without the transition from classic radial glial cells to astrocytes suggests that astrocytes might be generated directly from a separate astroglial precursor.

  19. 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.

  20. A Study of Ossification of Carpal and Tarsal Bones in Normal and Hypothyroid Foals

    PubMed Central

    McLaughlin, B. G.; Doige, C. E.

    1982-01-01

    The degree of ossification of carpal and tarsal bones was determined in normal foals of various ages and in hypothyroid and thyroidectomized foals. In normal foals ossification occurred very rapidly in the last few weeks of gestation and less rapidly from birth to 33 days. The ulnar carpal bone was consistently less ossified than other carpal or tarsal bones. Foals with congenital hyperplastic goitre had retarded ossification of the cuboidal bones, especially the central and third tarsal bones. Thyroidectomized foals had retarded ossification of lesser degree. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. PMID:17422143

  1. Cochlear ossification in patients with profound hearing loss following bacterial meningitis.

    PubMed

    Caye-Thomasen, Per; Dam, Mikkel Seidelin; Omland, Silje Haukali; Mantoni, Margit

    2012-07-01

    Cochlear ossification following bacterial meningitis is related to causative pathogen, but not age at disease or time point of evaluation. However, progression may occur over time, especially in case of primary signs of ossification. To investigate the occurrence and degree of cochlear ossification on CT and MRI in patients with bilateral profound hearing loss following bacterial meningitis, in relation to causative pathogen, age at disease, and time point of evaluation. Progression of ossification in cases that underwent more than one scan was evaluated. In the period 1982-2008, 47 cochlear implantations were performed in 34 consecutive candidates suffering from bilateral profound hearing loss following bacterial meningitis. A retrospective review of patient files and preoperative CT and MR images was performed. Cochlear ossification was observed in 35% of patients and 26% of ears on CT. The corresponding values for MRI were 44 and 30% (difference not significant). Streptococcus pneumoniae infection caused ossification more frequently than Neisseria meningitidis. No difference was found between pediatric and adult cases, and the occurrence of ossification was not related to the time point of evaluation. Signs of progressive ossification were found in cases with two CT scans, especially if ossification was present at the first scan.

  2. Heterotopic Heart Transplantation in Three Patients at the Texas Heart Institute

    PubMed Central

    Frazier, O. Howard; Okereke, John; Cooley, Denton A.; Radovancevic, Branislav; Chandler, Linda B.; Powers, Penny

    1985-01-01

    Seventy-three orthotopic and three heterotopic transplantations have been done in our institution, and in this report, we describe the procedure and outcome of those who underwent heterotopic transplantation. Three patients were in critical condition while awaiting donors for heart transplantation, and in each case, a suitable donor could not be found. Smaller donor hearts became available, and knowing that these patients would die without some kind of immediate action, we performed heterotopic heart transplantations. Patient Number 1 was a 53-year-old diabetic man who was in the last stages of heart disease when a small donor heart became available. Because of his rapidly deteriorating condition, we did a heterotopic transplantation. The patient is presently well and functioning normally. Patient Number 2 was a 26-year-old woman who received the heart of a 13-year-old donor after it became obvious that she could not wait for a suitable donor. We performed a heterotopic transplantation, after which the patient continues to function well. Patient Number 3 was a 53-year-old man who weighed 260 lbs. When a suitable donor could not be found, the heart of a 170-lb man became available and was used in a heterotopic transplantation. This patient also continues to be active and well. After considering the various advantages and disadvantages of heterotopic transplantation, we are convinced that there is a definite place for this procedure in some patients with end-stage cardiac failure, although we still believe that orthotopic transplantation should be offered to most recipients. Images PMID:15227008

  3. The development of centres of ossification of bones forming elbow joints in young swine.

    PubMed

    Visco, D M; Hill, M A; Van Sickle, D C; Kincaid, S A

    1990-08-01

    Epiphyseal centres of ossification in the bones forming the elbow joints of pigs between one day and 15 weeks of age were examined radiographically, macroscopically, mesoscopically and microscopically. Thoracic limbs from 39 pigs were perfused with India ink or silicone rubber injection compound and the bones were dissected free of soft tissues. The humerus, ulna and radius were fixed in formalin or ethyl alcohol and then cleared by the modified Spalteholz technique. Bones were radiographed, examined grossly, and then cut into slabs for mesoscopical evaluation. Foci considered to be calcifying within cartilaginous anlage were selected for microscopical examination. It was concluded that the epiphyseal centre of ossification develops at different times in different sites in the bones forming the elbow joint. Centres of ossification are initiated when foci of chondrocytes adjacent to one side of a cartilage canal undergo hypertrophy and the inter-territorial matrix becomes calcified. Osteogenesis then proceeds in the calcified focus, presumably with osteoprogenitor cells that originate within the cartilage canals. Subsequently, each epiphyseal centre of ossification enlarges by one of two methods. Firstly, the layer of cartilage adjacent to the centre undergoes endochondral ossification, thus allowing for the circumferential growth of the epiphyseal centre of ossification. Secondly, foci of calcification develop adjacent to the ends of cartilage canals near the epiphyseal centre of ossification and eventually the focus of calcification coalesces with the developing epiphyseal centre of ossification, thus establishing a new ossification front. Endochondral ossification continues at the periphery of the mass of bone. Mesoscopical examination is more useful than radiographical evaluation for identifying small foci of calcification which precede epiphyseal centres of ossification.

  4. The development of centres of ossification of bones forming elbow joints in young swine.

    PubMed Central

    Visco, D M; Hill, M A; Van Sickle, D C; Kincaid, S A

    1990-01-01

    Epiphyseal centres of ossification in the bones forming the elbow joints of pigs between one day and 15 weeks of age were examined radiographically, macroscopically, mesoscopically and microscopically. Thoracic limbs from 39 pigs were perfused with India ink or silicone rubber injection compound and the bones were dissected free of soft tissues. The humerus, ulna and radius were fixed in formalin or ethyl alcohol and then cleared by the modified Spalteholz technique. Bones were radiographed, examined grossly, and then cut into slabs for mesoscopical evaluation. Foci considered to be calcifying within cartilaginous anlage were selected for microscopical examination. It was concluded that the epiphyseal centre of ossification develops at different times in different sites in the bones forming the elbow joint. Centres of ossification are initiated when foci of chondrocytes adjacent to one side of a cartilage canal undergo hypertrophy and the inter-territorial matrix becomes calcified. Osteogenesis then proceeds in the calcified focus, presumably with osteoprogenitor cells that originate within the cartilage canals. Subsequently, each epiphyseal centre of ossification enlarges by one of two methods. Firstly, the layer of cartilage adjacent to the centre undergoes endochondral ossification, thus allowing for the circumferential growth of the epiphyseal centre of ossification. Secondly, foci of calcification develop adjacent to the ends of cartilage canals near the epiphyseal centre of ossification and eventually the focus of calcification coalesces with the developing epiphyseal centre of ossification, thus establishing a new ossification front. Endochondral ossification continues at the periphery of the mass of bone. Mesoscopical examination is more useful than radiographical evaluation for identifying small foci of calcification which precede epiphyseal centres of ossification. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:2081708

  5. [Endometrial ossification: a report of four cases and literature review].

    PubMed

    Nevarez Bernal, Roberto; Vilchis Nava, Pablo; Kably Ambe, Alberto

    2007-03-01

    Endometrial ossification is a rare endometrial pathology. Its predisposing factors include history of uterine curettage to metabolic abnormalities. It usually presents in patients with secondary infertility and history of first trimester pregnancy loss, accompanied by severe dysmenorrhea and dyspareunia. The diagnosis is suspected by OB-GYN history and USG findings, therapeutic strategies range from D&C to hysterectomy, we propose diagnosis and management by hysteroscopy in order to preserve future fertility and minimize uterine damage. A review of four cases during 1985-2004 from a large assisted reproduction center in Mexico City is presented.

  6. Protective effect of Cissus quadrangularis Linn. on diabetes induced delayed fetal skeletal ossification.

    PubMed

    Sirasanagandla, Srinivasa Rao; Ranganath Pai, K Sreedhara; Potu, Bhagath Kumar; Bhat, Kumar Mr

    2014-01-01

    Delayed fetal skeletal ossification is one of the known complications of maternal diabetes. The present study was designed to evaluate the protective role of petroleum ether extract of Cissus quadrangularis (PECQ) on diabetes-induced delayed fetal skeletal ossification. Female Wistar rats were rendered diabetic with streptozotocin (STZ, 40 mg/kg, intraperitonial) before mating. After confirmation of pregnancy, the pregnant rats were divided into three groups: normal control group, diabetic control group, and diabetic + CQ group. The diabetic + CQ group pregnant rats were treated with PECQ (500 mg/kg body weight) throughout their gestation period. Immediately after delivery, pups were collected from all three groups and processed for alizarin red S-alcian blue staining in order to examine the pattern of skeletal ossification. Fewer ossification centers and decreased extent of ossification of forelimb and hindlimb bones were observed in the neonatal pups of diabetic control group as compared to those in the normal control group. PECQ pretreatment significantly restored the ossification centers and improved the extent of ossification of forelimb and hindlimb bones in the neonatal pups of diabetic + CQ group as compared to those in the diabetic control group. The results suggested that PECQ treatment is effective against diabetes-induced delayed fetal skeletal ossification. However, further studies on the isolation and characterization of active constituents of PECQ, which can cross the placental barrier and are responsible for the bone anabolic activity are warranted.

  7. Ossification heterochrony in the therian postcranial skeleton and the marsupial-placental dichotomy.

    PubMed

    Weisbecker, Vera; Goswami, Anjali; Wroe, Stephen; Sánchez-Villagra, Marcelo R

    2008-08-01

    Postcranial ossification sequences in 24 therian mammals and three outgroup taxa were obtained using clear staining and computed tomography to test the hypothesis that the marsupial forelimb is developmentally accelerated, and to assess patterns of therian postcranial ossification. Sequence rank variation of individual bones, phylogenetic analysis, and algorithm-based heterochrony optimization using event pairs were employed. Phylogenetic analysis only recovers Marsupialia, Australidelphia, and Eulipotyphla. Little heterochrony is found within marsupials and placentals. However, heterochrony was observed between marsupials and placentals, relating to late ossification in hind limb long bones and early ossification of the anterior axial skeleton. Also, ossification rank position of marsupial forelimb and shoulder girdle elements is more conservative than that of placentals; in placentals the hind limb area is more conservative. The differing ossification patterns in marsupials can be explained with a combination of muscular strain and energy allocation constraints, both resulting from the requirement of active movement of the altricial marsupial neonates toward the teat. Peramelemorphs, which are comparatively passive at birth and include species with relatively derived forelimbs, differ little from other marsupials in ossification sequence. This suggests that ossification heterochrony in marsupials is not directly related to diversity constraints on the marsupial forelimb and shoulder girdle.

  8. Ossification of the vertebral column in human foetuses: histological and computed tomography studies.

    PubMed

    Skórzewska, A; Grzymisławska, M; Bruska, M; Lupicka, J; Woźniak, W

    2013-08-01

    There is no agreement in the literature as to the time of the onset and progress of the vertebral column ossification. The aim of the present study was to determine the precise sequence of ossification of the neural arches and vertebral centra.Histological and radiographic studies were performed on 27 human foetuses aged from 9 to 21 weeks. It was found that the ossification of vertebrae commences in foetuses aged 10 and 11 weeks. Ossification centres appear first for neuralarches in the cervical and upper thoracic vertebrae and by the end of 11th week they are present in all thoracic and lumbar neural arches. In the vertebral centrain foetus of 10 weeks ossification was found in the lower 7 thoracic and first lumbar vertebrae. By the end of 11th week ossification is present in the lower 4 cervical, all thoracic, all lumbar and 4 sacral vertebral centra. The study indicates that ossification of the neural arches proceeds in the craniocaudal direction,whereas in the vertebral centra it progresses from the lower thoracic vertebrae into both directions. Different shapes of ossification centres were also described.

  9. Protective effect of Cissus quadrangularis Linn. on diabetes induced delayed fetal skeletal ossification

    PubMed Central

    Sirasanagandla, Srinivasa Rao; Ranganath Pai, K. Sreedhara; Potu, Bhagath Kumar; Bhat, Kumar MR

    2014-01-01

    Background: Delayed fetal skeletal ossification is one of the known complications of maternal diabetes. Objective: The present study was designed to evaluate the protective role of petroleum ether extract of Cissus quadrangularis (PECQ) on diabetes-induced delayed fetal skeletal ossification. Materials and Methods: Female Wistar rats were rendered diabetic with streptozotocin (STZ, 40 mg/kg, intraperitonial) before mating. After confirmation of pregnancy, the pregnant rats were divided into three groups: normal control group, diabetic control group, and diabetic + CQ group. The diabetic + CQ group pregnant rats were treated with PECQ (500 mg/kg body weight) throughout their gestation period. Immediately after delivery, pups were collected from all three groups and processed for alizarin red S–alcian blue staining in order to examine the pattern of skeletal ossification. Results: Fewer ossification centers and decreased extent of ossification of forelimb and hindlimb bones were observed in the neonatal pups of diabetic control group as compared to those in the normal control group. PECQ pretreatment significantly restored the ossification centers and improved the extent of ossification of forelimb and hindlimb bones in the neonatal pups of diabetic + CQ group as compared to those in the diabetic control group. Conclusions: The results suggested that PECQ treatment is effective against diabetes-induced delayed fetal skeletal ossification. However, further studies on the isolation and characterization of active constituents of PECQ, which can cross the placental barrier and are responsible for the bone anabolic activity are warranted. PMID:24812472

  10. Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic gray matter.

    PubMed

    Chen, Huan-Xin; Roper, Steven N

    2003-01-01

    Neuronal heterotopia has a strong association with epilepsy, but the mechanisms that underlie this relationship are largely unknown. We have utilized the in utero irradiated rat model to study circuit abnormalities in experimentally induced subcortical heterotopic gray matter. Spontaneous and miniature inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents were recorded from visualized heterotopic pyramidal neurons in in vitro hemispheric slices and compared with control neocortical pyramidal neurons using the whole cell patch-clamp technique. The frequency of spontaneous and miniature IPSCs was significantly reduced in pyramidal neurons from heterotopic cortex. Amplitude and kinetics of IPSCs were not different between the two groups. Spontaneous and miniature EPSCs were not different between the two groups. Short-term synaptic plasticity of stimulus-evoked EPSCs showed depression in heterotopic neurons and facilitation in control pyramidal neurons. This study shows a selective impairment of the GABAergic circuitry in experimental heterotopic gray matter. We have reported similar findings in normotopic dysplastic cortex from this model. Taken together, these studies demonstrate a pervasive defect in inhibition throughout the cortex of irradiated rats with cortical dysplasia and neuronal heterotopia. This may have important implications regarding cortical development and function following in utero injuries.

  11. [Primary heterotopic pleural hydatid cyst presenting as a pneumothorax].

    PubMed

    Marghli, A; Ayadi-Kaddour, A; Ouerghi, S; Boudaya, M S; Zairi, S; Smati, B; Mestiri, T; Kilani, T

    2011-03-01

    Hydatid cyst is a parasitic disease that is endemic in many countries. Pneumothorax may be a presentation of this disease that presents urgent problems of diagnosis and treatment. We report the case of a 23-year-old woman, amenorrheic for 22 weeks, who presented with chest pain and dyspnoea. Chest x-ray revealed a right-sided tension pneumothorax. A check x-ray after drainage showed a homogeneous opacity of water density occupying the lower 2/3 of the right hemithorax. Thoracic ultrasound suggested an uncomplicated hydatid cyst at the right base. Surgical exploration revealed a hydatid cyst 14cm in diameter in the pleural space, and a cavity in the right lower lobe with two bronchial fistulae. Treatment consisted of removal of the cyst intact, closure of the bronchial fistulae and capitonnage of the residual cavity. The postoperative course was uncomplicated. Primary heterotopic pleural hydatid cyst is an exceptional cause of pneumothorax that should considered in countries where hydatid disease is endemic. Treatment is surgical following drainage of the pneumothorax. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  12. An Extraperitoneal Technique for Murine Heterotopic Cardiac Transplantation.

    PubMed

    Nowocin, A K; Brown, K; Edwards, L A; Meader, L; Hill, J I; Wong, W

    2015-09-01

    The mouse heterotopic cardiac transplantation model has been used extensively by investigators in the field of organ transplantation to study the rejection process, test new antirejection treatments, tolerance induction protocols or to understand basic immunological principles. Due to its extensive use, any small refinement of the technique would have a major impact on replacement, reduction and refinement (commonly known as the 3Rs). Here, we describe a novel approach to refine this model. The donor aorta and pulmonary artery are anastomosed peripherally to the femoral artery and vein of the recipient, respectively. The technical success rate is comparable to the conventional abdominal site, but it avoids a laparotomy and handling of the bowels making it less invasive method. As a result, recipients recover faster and require less postoperative analgesia. It is a major refinement under one of the 3Rs and would represent an advance in animal welfare in scientific research. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Heterotopic Transcallosal Projections Are Present throughout the Mouse Cortex

    PubMed Central

    Chovsepian, Alexandra; Empl, Laura; Correa, Daphne; Bareyre, Florence M.

    2017-01-01

    Transcallosal projection neurons are a population of pyramidal excitatory neurons located in layers II/III and to a lesser extent layer V of the cortex. Their axons form the corpus callosum thereby providing an inter-hemispheric connection in the brain. While transcallosal projection neurons have been described in some detail before, it is so far unclear whether they are uniformly organized throughout the cortex or whether different functional regions of the cortex contain distinct adaptations of their transcallosal connectivity. To address this question, we have therefore conducted a systematic analysis of transcallosal projection neurons and their axons across six distinct stereotactic coordinates in the mouse cortex that cover different areas of the motor and somatosensory cortices. Using anterograde and retrograde tracing techniques, we found that in agreement with previous studies, most of the transcallosal projections show a precise homotopic organization. The somata of these neurons are predominantly located in layer II/III and layer V but notably smaller numbers of these cells are also found in layer IV and layer VI. In addition, regional differences in the distribution of their somata and the precision of their projections exist indicating that while transcallosal neurons show a uniform organization throughout the mouse cortex, there is a sizeable fraction of these connections that are heterotopic. Our study thus provides a comprehensive characterization of transcallosal connectivity in different cortical areas that can serve as the basis for further investigations of the establishment of inter-hemispheric projections in development and their alterations in disease. PMID:28270750

  14. Estimation of fetal age from dimensions of atlas and axis ossification centers.

    PubMed

    Castellana, C; Kósa, F

    2001-03-01

    The atlas and axis ossification centers of 106 human fetal and neonate skeletons were measured. The skeletons belong to the collection in the Department of Forensic Medicine of the Albert Szent-Györgyi Medical University, Szeged, Hungary. The age of the skeletons ranged from 4 to 10 lunar months. Nine linear measurements on the atlas, seven on the axis neural arches ossification centers and three on each one of the axis centra ossification centers were taken. We did simple and multiple linear regression analysis to estimate the age of fetuses. The results show that it is possible to use regression equations to estimate the fetal body length and age from atlas and axis ossification centers measurements during the whole period of development studied. The study of size and shape of the ossification centers using factorial analysis (principal component analysis) shows that the shape of the dens of the axis might be useful to estimate fetal viability.

  15. Pathogenesis of ligaments ossification in spondyloarthritis: insights and doubts.

    PubMed

    Neve, Anna; Maruotti, Nicola; Corrado, Addolorata; Cantatore, Francesco Paolo

    2017-05-01

    Despite intensive research in spondyloarthritis pathogenesis, some important questions still remain unanswered, particularly concerning enthesis new bone formation. Several evidences suggest that it prevalently occurs by endochondral ossification, however it remains to identify factors that can induce and influence its initiation and progression. Recent progress, achieved in animal models and in vitro and genetic association studies, has led us to hypothesize that several systemic factors (adipokines and gut hormones) and local factors (BMP and Wnt signaling) as well as angiogenesis and mechanical stress are involved. We critically review and summarize the available data and delineate the possible mechanisms involved in enthesis ossification, particularly at spinal ligament level. KEY MESSAGES Complete understanding of spondyloarthritis pathophysiology requires insights into inflammation, bone destruction and bone formation, which are all located in entheses and lead all together to ankylosis and functional disability. Several factors probably play a role in the pathogenesis of bone formation in entheses including not only cytokines but also several systemic factors such as adipokines and gut hormones, and local factors, such as BMP and Wnt signaling, as well as angiogenesis and mechanical stress. Data available about pathophysiology of new bone formation in spondyloarthritis are limited and often conflicting and future studies are needed to better delineate it and to develop new therapeutic approaches.

  16. 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.

  17. Histology of epiphyseal cartilage calcification and endochondral ossification.

    PubMed

    Amizuka, Norio; Hasegawa, Tomoka; Oda, Kimimitsu; Luiz de Freitas, Paulo Henrique; Hoshi, Kazuto; Li, Minqi; Ozawa, Hidehiro

    2012-01-01

    Cartilage calcification is carried out by chondrocytes as they hypertrophy and begin to secrete matrix vesicles. Calcification initiates when calcium phosphates appear inside these matrix vesicles, forming hydroxyapatite crystals that eventually break through the membrane to form calcifying globules, as in bone calcification. However, the extracellular environment in cartilage is different from that in bone: cartilage is abundant in proteoglycans but contains a small amount of osteopontin. Hypertrophic chondrocytes secrete vesicles in the cartilaginous matrix of intercolumnar septae only, forming well-calcified longitudinal septae and poorly-calcified transverse partitions. Such pattern of vesicle deposition permits the invasion of endothelial cells, which infiltrate into cartilage and induce migration of osteogenic and osteoclastic cells. Osteoclasts resorb the excess of calcified globules in the partitions, shaping calcified cartilage cores paralleling the longitudinal axis of long bones. After the formation of these calcified cartilage cores, endochondral ossification involves a series of well-defined events in which osteogenic cells deposit new bone onto the cartilage core and form primary trabecules. This review presents the histology of epiphyseal cartilage calcification and endochondral ossification.

  18. Synaptic responses of neurons in heterotopic gray matter in an animal model of cortical dysgenesis.

    PubMed

    Smith, B N; Dudek, F E; Roper, S N

    1999-11-01

    Neuronal heterotopia is a malformation of cortical development that is closely associated with epilepsy in humans. Despite emerging interest in the structure and function of the heterotopic cortex, little is known about the membrane properties and synaptic connections of these displaced neurons. We used whole-cell patch-clamp and extracellular field potential recordings from heterotopic neurons in slices from young adult rats with experimentally induced cortical dysgenesis to determine if local synaptic connections were present in nodular heterotopia. Complex synaptic responses were observed after electrical stimulation of adjacent white matter. The results suggest that neurons in nodular heterotopic gray matter can form local excitatory and inhibitory synaptic connections and may participate in epileptiform events.

  19. [Heterotopic pregnancy with intrauterine dizygotic twins following embryo transfer in the blastocyst phase].

    PubMed

    Barrón Vallejo, J; Ortega Díaz, R; Kably Ambe, A

    1999-04-01

    Ectopic pregnancy is a common complication of in vitro fertilization and embryo transfer (IVF-ET). On other hand, heterotopic pregnancy complicates 1-2% of all IVF-ET pregnancies. Tubal damage as reason for treatment and multiple embryo transfer might predispose patients to this complication. We present a successful treated case of an infertile patient that developed simultaneous twin intra- and single extra- uterine pregnancy after blastocyst-stage embryo transfer. In IVF-ET patients presence of an intrauterine gestation not exclude the possibility of a concomitant extrauterine pregnancy. Awareness of the possibility of heterotopic pregnancy after IVF-ET plays an important role in the successful treatment of this reproductive complication. Transfer of good quality embryos can be a risk factor to develop heterotopic pregnancy.

  20. PGA-associated heterotopic chondrocyte cocultures: implications of nasoseptal and auricular chondrocytes in articular cartilage repair.

    PubMed

    El Sayed, K; Marzahn, U; John, T; Hoyer, M; Zreiqat, H; Witthuhn, A; Kohl, B; Haisch, A; Schulze-Tanzil, G

    2013-01-01

    The availability of autologous articular chondrocytes remains a limiting issue in matrix assisted autologous chondrocyte transplantation. Non-articular heterotopic chondrocytes could be an alternative autologous cell source. The aims of this study were to establish heterotopic chondrocyte cocultures to analyze cell-cell compatibilities and to characterize the chondrogenic potential of nasoseptal chondrocytes compared to articular chondrocytes. Primary porcine and human nasoseptal and articular chondrocytes were investigated for extracellular cartilage matrix (ECM) expression in a monolayer culture. 3D polyglycolic acid- (PGA) associated porcine heterotopic mono- and cocultures were assessed for cell vitality, types II, I, and total collagen-, and proteoglycan content. The type II collagen, lubricin, and Sox9 gene expressions were significantly higher in articular compared with nasoseptal monolayer chondrocytes, while type IX collagen expression was lower in articular chondrocytes. Only β1-integrin gene expression was significantly inferior in humans but not in porcine nasoseptal compared with articular chondrocytes, indicating species-dependent differences. Heterotopic chondrocytes in PGA cultures revealed high vitality with proteoglycan-rich hyaline-like ECM production. Similar amounts of type II collagen deposition and type II/I collagen ratios were found in heterotopic chondrocytes cultured on PGA compared to articular chondrocytes. Quantitative analyses revealed a time-dependent increase in total collagen and proteoglycan content, whereby the differences between heterotopic and articular chondrocyte cultures were not significant. Nasoseptal and auricular chondrocytes monocultured in PGA or cocultured with articular chondrocytes revealed a comparable high chondrogenic potential in a tissue engineering setting, which created the opportunity to test them in vivo for articular cartilage repair. Copyright © 2011 John Wiley & Sons, Ltd.

  1. Increased Prevalence of Ossification of Posterior Longitudinal Ligament and Increased Bone Mineral Density in Patients with Ossification of Nuchal Ligament

    PubMed Central

    Kim, Ki-Wan; Eun, Jong-Pil

    2016-01-01

    Objective There are also few studies demonstrating the relationship between ossification of nuchal ligament (ONL) and ossification of posterior longitudinal ligament (OPLL). We compared the prevalence, location, and type of OPLL between patients with ONL and matched patients without ONL.We also compared the bone mineral densities (BMDs) between the 2 groups. Methods total of 124 cervical ONL patients were enrolled in this study. The control group of 124 patients was matched with 124 patients with ONL by age and sex on a 1:1 basis to minimize confounding factors. We reviewed the prevalence, location, and type of OPLL in both groups. Results The prevalence of OPLL was almost 2.5 times greater in patients with ONL than those without ONL. The mean value of BMD in patients with ONL was greater at the lumbar spine (L1-L4) than in patients without ONL. The mean T score of the lumbar spine was 0.25±1.68 in the patients with ONL and -0.73±1.64 in the patients without ONL. Conclusion The prevalence of OPLL in patients with ONL was significantly higher than in patients without ONL. Because ONL is innocuous and may be seen more readily than OPLL on simple cervical radiographs, clinicians should consider the possibility of coexisting OPLL when ONL, especially extensive ONL, is detected in patients with neck pain, radiculopathy, or myelopathy, to facilitate proper treatment. PMID:27799994

  2. A potential method for identifying dural ossification by measuring the degree of spinal stenosis in thoracic ossification of ligamentum flavum.

    PubMed

    Li, Bo; Qiu, Guixing; Zhao, Yu

    2016-11-01

    Ossification of ligamentum flavum (OLF) is increasingly recognized as the major cause of thoracic spinal stenosis. The dura mater beneath ossified ligamentum flavum may also ossify when the spinal stenosis develops to a certain degree. Preoperative diagnosis of dural ossification (DO) is beneficial for surgical management of OLF. However, currently, accurate diagnosis method still could not be obtained. Based on the association between spinal stenosis and OLF/DO, a potential diagnosis method is proposed in this paper: identifying DO by measuring the degree of spinal stenosis in thoracic OLF. In the early stage of OLF, there is only mild spinal stenosis and no DO. With the progression of OLF, dura may also ossify and further compress the spinal cord, aggravating spinal stenosis. Before DO, the dura mater is presented as a low signal intensity. Once ossifying, the dura mater will be shown as a high signal intensity in CT. It will lead that the degree of spinal stenosis measured in axial CT scan obviously increases. Thus, it provides a possibility to find a critical value of it for distinguishing OLF patients with or without DO. Copyright © 2016. Published by Elsevier Ltd.

  3. [Submucosal gastric tumour: heterotopic pancreas. A case report and review of the literature].

    PubMed

    Esquivel, Carlos; Ballario, Federico; García, Sebastián; Giraudo, Pedro; Esteban Granero, Lucas

    2011-09-01

    Heterotopic pancreas is the presence of pancreatic tissue outside the anatomical location of the pancreas. It is a rare condition and can occur anywhere in the gastrointestinal tract with the stomach and small bowel as the most common sites. It is usually asymptomatic but may become clinically evident when complicates by pathologic changes such as inflammation, bleeding, obstruction and malignant transformation. We report the case of a 49-year-old man who presented with recurrent epigastric pain. The upper gastrointestinal endoscopy revealed a submucosal tumour in the antrum. The histopathology study after surgery showed a heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of a submucosal gastric tumour.

  4. Prognostic Value of the Radiologic Appearance of the Navicular Ossification Center in Congenital Talipes Equinovarus.

    PubMed

    Atanda, Abiola A; Oni, Julius K; Ramsden, David M; Yoon, Richard S; Ahmad, Alaa A; Otsuka, Norman Y

    2015-01-01

    Congenital talipes equinovarus (CTEV), more commonly known as clubfoot, is a deformity of the foot that is not well understood. The tarsal navicular is at the center of the disease process and exhibits abnormal development and delayed ossification. However, its role in the pathologic process is not clear. The aim of the present study was to better understand the role of the tarsal navicular in CTEV by correlating the presence of the navicular ossification center and relapse of clubfoot deformity after surgical treatment. The medical records and radiographs of 34 patients (41 feet) with surgically treated CTEV were reviewed for the presence of the navicular ossification center and the lateral talocalcaneal angles. Of the 41 feet, 17 (41.46%) did not have the tarsal navicular ossification center present before surgery, and 24 (58.54%) did have the ossification center present. The talocalcaneal angles were similar between those with and without the navicular ossification center present. No significant difference was found in the incidence of relapse between the nonossified navicular group (17.6%) and the ossified navicular group (16.7%; p = .63). The presence of the navicular ossification center before surgery does not appear to have prognostic value for the relapse of CTEV after surgical intervention.

  5. Relationships between fetal body weight of Wistar rats at term and the extent of skeletal ossification.

    PubMed

    Chahoud, I; Paumgartten, F J R

    2005-04-01

    We investigated the relationship between fetal body weight at term (pregnancy day 21) and the extent of ossification of sternum, metacarpus, metatarsus, phalanges (proximal, medial and distal) of fore- and hindlimbs and cervical and coccygeal vertebrae in Wistar rats. The relationships between fetal body weight and sex, intrauterine position, uterine horn, horn size, and litter size were determined using historical control data (7594 fetuses; 769 litters) of untreated rats. Relationships between body weight and degree of ossification were examined in a subset of 1484 historical control fetuses (154 litters) which were subsequently cleared and stained with alizarin red S. Fetal weight was independent of horn size, uterine horn side (left or right) or intrauterine position. Males were heavier than females and fetal weight decreased with increasing litter size. Evaluation of the skeleton showed that ossification of sternum, metacarpus and metatarsus was extensively complete and independent of fetal weight on pregnancy day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight. The strongest correlation between body weight and degree of ossification was found for hindlimb, medial and proximal phalanges. Our data therefore suggest that, in full-term rat fetuses (day 21), reduced ossification of sternum, metacarpus and metatarsus results from a localized impairment of bone calcification (i.e., a malformation or variation) rather than from general growth retardation and that ossification of hindlimb (medial and proximal) phalanges is a good indicator of treatment-induced fetal growth retardation.

  6. Ossification of the femur and tibia of the post-hatching Japanese quail.

    PubMed

    Ahmed, Yasser A; Soliman, Soha A; Abdel-Hafez, Enas A

    2013-09-01

    The current study aimed to describe the histological changes of the femur and tibia of the post-hatching quail. Femur and tibia from 1-day- to 6-weeks post-hatching quail were processed for light microscopy. Histological examination revealed that endochondral ossification was a delayed process in the development of femur and tibia preceded by periosteal ossification. Femur and tibia of 1-day-post-hatching quail consisted of growth cartilage enclosed in a tube of periosteal bone collar. The collar extended toward the epiphysis dividing it into articular cartilage proper and lateral articular cartilage. Down to the articular cartilage, there was a physeal growth cartilage, in which the chondrocytes were organized into resting, proliferative and hypertrophic zones. Focal areas of hypertrophic chondrocytes were observed in the epiphysis of the tibia but not of the femur, which acted as a nidus for formation of the secondary ossification centre after in 2-week-posthathcing quail. Primary ossification centre was seen in both femur and tibia after 2 weeks and ossification continued replacing the cartilage until the 6th week when only permanent articular cartilage remained. Cartilage canals were present in both femur and tibia starting from the day 1, but chondrified and completely disappeared after the 6th week. The current study suggests that the periosteal ossification preceded the endochondral ossification and plays an important role in quail long bones development.

  7. MR Imaging of the Pituitary Gland and Postsphenoid Ossification in Fetal Specimens.

    PubMed

    Mehemed, T M; Fushimi, Y; Okada, T; Kanagaki, M; Yamamoto, A; Okada, T; Takakuwa, T; Yamada, S; Togashi, K

    2016-08-01

    A thorough knowledge of fetal growth and development is key to understanding both the normal and abnormal fetal MR imaging findings. We investigated the size and signal intensity of the normal pituitary gland and the intrasphenoidal ossification around the Rathke pouch in formalin-fixed fetuses on MR imaging. Thirty-two fetuses with undamaged brains were included in this study (mean age, 19.93 weeks; age range, 12-31 weeks). Visual inspection of the pituitary and ossification around the Rathke pouch in the sphenoid bone or the postsphenoid ossification was conducted. The extent of pituitary and postsphenoid ossification, pituitary/pons signal ratio, and postsphenoidal ossification/sphenoid bone signal ratio was compared according to gestational age. The pituitary gland was identified as a hyperintense intrasellar structure in all cases, and postsphenoid ossification was identified as an intrasphenoidal hyperintense area in 27 of the 32 cases (84%). The mean pituitary/pons signal ratio was 1.13 ± 0.18 and correlated weakly with gestational age (R(2) = 0.243), while the mean postsphenoid ossification/sphenoid bone signal ratio was 2.14 ± 0.56 and did not show any increase with gestational age (R(2) = 0.05). No apparent change in the size of pituitary hyperintensity was seen with gestational age (R(2) = 0.001). Postsphenoid ossification showed an increase in size with gestational age (R(2) = 0.307). The fetal pituitary gland was hyperintense on T1-weighted images and the pituitary/pons ratio and extent of postsphenoid ossification correlated weakly with gestational age. © 2016 by American Journal of Neuroradiology.

  8. The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

    PubMed Central

    Yan, Liang; Gao, Rui; Liu, Yang; He, Baorong; Lv, Shemin; Hao, Dingjun

    2017-01-01

    Ossification of the posterior longitudinal ligament (OPLL) is a multi-factorial disease involving an ectopic bone formation of spinal ligaments. It affects 0.8-3.0% aging Asian and 0.1-1.7% aging European Caucasian. The ossified ligament compresses nerve roots in the spinal cord and causes serious neurological problems such as myelopathy and radiculopathy. Research in understanding pathogenesis of OPLL over the past several decades have revealed many genetic and non-genetic factors contributing to the development and progress of OPLL. The characterizations of aberrant signaling of bone morphogenetic protein (BMP) and mitogen-activated protein kinases (MAPK), and the pathological phenotypes of OPLL-derived mesenchymal stem cells (MSCs) have provided new insights on the molecular mechanisms underlying OPLL. This paper reviews the recent progress in understanding the pathophysiology of OPLL and proposes future research directions on OPLL. PMID:28966802

  9. Extra Ossification Center at the Tip of the Medial Malleolus Suspected as Fracture: A Clinical Clue.

    PubMed

    Aydın, Deniz

    2016-01-01

    The appearance of displaced bone inferior (distal) to the medial malleolus, present on radiographs in an adolescent patient, can be confused with a fracture, when, in fact, it is the radiographic appearance of a secondary center of ossification. Foot and ankle surgeons should be aware of extra ossification centers and accessory bones, including one at the tip of the medial malleolus, to avoid misdiagnosis and overtreatment. In the present report, I describe the case of a 9-year-old male with bilateral extra ossification centers at the tip of each medial malleolus. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Effect of arsenic in endochondral ossification of experimental animals.

    PubMed

    Aybar Odstrcil, Ana del Carmen; Carino, Silvia Norma; Ricci, Juan Carlos Diaz; Mandalunis, Patricia Mónica

    2010-05-01

    Arsenic (As) toxicity is a global health problem affecting millions of people, the most toxic forms being Arsenites [As(III)] and Arsenates [As(V)]. Arsenic intoxication can occur through different exposure routes. The aim of the present work was to determine the effect of As on endochondral ossification and bone remodeling in experimental animals, by means of biochemical, histologic, and histomorphometric determinations. Sixteen male Wistar rats, 100g body weight (b.w.), were divided into two groups: experimental group (n=8), treated with 10mg/l of NaAsO(2) in their drinking water, receiving 0.21mg/kgb.w./day during 45 days; and control group (n=8) remained untreated. On day 45, blood samples were obtained by cardiac puncture to perform hematologic blood counts and biochemical determination. The animals were killed, the tibiae, femurs, kidneys and livers were resected, fixed in formalin and processed histologically. Tibia and femur sections were obtained and stained with H&E. The following histomorphometric parameters were determined on tibia and femur sections: bone volume (BV/TV), thickness of growth plate cartilage (GPC.Th) and thickness of hypertrophic zone (HpZ.Th). Biochemical determinations showed that experimental animals exhibited neutrophilia and a decrease in lymphocytes and monocytes. As levels were below 1 microg/dl in both groups. The femur sections of the experimental group showed (1) a statistically significant increase in total growth cartilage plate thickness (p<0.05) at the expense of the hypertrophic zone (p<0.05); (2) subchondral trabecular bone sealed to the growth plate with a non-significant increase in primary spongiosa bone volume. These results suggest that As alters endochondral ossification.

  11. Acute abdominal pain following fracture of a heterotopically formed bone incorporating a prolene mesh.

    PubMed

    Nageswaran, H; Dunkley, A

    2010-09-01

    A case is presented of severe abdominal pain around a healed scar following fracture of a heterotopically formed bone. This should be considered an unusual differential diagnosis in patients with acute pain of unknown origin who had open abdominal surgery in the past. To our knowledge, we have also reported the first case of hetertopic bone formation incorporating a prolene mesh.

  12. Intussusception caused by heterotopic gastric mucosa in small intestine: a case report.

    PubMed

    Anand, Priyanka; Singh, Sompal; Sarin, Namrata

    2017-09-12

    Intestinal intussusception is the most frequent cause of small bowel obstruction in children between the ages of 2 months and 5 years and often remains idiopathic in etiology, even after surgery. On microscopic examination, in intussusception normal mucosa is noted but in a few cases heterotopic tissue can be seen. Heterotopic gastric mucosa in the small intestine is extremely rare except for its occurrence in remnants of Meckel's diverticulum. In view of the rarity of this condition, we report a case of ectopic gastric mucosa in the small intestine that was not associated with remnants of vitelline duct. A 6-year-old boy of Indo-Aryan ethnicity from India presented with episodes of acute abdominal pain and distension with vomiting and non-passage of stools. On ultrasonography intussusception was suspected. A laparotomy was done and the ileal segment (tip of intussusception) was sent for histopathological examination. On histopathology, sections from the tip of intussusception showed extensive gastric metaplasia of the mucosa. A definitive diagnosis of heterotopic gastric mucosa is established by histopathological examination and it is important to differentiate heterotopia, which is a developmental anomaly, from metaplasia, which is an acquired condition. Heterotopic gastric mucosa is usually clinically silent and surgical intervention can be considered in patients with complications such as gastrointestinal hemorrhage and intestinal obstruction.

  13. Massive degeneration and atrophy of the native heart after heterotopic transplantation: a case report.

    PubMed

    Fiorelli, A I; Coelho, G H B; Lima, J L; Lourenço, D D F; Gutierres, P; Bacal, F; Bocchi, E; Dias, R R; Stolf, N A G

    2009-04-01

    Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.

  14. 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.

  15. Different ossification patterns of intermuscular bones in fish with different swimming modes

    PubMed Central

    Yao, Wenjie; Lv, Yaoping; Gong, Xiaoling; Wu, Jiaming; Bao, Baolong

    2015-01-01

    ABSTRACT Intermuscular bones are found in the myosepta in teleosts. However, there is very little information on the development and ossification of these intermuscular bones. In this study, we performed an in-depth investigation of the ossification process during development in zebrafish (Danio rerio) and Japanese eel (Anguilla japonica). In Japanese eel, a typical anguilliform swimmer, the intermuscular bones ossified predominantly from the anterior to the posterior. By contrast, in the zebrafish, a sub-carangiform or carangiform swimmer, the intermuscular bones ossified predominantly from the posterior to the anterior regions of the fish. Furthermore, tail amputation affected the ossification of the intermuscular bones. The length of the intermuscular bones in the posterior area became significantly shorter in tail-amputated zebrafish and Japanese eels, and both had less active and lower swimming speeds; this indicates that swimming might induce the ossification of the intermuscular bones. Moreover, when a greater length of tail was amputated in the zebrafish, the intermuscular bones became even shorter. Tail amputation affected the length and ossification of intermuscular bones in the anterior part of the fish, close to the head, differently between the two fish: they became significantly shorter in the zebrafish, but did not in the Japanese eel. This might be because tail amputation did not significantly affect the undulations in the anterior of the Japanese eel, especially near the head. This study shows that the ossification of intermuscular bones might be induced through mechanical force loadings that are produced by swimming. PMID:26603470

  16. 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.

  17. Evolutionary origin of endochondral ossification: the transdifferentiation hypothesis.

    PubMed

    Cervantes-Diaz, Fret; Contreras, Pedro; Marcellini, Sylvain

    2017-03-01

    The vertebrate endoskeleton results from the piecemeal assembly of bone and cartilage as well as additional types of calcified extracellular matrices produced by seemingly hybrid cell types of intermediate phenotypes between osteoblasts and chondrocytes. Hence, shedding light on the emergence and subsequent diversification of skeletal tissues represents a major challenge in vertebrate evolutionary developmental biology. A 150-year-old debate in the field was recently solved by lineage tracing experiments demonstrating that, during mouse endochondral bone development, a subset of chondrocytes evades apoptosis and transdifferentiates into osteoblasts at the chondro-osseous junction. Here, we interpret these new data from a broad phylogenetic perspective, integrating fossil, histological, cellular, and genetic evidence from a wide range of vertebrates. We propose a testable scenario according to which transdifferentiation played a fundamental role in the emergence of endochondral ossification, an osteichthyan-specific evolutionary novelty. The remarkable skeletal cell plasticity might be contingent on the similar architectures of the osteoblastic and chondrocytic gene regulatory networks, thereby providing a unifying mechanism underlying both complete transdifferentiation as well as partial cell type conversions observed in intermediate skeletal tissues such as the chondroid bone or globuli ossei.

  18. Evolution and functional significance of derived sternal ossification patterns in ornithothoracine birds

    PubMed Central

    O’connor, J. K.; Zheng, X.-T.; Sullivan, C.; Chuong, C.-M.; Wang, X.-L.; Li, A.; Wang, Y.; Zhang, X.-M.; Zhou, Z.-H.

    2017-01-01

    The midline pattern of sternal ossification characteristic of the Cretaceous enantiornithine birds is unique among the Ornithodira, the group containing birds, nonavian dinosaurs and pterosaurs. This has been suggested to indicate that Enantiornithes is not the sister group of Ornithuromorpha, the clade that includes living birds and their close relatives, which would imply rampant convergence in many nonsternal features between enantiornithines and ornithuromorphs. However, detailed comparisons reveal greater similarity between neornithine (i.e. crown group bird) and enantiornithine modes of sternal ossification than previously recognized. Furthermore, a new subadult enantiornithine specimen demonstrates that sternal ossification followed a more typically ornithodiran pattern in basal members of the clade. This new specimen, referable to the Pengornithidae, indicates that the unique ossification pattern observed in other juvenile enantiornithines is derived within Enantiornithes. A similar but clearly distinct pattern appears to have evolved in parallel in the ornithuromorph lineage. The atypical mode of sternal ossification in some derived enantiornithines should be regarded as an autapomorphic condition rather than an indication that enantiornithines are not close relatives of ornithuromorphs. Based on what is known about molecular mechanisms for morphogenesis and the possible selective advantages, the parallel shifts to midline ossification that took place in derived enantiornithines and living neognathous birds appear to have been related to the development of a large ventral keel, which is only present in ornithuromorphs and enantiornithines. Midline ossification can serve to medially reinforce the sternum at a relatively early ontogenetic stage, which would have been especially beneficial during the protracted development of the superprecocial Cretaceous enantiornithines. PMID:26079847

  19. Evolution and functional significance of derived sternal ossification patterns in ornithothoracine birds.

    PubMed

    O'Connor, J K; Zheng, X-T; Sullivan, C; Chuong, C-M; Wang, X-L; Li, A; Wang, Y; Zhang, X-M; Zhou, Z-H

    2015-08-01

    The midline pattern of sternal ossification characteristic of the Cretaceous enantiornithine birds is unique among the Ornithodira, the group containing birds, nonavian dinosaurs and pterosaurs. This has been suggested to indicate that Enantiornithes is not the sister group of Ornithuromorpha, the clade that includes living birds and their close relatives, which would imply rampant convergence in many nonsternal features between enantiornithines and ornithuromorphs. However, detailed comparisons reveal greater similarity between neornithine (i.e. crown group bird) and enantiornithine modes of sternal ossification than previously recognized. Furthermore, a new subadult enantiornithine specimen demonstrates that sternal ossification followed a more typically ornithodiran pattern in basal members of the clade. This new specimen, referable to the Pengornithidae, indicates that the unique ossification pattern observed in other juvenile enantiornithines is derived within Enantiornithes. A similar but clearly distinct pattern appears to have evolved in parallel in the ornithuromorph lineage. The atypical mode of sternal ossification in some derived enantiornithines should be regarded as an autapomorphic condition rather than an indication that enantiornithines are not close relatives of ornithuromorphs. Based on what is known about molecular mechanisms for morphogenesis and the possible selective advantages, the parallel shifts to midline ossification that took place in derived enantiornithines and living neognathous birds appear to have been related to the development of a large ventral keel, which is only present in ornithuromorphs and enantiornithines. Midline ossification can serve to medially reinforce the sternum at a relatively early ontogenetic stage, which would have been especially beneficial during the protracted development of the superprecocial Cretaceous enantiornithines. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology

  20. Heterotopically induced bone marrow. I. Cellular composition of bone marrow derived from the heterotopic ossicles induced in mice by xenogeneic epithelia of human amnion and dog's transitional epithelium.

    PubMed

    Włodarski, K; Jakóbisiak, M

    1978-01-01

    Following heterotopic osteogenesis by implantation of xenogeneic epithelia (FL and WISH cell line, transitional epithelium of dog) in mice a biogenesis of hemopoietic tissue among induced ossicles is observed. Precursors and mature forms of all types of blood cells are found in the induced bone marrow. The concentration of lymphocytes in the induced bone marrow is higher, and that of erythropoietic cells lower as compared with orthotopic femur bone marrow. The yield of myeloid cells varied from 0.14 to 3.61 x 10(6) cells per induced bone-containing nodule.

  1. BMP-2-induced Neuroforaminal Bone Growth in the Setting of a Minimally Invasive Transforaminal Lumbar Interbody Fusion.

    PubMed

    Ahn, Junyoung; Tabaraee, Ehsan; Singh, Kern

    2015-06-01

    Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has become a popular alternative to traditional methods of lumbar decompression and fusion. When compared with the open technique, the minimally invasive approach can result in decreased pain and blood loss as well as a shorter length of hospitalization. However, the narrower working channel through the tubular retractor increases the difficulty of decortication and bone grafting. Therefore, recombinant human bone morphogenetic proteins (rhBMP-2) is often utilized (although this is off-label) to create a more favorable interbody fusion environment. Recently, the use of rhBMP-2 has been associated with excessive bone growth in an MIS-TLIF. If this bone growth compresses the neighboring neural structures, patients may present with either new or recurrent radicular pain. Computed tomographic (CT) imaging can demonstrate heterotopic bone growth extending from the disk space into either the ipsilateral neuroforamen or lateral recess, which may result in the compression of the exiting or traversing root, respectively. The purpose of this article and the accompanying video is to demonstrate a technique for defining and resecting rhBMP-2-induced heterotopic bone growth following a previous MIS-TLIF.

  2. A rare and interesting case of heterotopic cervical pregnancy after intracytoplasmic sperm injection and embryo transfer

    PubMed Central

    Punhani, Ritu; Shankar, Kundavi; Varma, Thankam R.

    2016-01-01

    The wide use of assisted reproductive technologies has contributed to the increased risk of ectopic and subsequently heterotopic pregnancy (HP) rate. Cervical ectopic pregnancy is a very rare and life-threatening form of ectopic pregnancy that can also present as HP. We are describing here a case of 34-year-old woman who presented with bleeding heterotopic cervical pregnancy (HCP). The concomitant viable cervical and intrauterine pregnancies were diagnosed at 8 weeks of gestation. Selective fetal reduction was done for cervical pregnancy following which uterine artery embolization was done as a life-saving measure, and subsequently, injection methotrexate was also given. Although cervical component of HCP has the potential for high morbidity due to massive hemorrhage, the mortality rate is low due to early ultrasonographic diagnosis. A high index of suspicion is mandatory for early diagnosis. PMID:28216915

  3. Spontaneous perforation in the upper oesophagus resulting from ulcer in heterotopic gastric mucosa.

    PubMed

    Righini, C A; Faure, Cl; Karkas, A; Schmerber, S; Reyt, E

    2007-01-01

    Heterotopic gastric mucosa (HGM) can be found throughout the entire gastrointestinal tract, more frequently in the cervical oesophagus. Macroscopic HGM is named inlet patch (IP). The great majority of IPs are asymptomatic and discovered incidently during oesophageal endoscopy performed for another pathology. However, complications can occur. Among these, perforation is extremely rare. We report a case of a 27-year old man who presented with a perforation of an upper oesophageal ulcer arising from an IP. The diagnosis was made during endoscopy and confirmed with biopsy of the tissue surrounding the perforation, showing histologic modifications consistent with heterotopic gastric mucosa. Medical treatment using a proton pump inhibitor and antibiotics delivered with a gastric tube was advocated. The perforation was closed at day 7 and plasma Argon coagulation of the inlet patch was performed two months later. Annual endoscopy has been normal for three years.

  4. 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.

  5. Heterotopic gestation with subsequent live birth in a Jehovah s Witness: a case report.

    PubMed

    Kolawole, A O D; Zayyan, M S; Onwuhafua, P I

    2010-06-01

    Heterotopic gestations occurring in spontaneous conception cycles are rare. An incidence of in has been documented. However there is a rising rate mostly attributed to ovulation induction and assisted reproduction techniques where it occurs in to of all clinical pregnancies. A high index of suspicion and use of ancillary investigations will aid diagnosis. The management of this condition in a Jehovah s Witness presents an uncommon challenge as surgical intervention aims to salvage the intrauterine pregnancy whilst giving scrupulous attention to haemostasis. This is because blood transfusion is precluded in the management of haemorrhage in members of this sect. We present a case of heterotopic gestation that occurred spontaneously in a Jehovah s Witness she had emergency salpingectomy and subsequently had spontaneous vertex delivery of a live baby at term.

  6. 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.

  7. Ruptured heterotopic pregnancy: a case report and brief review of the literature.

    PubMed

    Spiff, A I; Inimgba, N M; Jamabo, R S

    2005-01-01

    Ruptured heterotopic pregnancy as a cause of acute abdomen is not commonly seen. The aim of this case report is to stress the importance of sonographic examination of the pelvic region in all symptomatic patients in the first trimester of pregnancy. The case report of a 23-year-old female with a ruptured heterotopic pregnancy is presented together with a brief review of the literature. A 23 year old female presented with signs and symptoms of an acute abdomen. She gave a history of 8 weeks amenorrhoea. Ultrasound scan (USS) showed an intra uterine pregnancy coexisting with a tubal pregnancy. All patients with symptoms of abdominal pain and history of amenorrhoea should have a sonographic examination of the pelvic region.

  8. Heterotopic new bone formation causes resorption of the inductive bone matrix

    SciTech Connect

    Nilsson, O.S.; Persson, P.E.; Ekelund, A. )

    1990-08-01

    The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM.

  9. From baby to man with a piggyback heart: long-term success of heterotopic heart transplantation.

    PubMed

    Holinski, Sebastian; Hausdorf, Gerd; Konertz, Wolfgang

    2016-01-01

    We present a case of a young man, who underwent heterotopic heart transplantation 20 years ago, when he was 6 months old. The baby suffered from severe intractable cardiomyopathy. In this desperate situation only a miniature, compromised donor heart became available. Today, the young man is fully active under minimal immunosuppression. His surgical course is reviewed and described. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  10. A Triad of Congenital Diaphragmatic Hernia, Meckel's Diverticulum, and Heterotopic Pancreas

    PubMed Central

    Mandhan, Parkash; Al Saied, Amer; Ali, Mansour J.

    2014-01-01

    Congenital diaphragmatic hernia is a common developmental anomaly encountered by paediatric surgeons. It is known to be associated with extradiaphragmatic malformations, which include cardiac, renal, genital, and chromosomal abnormalities. Herein, we report a newborn born with concurrent congenital diaphragmatic hernia, Meckel's diverticulum, and heterotopic pancreatic tissue. This is the first case report of such a triad with description of possible mechanisms of the development. PMID:24804135

  11. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage.

    PubMed

    Shen, G

    2005-02-01

    AUTHOR: Shen G Objective -This review was compiled to explore the role of type X collagen in growth, development and remodeling of articular cartilage by elucidating the linkage between the synthesis of this protein and the phenotypic changes in chondrogenesis and the onset of endochondral ossification. The current studies closely dedicated to elucidating the role of type X collagen incorporating into chondrogenesis and endochondral ossification of articular cartilage were assessed and analyzed to allow for obtaining the mainstream consensus on the bio-molecular mechanism with which type X collagen functions in articular cartilage. There are spatial and temporal correlations between synthesis of type X collagen and occurrence of endochondral ossification. The expression of type X collagen is confined within hypertrophic condrocytes and precedes the embark of endochondral bone formation. Type X collagen facilitates endochondral ossification by regulating matrix mineralization and compartmentalizing matrix components. Type X collagen is a reliable marker for new bone formation in articular cartilage. The future clinical application of this collagen in inducing or mediating endochondral ossification is perceived, e.g. the fracture healing of synovial joints and adaptive remodeling of madibular condyle.

  12. Estimation of forensic age using substages of ossification of the medial clavicle in living individuals.

    PubMed

    Ekizoglu, Oguzhan; Hocaoglu, Elif; Inci, Ercan; Can, Ismail Ozgur; Aksoy, Sema; Sayin, Ibrahim

    2015-11-01

    Forensic age estimation based on staging of ossification of the medial clavicular bone is one of the methods recommended by the Study Group on Forensic Age Diagnostics of the German Association of Forensic Medicine. In the present study, we analyzed the stages of ossification of the medial clavicular epiphyses on thin-sliced (1 mm) computed tomography (CT) images using the substages defined within stages 2 and 3. The retrospective CT analysis involved 193 subjects (129 males, 64 females) ranging in age from 13 to 28 years. Spearman's correlation analysis revealed a positive correlation between age and ossification stage in both male and female subjects. Stage 3c was first observed at 19 years of age in both sexes and may thus serve as a valuable forensic marker for determining an age of 18 years. Although further research is needed on the ossification stages of the medial clavicular epiphyses, the present findings could contribute to existing reports on observers' experiences using CT analysis of ossification combined with analysis of substages.

  13. 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.

  14. Chondrocyte-specific ablation of Osterix leads to impaired endochondral ossification

    SciTech Connect

    Oh, Jung-Hoon; Park, Seung-Yoon; Crombrugghe, Benoit de; Kim, Jung-Eun

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Conditional ablation of Osterix (Osx) in chondrocytes leads to skeletal defects. Black-Right-Pointing-Pointer Osx regulates chondrocyte differentiation and bone growth in growth plate chondrocytes. Black-Right-Pointing-Pointer Osx has an autonomous function in chondrocytes during endochondral ossification. -- Abstract: Osterix (Osx) is an essential transcription factor required for osteoblast differentiation during both intramembranous and endochondral ossification. Endochondral ossification, a process in which bone formation initiates from a cartilage intermediate, is crucial for skeletal development and growth. Osx is expressed in differentiating chondrocytes as well as osteoblasts during mouse development, but its role in chondrocytes has not been well studied. Here, the in vivo function of Osx in chondrocytes was examined in a chondrocyte-specific Osx conditional knockout model using Col2a1-Cre. Chondrocyte-specific Osx deficiency resulted in a weak and bent skeleton which was evident in newborn by radiographic analysis and skeletal preparation. To further understand the skeletal deformity of the chondrocyte-specific Osx conditional knockout, histological analysis was performed on developing long bones during embryogenesis. Hypertrophic chondrocytes were expanded, the formation of bone trabeculae and marrow cavities was remarkably delayed, and subsequent skeletal growth was reduced. The expression of several chondrocyte differentiation markers was reduced, indicating the impairment of chondrocyte differentiation and endochondral ossification in the chondrocyte-specific Osx conditional knockout. Taken together, Osx regulates chondrocyte differentiation and bone growth in growth plate chondrocytes, suggesting an autonomous function of Osx in chondrocytes during endochondral ossification.

  15. Heterotopic Procedures in Mutilating Hand Injuries: A Synopsis of Essential Reconstructive Tools.

    PubMed

    Kokkoli, Effrosyni; Spyropoulou, Georgia-Alexandra; Shih, Hsiang-Shun; Feng, Guan-Ming; Jeng, Seng-Feng

    2015-11-01

    In the complex and challenging treatment of a mutilating hand injury, any available resources need to be primarily recruited. Besides direct digital replantation, the tissue of the nonreplantable "spare parts" could often be "recycled," and also some replantable or injured structures could be "redistributed" in a more functional individualized pattern, irrespective of their initial origin. Ten patients, six male and four female, were treated for multidigital mutilating injury with various "heterotopic" procedures. Immediate digital heterotopic replantations were performed in seven patients. In one case, the bone and skin of a nonreplantable digital part were used as grafts in the reconstruction of a metacarpal bone and the overlying skin defect. A neurovascular fillet flap from a nonreplantable finger for the reconstruction of the webspace and a pollicization of an injured index were undertaken in two further cases. Another patient underwent pedicled transfer of the proximal interphalangeal joint and metacarpal bone of an impaired index to the middle finger. Sensate prehensile function was restored in 100 percent of the cases, and the ability for tripod pinch and more subtle tasks was restored in 90 percent. The minimum of two long fingers and a thumb was restored in every case, and the patients judged the appearance of their hands as "acceptable." In the reconstruction of a mutilating hand injury, besides and beyond the straightforward microsurgery, the various heterotopic procedures are essential reconstructive tools that can enhance the versatility of the hand surgeon when pursuing a better outcome. Therapeutic, IV.

  16. Nuclear magnetic resonance and proton relaxation times in experimental heterotopic heart transplantation

    SciTech Connect

    Eugene, M.; Lechat, P.; Hadjiisky, P.; Teillac, A.; Grosgogeat, Y.; Cabrol, C.

    1986-01-01

    It should be possible to detect heart transplant rejection by nuclear magnetic resonance (NMR) imaging if it induces myocardial T1 and T2 proton relaxation time alterations or both. We studied 20 Lewis rats after a heterotopic heart transplantation. In vitro measurement of T1 and T2 was performed on a Minispec PC20 (Bruker) 3 to 9 days after transplantation. Histologic analysis allowed the quantification of rejection process based on cellular infiltration and myocardiolysis. Water content, a major determinant of relaxation time, was also studied. T1 and T2 were significantly prolonged in heterotopic vs orthotopic hearts (638 +/- 41 msec vs 606 +/- 22 msec for T1, p less than 0.01 and 58.2 +/- 8.4 msec vs 47.4 +/- 1.9 msec for T2, p less than 0.001). Water content was also increased in heterotopic hearts (76.4 +/- 2.3 vs 73.8 +/- 1.0, p less than 0.01). Most importantly, we found close correlations between T1 and especially T2 vs water content, cellular infiltration, and myocardiolysis. We conclude that rejection reaction should be noninvasively detected by NMR imaging, particularly with pulse sequences emphasizing T2.

  17. 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

  18. Cross-sectional study of the neural ossification centers of vertebrae C1-S5 in the human fetus.

    PubMed

    Szpinda, Michał; Baumgart, Mariusz; Szpinda, Anna; Woźniak, Alina; Mila-Kierzenkowska, Celestyna

    2013-10-01

    An understanding of the normal evolution of the spine is of great relevance in the prenatal detection of spinal abnormalities. This study was carried out to estimate the length, width, cross-sectional area and volume of the neural ossification centers of vertebrae C1-S5 in the human fetus. Using the methods of CT (Biograph mCT), digital-image analysis (Osirix 3.9) and statistics (the one-way ANOVA test for paired data, the Kolmogorov-Smirnov test, Levene's test, Student's t test, the one-way ANOVA test for unpaired data with post hoc RIR Tukey comparisons) the size for the neural ossification centers throughout the spine in 55 spontaneously aborted human fetuses (27 males, 28 females) at ages of 17-30 weeks was studied. The neural ossification centers were visualized in the whole pre-sacral spine, in 74.5 % for S1, in 61.8 % for S2, in 52.7 % for S3, and in 12.7 % for S4. Neither male-female nor right-left significant differences in the size of neural ossification centers were found. The neural ossification centers were the longest within the cervical spine. The maximum values referred to the axis on the right, and to C5 vertebra on the left. There was a gradual decrease in length for the neural ossification centers of T1-S4 vertebrae. The neural ossification centers were the widest within the proximal thoracic spine and narrowed bi-directionally. The growth dynamics for CSA of neural ossification centers were found to parallel that of volume. The largest CSAs and volumes of neural ossification centers were found in the C3 vertebra, and decreased in the distal direction. The neural ossification centers show neither male-female nor right-left differences. The neural ossification centers are characterized by the maximum length for C2-C6 vertebrae, the maximum width for the proximal thoracic spine, and both the maximum cross-sectional area and volume for C3 vertebra. There is a sharp decrease in size of the neural ossification centers along the sacral spine. A

  19. Bilateral osteochondrosis of the primary patellar ossification centers in a young athlete: a case report.

    PubMed

    Dharamsi, Aisha S; Carl, Rebecca L

    2014-01-01

    : Osteochondroses are a group of idiopathic self-limited conditions seen in skeletally immature individuals. The term describes disturbances in endochondral ossification affecting either the primary or secondary ossification centers. Osteochondrosis of the tarsal navicular was first described by Köhler in 1908; the eponym "Köhler's disease" is commonly used to refer to this condition. In his original paper, Köhler also described one instance of an osteochondrosis of the primary patellar ossification center, a clinical entity that has since rarely been reported. We present a case of isolated bilateral "Köhler's disease of the patellae" in an approximately 7-year-old male athlete demonstrated clinically and radiographically by both plain radiographs and magnetic resonance imaging.

  20. Fetal maturity and morbidity as related to placental weight and secondary ossification

    PubMed Central

    Pryse-Davies, J.

    1975-01-01

    The problem of objectivity in histopathology is illustrated by an attempt to determine the normal range and significance of two observations, placental weight and secondary ossification, made in perinatal pathology. Neither offered a satisfactory estimation of fetal maturity. The placental weight provided little evidence of any primary placental dysfunction: the placenta was very small in association with only 50% of the very small infants and a very small placental fetal weight ratio was an infrequent finding of doubtful significance. A method of classifying relatively retarded and advanced secondary ossification was devised. Significant retardation was found in association with males, growth retardation, some malformations, and multiple births: significantly advanced ossification was found in anencephaly. PMID:1197178

  1. Developmental differences in the ossification process of the human corpus and ramus mandibulae.

    PubMed

    Merida-Velasco, J A; Sanchez-Montesinos, I; Espin-Ferra, J; Garcia-Garcia, J D; Roldan-Schilling, V

    1993-02-01

    A correlation was sought between the organization of the dental crest and the ossification of the corpus mandibulae in 14 human embryos and 13 human fetuses. The different types of ossification between the corpus and the ramus mandibulae suggest that the cartilago mandibularis (meckeliensis) guides the formation of the mandibula, while the dental crest acts as a coorganizer. In the area of the foramen mentale, the lamina dentalis begins to invaginate (to give rise to the dental crest), and at this level intramembranous ossification of the corpus mandibulae commences. These findings, together with the presence of the cartilago mandibularis before the appearance of the dental crest, and the fact that the former is seen along the entire length of the mandibula (from the symphysis mandibulae to the capsula otica), support the hypothesis that the dental crest, rather than the cartilago mandibularis, acts as the coorganizer in the corpus mandibulae.

  2. Inner ear ossification and mineralization kinetics in human embryonic development - microtomographic and histomorphological study.

    PubMed

    Richard, Céline; Courbon, Guillaume; Laroche, Norbert; Prades, Jean Michel; Vico, Laurence; Malaval, Luc

    2017-07-06

    Little is known about middle and inner ear development during the second and third parts of human fetal life. Using ultra-high resolution Microcomputed Tomography coupled with bone histology, we performed the first quantitative middle and inner ear ossification/mineralization evaluation of fetuses between 17 and 39 weeks of gestational age. We show distinct ossification paces between ossicles, with a belated development of the stapes. A complete cochlear bony covering is observed within the time-frame of the onset of hearing, whereas distinct time courses of ossification for semicircular canal envelopes are observed in relation to the start of vestibular functions. The study evidences a spatio-temporal relationship between middle and inner ear structure development and the onset of hearing and balance, critical senses for the fetal adaptation to birth.

  3. Bilateral ossification of the auricles: an unusual entity and review of the literature

    PubMed Central

    Mastronikolis, Nicholas S; Zampakis, Peter; Kalogeropoulou, Christina; Stathas, Theodoros; Siabi, Vassiliki; Geropoulou, Eleni; Goumas, Panos D

    2009-01-01

    Background True ossification of the auricle with cartilage replacement by bone, is a very rare clinical entity and can result in an entirely rigid auricle. Case presentation We present a rare case of bilateral ossification of the auricles in a 75-years old man with profound progressive rigidity of both auricles. His main complaint was a mild discomfort during resting making sleeping unpleasant without any other serious symptoms. His medical history was significant for predisposing factors for this condition such as, Addison's disease and diabetes mellitus. Excisional biopsy was performed confirming the ossified nature of the auricles. Further treatment deemed unnecessary in our case due to his mild clinical picture. Conclusion True auricular ossification is a quite rare clinical entity with unclear pathogenesis and one should have in mind that there is always the possibility of a serious co-existed disease like endocrinopathy. PMID:19796391

  4. 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.

  5. Does the epiphyseal cartilage of the long bones have one or two ossification fronts?

    PubMed

    Delgado-Martos, María Jesús; Touza Fernández, Alberto; Canillas, Fernando; Quintana-Villamandos, Begoña; Santos del Riego, Sergio; Delgado-Martos, Emilio; Martos-Rodriguez, Antonia; Delgado-Baeza, Emilio

    2013-10-01

    Epiphyseal cartilage is hyaline cartilage tissue with a gelatinous texture, and it is responsible for the longitudinal growth of the long bones in birds and mammals. It is located between the epiphysis and the diaphysis. Epiphyseal cartilage also is called a growth plate or physis. It is protected by three bone components: the epiphysis, the bone bar of the perichondrial ring and the metaphysis. The epiphysis, which lies over the epiphyseal cartilage in the form a cupola, contains a juxtaposed bone plate that is near the epiphyseal cartilage and is in direct contact with the epiphyseal side of the epiphyseal cartilage. The germinal zone corresponds to a group of cells called chondrocytes. These chondrocytes belong to a group of chondral cells, which are distributed in rows and columns; this architecture is commonly known as a growth plate. The growth plate is responsible for endochondral bone growth. The aim of this study was to elucidate the causal relationship between the juxtaposed bone plate and epiphyseal cartilage in mammals. Our hypothesis is that cells from the germinal zone of the epiphyseal side of the epiphyseal cartilage are involved in forming a second ossification front that is responsible for the origin of the juxtaposed bone plate. We report the following: (a) The juxtaposed bone plate has a morphology and function that differs from that of the epiphyseal trabeculae; (b) on the epiphyseal edge of the epiphyseal cartilage, a new ossification front starts on the chondrocytes of the germinal area, which forms the juxtaposed bone plate. This ossification front is formed by chondrocytes from the germinal zone through a process of mineralisation and ossification, and (c) the process of mineralisation and ossification has a certain morphological analogy to the process of ossification in the metaphyseal cartilage of amphibians and differs from the endochondral ossification process in the metaphyseal side of the growth plate. The close relationship between

  6. Ossification in the caudal attachments of the ligamentum flavum: an anatomic and computed tomographic study

    SciTech Connect

    Williams, D.M.; Gabrielson, T.O.; Latack, J.T.

    1982-12-01

    A review of anatomic specimens and routine computed tomographic (CT) scans of the chest and abdomen demonstrated that ossification in the caudal attachments of the ligamentum flavum is a common anatomic finding, but a much less common CT finding. Its characteristic location should help prevent confusion with other entities. The present study was prompted by a case of thoracic spine trauma, reported here, in which areas of bone density in the spinal canal simulated fracture fragments. The true nature of these bony projections, namely ossification in the ligamentum flavum, was established by computer reconstruction of axial CT images.

  7. Ossification in an extra-intradural spinal meningioma-pathologic and surgical vistas.

    PubMed

    Chotai, Silky P; Mrak, Robert E; Mutgi, Sunil A; Medhkour, Azedine

    2013-12-01

    Intradural and intratumorous ossification in spinal meningiomas are rare compared to their cranial counterparts. Extradural extension of the spinal meningioma is not uncommon. To the best of our knowledge, the ossification in an extra-intradural spinal meningioma is not yet reported in the literature. The authors report a rare case of an extra-intradural spinal meningioma with ossification and calcification. The review of literature including the surgical challenges and the histologic variations as well as histogenesis of the ossified spinal meningioma is discussed. Case report and review of the literature. A 61-year-old woman presented with complaints of numbness and weakness for 3 years, and gait disturbances for 6 months. Magnetic resonance imaging revealed a mass compressing the spinal cord at the T4 level. Complete resection of the tumor was achieved with coagulation and partial resection of the dura. Histopathological examination demonstrated a psammomatous spinal meningioma with intratumorous and intradural mature lamellar bone formation, complete with marrow and hematopoietic cells. The patient is asymptomatic at 3-year postoperative follow-up. Despite adherence of the ossified mass to the dura, arachnoid, and spinal cord, complete atraumatic resection of the mass was possible with favorable surgical outcome. In addition to calcification as a likely forerunner of ossification in the psammomatous subtype of meningioma, metaplastic differentiation of neoplastic cells to osseous and hematopoietic component might play a crucial role. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Forensic age estimation in living subjects based on ultrasound examination of the ossification of the olecranon.

    PubMed

    Schulz, Ronald; Schiborr, Manfred; Pfeiffer, Heidi; Schmidt, Sven; Schmeling, Andreas

    2014-02-01

    Radiation-free imaging procedures for the purposes of forensic age diagnosis are highly desirable, especially for children. With this in mind, the stage of ossification of the olecranon was prospectively determined in 309 male and 307 female healthy volunteers aged between 10 and 25 years, based on ultrasound. A four-stage classification system was used for this purpose. This stage classification system takes into account whether an isolated secondary ossification centre, an epiphyseal cartilage or an epiphysis which is completely fused with the diaphysis can be detected. The earliest observation of stage 2 was at 10.0 years in males and 10.1 years in females. Both findings are determined by the lower age limit of the sample and are thus not representative of the minimum age for ossification stage 2. Stage 3 was first noticed at age 13.5 years in males and 10.6 years in females. Stage 4 was first reached at age 13.7 years in males and 12.3 years in females. Hence, in our sample, ossification stage 3 can be seen as evidence that females have reached the age of 10 years and males the age of 13 years. In our sample, stage 4 provides evidence that a female individual has reached the age of 12 years. It was concluded that the results of our study should be validated using other samples. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  9. Human penile ossification: a case report and review of the literature.

    PubMed

    Frank, R G; Gerard, P S; Wise, G J

    1989-01-01

    Human penile ossification is a rare event. Only a limited number of cases have appeared in the literature. Several reported cases have been related to local trauma and plastic induration of the penis. We report an additional case with a comprehensive review of case reports in the literature.

  10. Diffuse pulmonary ossification detected by bone scanning with Tc-99m hydroxymethylene diphosphate

    SciTech Connect

    Saks, D.A.; McClees, E.C.; Fajman, W.A.; Hollinger, W.M.; Gilman, M.J.

    1984-10-01

    Diffuse pulmonary ossification (DPO) is a rare pathologic finding of heterotropic bone formation within the lungs. It has been associated with mitral stenosis, chronic left ventricular failure, interstitial fibrosis, metastatic breast cancer, pulmonary amyloidosis, histoplasmosis, and chronic busulfan therapy. This patient represents a case associated with Placidyl use.

  11. Timing of Ossification in Duck, Quail, and Zebra Finch: Intraspecific Variation, Heterochronies, and Life History Evolution

    PubMed Central

    Mitgutsch, Christian; Wimmer, Corinne; Sánchez-Villagra, Marcelo R.; Hahnloser, Richard; Schneider, Richard A.

    2011-01-01

    Skeletogenic heterochronies have gained much attention in comparative developmental biology. The temporal appearance of mineralized individual bones in a species – the species ossification sequence – is an excellent marker in this kind of study. Several publications describe interspecific variation, but only very few detail intraspecific variation. In this study, we describe and analyze the temporal order of ossification of skeletal elements in the zebra finch, Taeniopygia guttata, the Japanese quail, Coturnix coturnix japonica, and the White Pekin duck, a domestic race of the mallard Anas platyrhynchos, and explore patterns of intraspecific variation in these events. The overall sequences were found to be conserved. In the duck, variability is present in the relative timing of ossification in the occipital, the basisphenoid and the otic regions of the skull and the phalanges in the postcranium. This variation appears generally in close temporal proximity. Comparison with previously published data shows differences in ossification sequence in the skull, the feet, and the pelvis in the duck, and especially the pelvis in the quail. This clearly documents variability among different breeds. PMID:21728797

  12. Heterotopic cardiac transplantation decreases the capacity for rat myocardial protein synthesis

    SciTech Connect

    Klein, I.; Samarel, A.M.; Welikson, R.; Hong, C. )

    1991-04-01

    Heterotopic cardiac isografts are vascularly perfused hearts that maintain structural and functional integrity for prolonged periods of time. When placed in an infrarenal location, the heart is hemodynamically unloaded and undergoes negative growth, leading to cardiac atrophy. At 7 and 14 days after transplantation, the transplanted heart was decreased in size compared with the in situ heart (p less than 0.001). To assess the possible mechanism(s) to account for this reduction in size we studied in vivo rates of total left ventricular (LV) protein synthesis, total LV RNA content, and 18S ribosomal RNA content by nucleic acid hybridization. The LV protein synthetic rate was 4.7 and 5.3 mg/day in the in situ heart and was significantly decreased to 2.9 and 2.7 mg/day in the transplanted hearts at 7 and 14 days, respectively. LV RNA content of the transplant declined to 53% and 48% of the in situ value at 7 and 14 days, respectively. Hybridization studies revealed that LV 18S ribosomal subunit content was reduced proportionately to total RNA in the heterotopic hearts. As a result of these changes, there was no significant difference in the efficiency of total LV protein synthesis between the in situ and transplanted hearts. The present studies demonstrate that the hemodynamic unloading and cardiac atrophy that is characteristic of heterotopic cardiac transplantation is accompanied by a decrease in LV total RNA content and 18S RNA, resulting in a decreased capacity for myocardial protein synthesis.

  13. Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

    PubMed Central

    Fu, Xuebin; Segiser, Adrian; Carrel, Thierry P.; Tevaearai Stahel, Hendrik T.; Most, Henriette

    2016-01-01

    Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients. PMID:27807535

  14. Endochondral ossification for enhancing bone regeneration: converging native extracellular matrix biomaterials and developmental engineering in vivo.

    PubMed

    Dennis, S Connor; Berkland, Cory J; Bonewald, Lynda F; Detamore, Michael S

    2015-06-01

    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 and ECM-based designs that

  15. 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

  16. Gastric fundal heterotopic pancreas mimicking a gastrointestinal stromal tumour (GIST): a case report and a brief review.

    PubMed

    Subasinghe, Duminda; Sivaganesh, Sivasuriya; Perera, Niranthi; Samarasekera, Dharmabandhu N

    2016-03-22

    Heterotopic pancreas is a rare congenital condition characterised by pancreatic tissue lacking vascular or anatomic communication with the normal pancreas. Most cases of ectopic pancreas are asymptomatic. The preoperative diagnosis of this condition is difficult. A 50-year-old woman presented with dyspeptic symptoms of 4 years duration. Contrast enhanced CT (computed tomography) scan of abdomen suggested a gastrointestinal stromal tumour in the fundus of the stomach. The patient underwent laparoscopy assisted resection and subsequent histology revealed ectopic pancreatic tissue. Although heterotopic pancreas is a rare lesion diagnosed on histology, it should be considered in the differential diagnosis of gastric mass lesions and in patients presenting with vague upper gastrointestinal symptoms.

  17. [Successful treatment of a cervical heterotopic pregnancy following an in vitro fertilization procedure].

    PubMed

    Elena, Hernán E; Elena, Alfredo F; Miola, Anselmo; Glujovsky, Demian; Sueldo, Carlos E

    2016-01-01

    A 37-year-old nulligravida infertile female had a cervical heterotopic pregnancy following an in vitro fertilization procedure. Early intervention on the 6th week of gestation with a manual vacuum aspirator reached to remove the cervical pregnancy. Ligation of the descending cervical branches of the uterine arteries and a cervical cerclage, were placed before the aspiration, for prevention of possible hemorrhage. Successful removal of the cervical pregnancy was achieved with only mild bleeding. An intrauterine pregnancy progressed to viability without complications, resulting in a vaginal delivery of a preterm live-birth at 35.4 weeks, of a male that weighted 2740 g.

  18. Magnetic resonance imaging-based evaluation of ossification of the medial clavicular epiphysis in forensic age assessment.

    PubMed

    Schmidt, S; Ottow, C; Pfeiffer, H; Heindel, W; Vieth, V; Schmeling, A; Schulz, R

    2017-09-09

    Evaluation of the degree of ossification of the medial clavicular epiphysis plays a crucial role in determining with an adequate degree of probability whether legally relevant age boundaries after the age of 17 have been crossed. In view of the need to avoid unnecessary radiation exposure, establishing non-X-ray methods for investigating the clavicle has long been a key objective in forensic age assessment research. Based on magnetic resonance imaging examinations in a large sample of healthy subjects, the current study for the first time presents statistical measures which allow inferences to be drawn for forensic age assessment in both sexes. We undertook a prospective study of a reference sample of 334 female and 335 male German volunteers aged from 12 to 24 using a 3-T MRI scanner. A 3D FFE (fast field echo) T1-weighted sequence with fat saturation was acquired. To stage ossification of the medial clavicular epiphysis, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IIIc offers a means in both sexes of demonstrating that the age of 18 has been attained prior to complete ossification of the epiphyseal plate. In both sexes, if a subject has reached ossification stage IV, it can be stated that he or she has attained the age of 21. Magnetic resonance imaging is a valid diagnostic procedure for determining the ossification stage of the medial clavicular epiphysis.

  19. Ossification of the mouse metatarsal: differentiation and proliferation in the presence/absence of a defined growth plate.

    PubMed

    Reno, Philip L; McBurney, Denise L; Lovejoy, C Owen; Horton, Walter E

    2006-01-01

    There is significant diversity in growth plate behavior among sites within an individual skeleton and between skeletons of different species. This variation within wild-type animals is an underutilized resource for studying skeletal development. One bone that potentially exhibits the most diverse behavior is the metatarsal. While one end forms a growth plate with an epiphyseal secondary center of ossification as in other long bones, the opposite end undergoes direct ossification in a manner more similar to short bones. Although descriptions of human metatarsal/metacarpal ossification are available, a detailed comparative analysis has yet to be conducted in an animal model amenable to biomolecular analysis. Here we report an analysis of proximal and distal ossification in an age series of mouse metatarsals. Safranin O staining was used for qualitative and quantitative histology, and chondrocyte differentiation and proliferation were analyzed using immunohistochemistry for type X collagen and proliferative cell nuclear antigen expression. We establish that, as in the human, both growth plate formation and direct ossification occur in the mouse metatarsal, with chondrocyte populations showing distinct differentiation patterns at opposite ends of the bone. In addition, growth plate formation is characterized by a peak of proliferation in reserve zone chondrocytes that distinguishes it from both established growth plates and direct ossification. Our analysis demonstrates that the mouse metatarsal is a productive model for investigating natural variation in ossification that can further understanding of vertebrate skeletal development and evolution.

  20. Failure of ossification of the occipital bone in mandibuloacral dysplasia type B.

    PubMed

    Haye, Damien; Dridi, Hend; Levy, Jonathan; Lambert, Véronique; Lambert, Maurice; Agha, Mohamed; Adjimi, Frédéric; Kohlhase, Jürgen; Lipsker, Dan; Verloes, Alain

    2016-10-01

    Mandibuloacral dysplasia with type B lipodystrophy is a rare autosomal recessive disease characterized by atrophic skin, lipodystrophy, and skeletal features. It is caused by mutations in ZMPSTE24, a gene encoding a zinc metalloproteinase involved in the post-translational modification of lamin. Nine distinct pathogenic variants have been identified in 11 patients from nine unrelated families with this disorder. We report a 12-year-old boy with mandibuloacral dysplasia with type B lipodystrophy and a novel homozygous c.1196A>G; p.(Tyr399Cys) mutation in ZMPSTE24. The patient had typical dermatological and skeletal features of mandibuloacral dysplasia with type B lipodystrophy, sparse hair, short stature, mild microcephaly, facial dysmorphism, and a striking failure of ossification of the interparietal region of the occipital bone, up to the position where transverse occipital suture can be observed. Newly recognized signs for mandibuloacral dysplasia with type B lipodystrophy were gaze palsy and ptosis. Delayed closure of cranial sutures and Wormian bones have been described in three patients, but an ossification failure strictly limited to the occipital bone, as seen in the present patient, appears to be unique for mandibuloacral dysplasia with type B lipodystrophy. This observation illustrates that ZMPSTE24 could play a specific role in membranous ossification in the interparietal part of the squama (Inca bone) but not in the intracartilaginous ossification of the supraoccipital. This failure of ossification in the squama appears to be a useful feature for the radiological diagnosis of mandibuloacral dysplasia with type B lipodystrophy. © 2016 Wiley Periodicals, Inc.

  1. Triticeous Cartilage CT Imaging Characteristics, Prevalence, Extent, and Distribution of Ossification.

    PubMed

    Alqahtani, Eman; Marrero, Daniel E; Champion, Walter L; Alawaji, Ahmed; Kousoubris, Philip D; Small, Juan E

    2016-01-01

    The triticeous cartilage is a small ovoid cartilaginous structure variably present as a component of the laryngeal skeleton. This structure has received scant attention in the literature and has yet to be described adequately on cross-sectional imaging. Retrospective study in a tertiary medical center. We investigated triticeous cartilage prevalence in a large population utilizing computed tomography images. The cases of all patients with computed tomography angiography images of the neck from October 1, 2013, to September 31, 2014, were examined. A total of 663 patients were included in this study (age: range, 18-97 years; mean ± SD, 65 ± 15 years), 58.4% men and 41.6% women. The presence of a triticeal cartilage and its site, number, and degree of ossification were recorded. A total of 53.1% of patients had at least 1 triticeous cartilage (352 of 663). Prevalence was 57.4% (222 of 387) among men and 47.1% (130 of 276) among women. The presence of bilateral triticeous cartilages was more common than unilateral (63.1%, 222 of 352). A minority of patients (4.5%, 16 of 352) had a cartilaginous triticeous with no appreciable ossification, and more than half (54.0%, 190 of 352) had mild triticeal ossification. Moderate ossification was found in 34.9% of patients (123 of 352) and marked ossification in 6.5% (23 of 352). The presence of a triticeous cartilage is common and of variable appearance. As the clinical and surgical significance of this anatomic structure may be misinterpreted, it is important for imaging interpreters to be familiar with this seldom-recognized anatomic structure and recognize its variable appearance on cross-sectional imaging to avoid a misdiagnosis. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  2. 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

  3. Celastrol inhibits prostaglandin E2-induced proliferation and osteogenic differentiation of fibroblasts isolated from ankylosing spondylitis hip tissues in vitro

    PubMed Central

    Zou, Yu-Cong; Yang, Xian-Wen; Yuan, Shi-Guo; Zhang, Pei; Li, Yi-Kai

    2016-01-01

    Background Heterotopic ossification on the enthesis, which develops after subsequent inflammation, is one of the most distinctive features in ankylosing spondylitis (AS). Prostaglandin E2 (PGE-2) serves as a key mediator of inflammation and bone remodeling in AS. Celastrol, a well-known Chinese medicinal herb isolated from Tripterygium wilfordii, is widely used in treating inflammatory diseases, including AS. It has been proven that it can inhibit lipopolysac-charide-induced expression of various inflammation mediators, such as PGE-2. However, the mechanism by which celastrol inhibits inflammation-induced bone forming in AS is unclear. Objective To investigate whether celastrol could inhibit isolated AS fibroblast osteogenesis induced by PGE-2. Methods Hip synovial tissues were obtained from six AS patients undergoing total hip replacement in our hospital. Fibroblasts were isolated, primarily cultured, and then treated with PGE-2 for osteogenic induction. Different doses of celastrol and indometacin were added to observe their effects on osteogenic differentiation. Cell proliferation, osteogenic markers, alizarin red staining as well as the activity of alkaline phosphatase were examined in our study. Results Celastrol significantly inhibits cell proliferation of isolated AS fibroblasts and in vitro osteogenic differentiation compared with control groups in a time- and dose-dependent manner. Conclusion Our results demonstrated that celastrol could inhibit isolated AS fibroblast proliferation and in vitro osteogenic differentiation. The interaction of PI3K/AKT signaling and Wnt protein may be involved in the process. Further studies should be performed in vivo and animal models to identify the potential effect of celastrol on the bone metabolism of AS patients. PMID:27022241

  4. Transplantation of Pulmonary Valve Using a Mouse Model of Heterotopic Heart Transplantation

    PubMed Central

    Lee, Yong-Ung; Yi, Tai; James, Iyore; Tara, Shuhei; Stuber, Alexander J.; Shah, Kejal V.; Lee, Avione Y.; Sugiura, Tadahisa; Hibino, Narutoshi; Shinoka, Toshiharu; Breuer, Christopher K.

    2014-01-01

    Tissue engineered heart valves, especially decellularized valves, are starting to gain momentum in clinical use of reconstructive surgery with mixed results. However, the cellular and molecular mechanisms of the neotissue development, valve thickening, and stenosis development are not researched extensively. To answer the above questions, we developed a murine heterotopic heart valve transplantation model. A heart valve was harvested from a valve donor mouse and transplanted to a heart donor mouse. The heart with a new valve was transplanted heterotopically to a recipient mouse. The transplanted heart showed its own heartbeat, independent of the recipient’s heartbeat. The blood flow was quantified using a high frequency ultrasound system with a pulsed wave Doppler. The flow through the implanted pulmonary valve showed forward flow with minimal regurgitation and the peak flow was close to 100 mm/sec. This murine model of heart valve transplantation is highly versatile, so it can be modified and adapted to provide different hemodynamic environments and/or can be used with various transgenic mice to study neotissue development in a tissue engineered heart valve. PMID:25079013

  5. Unilateral twin tubal pregnancy and subsequent heterotopic pregnancy in a patient following in vitro fertilization.

    PubMed

    Kasum, Miro

    2009-09-01

    Unilateral twin tubal gestations are extremely rare with a reported incidence of 1 per 200 ectopic pregnancies. In recent years, the incidence of heterotopic pregnancy associated with in vitro fertilization and embryo transfer (IVF-ET) has risen to 1%-3% of achieved pregnancies. We report a very rare case of a 32-year-old woman with 6-year primary infertility with unilateral twin tubal pregnancy and subsequent heterotopic pregnancy following two IVF treatments. Her gynecologic history was notable for previous distal occlusion of the left fallopian tube treated by laparoscopic reconstructive surgery. After ovulation induction and IVF with ET of two embryos, transvaginal sonography at 6 weeks revealed two separate gestational sacs in the left adnexal mass. Emergency laparoscopy showed unruptured ampullar pregnancy and salpingectomy was carried out. On second IVF two years later, after ovulation induction and ET of three embryos, endovaginal sonography at 6 weeks revealed only one intrauterine sac. One week later, the patient complained of intermittent episodes of lower abdominal pain in the right quadrant. Ultrasound confirmed intrauterine pregnancy and revealed right tubal gestational sac. Laparoscopy showed unruptured right ampullar pregnancy and salpingectomy was performed. Histology of salpingectomy specimens showed signs of chronic infection in both tubes. The intrauterine pregnancy progressed to term when a healthy infant was delivered vaginally. Gynecologists should always consider the possibility of ectopic pregnancy in pregnancies following IVF-ET, particularly in cases with tubal disease and abdominal pain.

  6. Diffuse Pulmonary Ossification in Fibrosing Interstitial Lung Diseases: Prevalence and Associations.

    PubMed

    Egashira, Ryoko; Jacob, Joseph; Kokosi, Maria A; Brun, Anne-Laure; Rice, Alexandra; Nicholson, Andrew G; Wells, Athol U; Hansell, David M

    2017-07-01

    Purpose To investigate the prevalence of diffuse pulmonary ossification (DPO) in patients with fibrosing interstitial lung disease (ILD) and determine whether there are differences among the types of ILDs. Materials and Methods Institutional review board approval was given and patient consent was not required for this study. The study population comprised 892 consecutive patients with fibrosing ILD, including 456 patients with idiopathic pulmonary fibrosis (IPF) (men, 366; women, 90; median age, 72 years [range, 38-93 years]), 244 with nonspecific interstitial pneumonia (men, 79; women, 165; median age, 60.5 years [range, 23-86 years]), and 192 with chronic hypersensitivity pneumonitis (men, 76; women, 116; median age, 66 years [range, 35-88 years]). Pulmonary ossifications were recorded when nodules (<4 mm diameter) were identified on bone window images (width, 2500 HU; level, 500 HU). DPO was defined as 10 or more bilateral nodular ossifications (definition 1) or as one or more lobes with five or more bilateral nodular ossifications (definition 2). Relationships among pulmonary ossification and parenchymal patterns, clinical parameters, and multidisciplinary team diagnoses were examined. The prevalence of DPO was compared with the χ(2) statistic or Fisher exact test, and multivariate analysis was performed with logistic regression. Results In the whole population, the prevalence of DPO was 166 (18.6%) and 106 (11.9%) of 892 patients according to definitions 1 and 2, respectively. The prevalence of DPO (definition 1) was significantly higher in patients with IPF (28.5%) than in those without IPF (8.3%, P < .001). Nine of 192 (4.7%) had chronic hypersensitivity pneumonitis (P < .001), and 27 of 244 (11.1%) had nonspecific interstitial pneumonia (P < .001). At multivariate analysis, DPO according to definition 1 was an independent predictor of IPF diagnosis (P < .001) and male sex (P = .003). Coarseness of fibrosing ILD (P = .011) and IPF diagnosis (P = .016) were

  7. 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.

  8. Neuronal migration disorders: Heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex

    PubMed Central

    Chevassus-Au-Louis, N.; Congar, P.; Represa, A.; Ben-Ari, Y.; Gaïarsa, J.-L.

    1998-01-01

    Neuronal migration disorders have been involved in various pathologies, including epilepsy, but the properties of the neural networks underlying disorders have not been determined. In the present study, patch clamp recordings were made from intrahippocampal heterotopic as well as from neocortical and hippocampal neurons from brain slices of rats with prenatally methylazoxymethanol-induced cortical malformation. We report that heterotopic neurons have morphometrical parameters and cellular properties of neocortical supragranular neurons and are integrated in both neocortical and hippocampal networks. Thus, stimulation of the white matter induces both antidromic and orthodromic response in heterotopic and neocortical neurons. Stimulation of hippocampal afferents evokes a monosynaptic response in the majority of heterotopic neurons and a polysynaptic all-or-none epileptiform burst in the presence of bicuculline to block γ-aminobutyric acid type A inhibition. Furthermore, hippocampal paroxysmal activity generated by bath application of bicuculline can spread directly to the neocortex via the heterotopia in methylazoxymethanol-treated but not in naive rats. We conclude that heterotopias form a functional bridge between the limbic system and the neocortex, providing a substrate for pathological conditions. PMID:9707635

  9. Ossification of the posterior ligament is mediated by osterix via inhibition of the β-catenin signaling pathway.

    PubMed

    Shi, Lei; Cai, Guodong; Shi, Jiangang; Guo, Yongfei; Chen, Dechun; Chen, Deyu; Yang, Haisong

    2016-11-15

    Ossification of the posterior longitudinal ligament (OPLL) involves ectopic calcification of the spinal ligament preferentially at the cervical spine. OPLL is associated with different diseases and occurs by endochondral ossification, which is associated with the activity of different transcription factors. However, the pathogenesis of OPLL remains unclear. Here, we investigated the role of osterix (Osx), a transcription factor that functions downstream of Runx2 and is an important regulator of osteogenesis, in the process of OPLL in a dexamethasone (Dex)-induced model of spinal ligament ossification. Our results showed that Osx is upregulated in patients with OPLL and during the ossification of ligament cells in parallel with the upregulation of osteogenic markers including osteocalcin (OCN), alkaline phosphatase (ALP) and collagen-1 (Col-1). Dex-induced ossification of ligament cells was associated with the downregulation and inactivation of β-catenin, and these effects were offset by Osx knockdown. Activation of β-catenin signaling abolished the effect of Dex on ossification and the upregulation of osteogenic markers. Taken together, our results suggest that OPLL is mediated by Osx via a mechanism involving the Wnt/β-catenin signaling pathway, providing a basis for further research to identify potential targets for the treatment of OPLL.

  10. Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Regulates Chondrocyte Differentiation and Secondary Ossification in Mice

    PubMed Central

    Cheng, Shaohong; Aghajanian, Patrick; Pourteymoor, Sheila; Alarcon, Catrina; Mohan, Subburaman

    2016-01-01

    Endochondral ossification plays an important role in the formation of the primary ossification centers (POCs) and secondary ossification centers (SOCs) of mammalian long bones. However, the molecular mechanisms that regulate POC and SOC formation are different. We recently demonstrated that Prolyl Hydroxylase Domain-containing Protein 2 (Phd2) is a key mediator of vitamin C effects on bone. We investigated the role of Phd2 on endochondral ossification of the epiphyses by conditionally deleting the Phd2 gene in osteoblasts and chondrocytes. We found that the deletion of Phd2 in osteoblasts did not cause changes in bone parameters in the proximal tibial epiphyses in 5 week old mice. In contrast, deletion of Phd2 in chondrocytes resulted in increased bone mass and bone formation rate (normalized to tissue volume) in long bone epiphyses, indicating that Phd2 expressed in chondrocytes, but not osteoblasts, negatively regulates secondary ossification of epiphyses. Phd2 deletion in chondrocytes elevated mRNA expression of hypoxia-inducible factor (HIF) signaling molecules including Hif-1α, Hif-2α, Vegfa, Vegfb, and Epo, as well as markers for chondrocyte hypertrophy and mineralization such as Col10, osterix, alkaline phosphatase, and bone sialoprotein. These data suggest that Phd2 expressed in chondrocytes inhibits endochondral ossification at the epiphysis by suppressing HIF signaling pathways. PMID:27775044

  11. Stimulation of experimental endochondral ossification by low-energy pulsing electromagnetic fields

    SciTech Connect

    Aaron, R.K.; Ciombor, D.M.; Jolly, G.

    1989-04-01

    Pulsed electromagnetic fields (PEMFs) of certain configuration have been shown to be effective clinically in promoting the healing of fracture nonunions and are believed to enhance calcification of extracellular matrix. In vitro studies have suggested that PEMFs may also have the effect of modifying the extracellular matrix by promoting the synthesis of matrix molecules. This study examines the effect of one PEMF upon the extracellular matrix and calcification of endochondral ossification in vivo. The synthesis of cartilage molecules is enhanced by PEMF, and subsequent endochondral calcification is stimulated. Histomorphometric studies indicate that the maturation of bone trabeculae is also promoted by PEMF stimulation. These results indicate that a specific PEMF can change the composition of cartilage extracellular matrix in vivo and raises the possibility that the effects on other processes of endochondral ossification (e.g., fracture healing and growth plates) may occur through a similar mechanism.

  12. Vascularization of primary and secondary ossification centres in the human growth plate

    PubMed Central

    2014-01-01

    Background The switch from cartilage template to bone during endochondral ossification of the growth plate requires a dynamic and close interaction between cartilage and the developing vasculature. Vascular invasion of the primarily avascular hypertrophic chondrocyte zone brings chondroclasts, osteoblast- and endothelial precursor cells into future centres of ossification. Vascularization of human growth plates of polydactylic digits was studied by immunohistochemistry, confocal-laser-scanning-microscopy and RT-qPCR using markers specific for endothelial cells CD34 and CD31, smooth muscle cells α-SMA, endothelial progenitor cells CD133, CXCR4, VEGFR-2 and mesenchymal progenitor cells CD90 and CD105. In addition, morphometric analysis was performed to quantify RUNX2+ and DLX5+ hypertrophic chondrocytes, RANK+ chondro- and osteoclasts, and CD133+ progenitors in different zones of the growth plate. Results New vessels in ossification centres were formed by sprouting of CD34+ endothelial cells that did not co-express the mature endothelial cell marker CD31. These immature vessels in the growth plate showed no abluminal coverage with α-SMA+ smooth muscle cells, but in their close proximity single CD133+ precursor cells were found that did not express VEGFR-2, a marker for endothelial lineage commitment. In periosteum and in the perichondrial groove of Ranvier that harboured CD90+/CD105+ chondro-progenitors, in contrast, mature vessels were found stabilized by α-SMA+ smooth muscle cells. Conclusion Vascularization of ossification centres of the growth plate was mediated by sprouting of capillaries coming from the bone collar or by intussusception rather than by de-novo vessel formation involving endothelial progenitor cells. Vascular invasion of the joint anlage was temporally delayed compared to the surrounding joint tissue. PMID:25164565

  13. Microvascular features and ossification process in the femoral head of growing rats

    PubMed Central

    MORINI, SERGIO; PANNARALE, LUIGI; FRANCHITTO, ANTONIO; DONATI, SAARA; GAUDIO, EUGENIO

    1999-01-01

    In the epiphysis of long bones, different patterns of development of ossification processes have been described in different species. The development of the vascularisation of the femoral head has not yet been fully clarified, although its role in the ossification process is obvious. Our aim was to investigate ossification and vascular proliferation and their relationship, in growing rat femoral heads. Male Wistar rats aged ∼ 1, 5 and 8 wk and 4, 8 and 12 mo were used. Light microscopy frontal sections and vascular corrosion casts observed by scanning electron microscopy were employed. In the rat proximal femoral epiphysis, ossification develops from the medullary circulation of the diaphysis, quickly extending to the neck and the base of the head. Hypertrophic chondrocytes occupy the epiphyseal cartilage, and a physeal plate with regular cell columns is present. Starting from about the end of the third month one or more points of fibrovascular outgrowth, above the physeal line, can be observed in each sample. They are often placed centrally or, sometimes, peripherally. The fibrovascular outgrowths penetrate deeply into the cartilage and extend laterally. At age 8 mo, large fibro-osseous peduncles connect the epiphysis to the diaphyseal tissue. At 12 mo, the entire epiphysis appears calcified with an almost total absence of residual cartilage islands. This situation differs in man and in other mammals due both to differing thickness of the cartilage and to the presence of more extensive sources of blood vessels other than the diaphyseal microcirculation, as supplied by the teres ligament and Hunter's circle. In young rats, subchondral vessels and the synovial fluid could play a role in feeding the ossifying cartilage. Later, a loss of resistance of the physis due to marked degeneration of the cell columns, and extensive chondrocyte hypertrophy permit fibrovascular penetration starting from diaphyseal vessels rather than neighbouring vascular territories, such as

  14. 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

  15. Effects of caffeine and nicotine administration on growth and ossification of the ICR mouse fetus.

    PubMed

    Leblebicioglu-Bekcioglu, B; Paulson, R B; Paulson, J O; Sucheston, M E; Shanfeld, J; Bradway, S D

    1995-01-01

    The objective of this study was to determine how fetal effects are altered when nicotine (N) and caffeine (CA) are administered concurrently at dosages that individually produce minimal effects to the fetus. Female ICR mice were bred overnight and were assigned to four groups: CA (125 mg/kg), N (12mg/kg), CA plus N (125 mg/kg plus 12 mg/kg, respectively) treated, and control (distilled water) groups. Dams were intubated with these dosages three times daily during gestational days (GD) 6-18 and were euthanized on GD 18. Live fetuses were sexed, weighed, and examined for external malformations. One-half of the fetuses were fixed in 10% formalin and examined for internal malformations using Wilson's method. The remaining half was fixed in 95% ethanol (ETOH), stained, and cleared (Inouye's method) for skeletal examinations. Ossification was assessed by staging and measuring craniofacial bones, and counting ossification centra in sternbrae and in cervical and sacrococcygeal vertebrae. Data were analyzed by analysis of variance (ANOVA) followed by Student-Newman-Keuls post-hoc tests set at p < .05 significance level. The litter was used as the unit of measure and the ANOVA main effects were CA, N, and an interaction term (CA+N). In comparison to controls, CA treatment resulted in reduced bone measurements or reduced ossification scores in 5 of the 19 parameters examined, whereas for N only five parameters were significant. The main effects for interaction of CA+N were significant for seven parameters measured. Although it is difficult to assign the specific type of drug interaction that occurred because results were not completely consistent for all parameters measured, it may be concluded that in most parameters measured both CA and CA+N were different from controls, but CA was not different from CA+N. Under the experimental conditions of this study, we found that of the two drugs, caffeine had a significantly greater effect on fetal growth and ossification than

  16. ADAM17 controls endochondral ossification by regulating terminal differentiation of chondrocytes.

    PubMed

    Hall, Katherine C; Hill, Daniel; Otero, Miguel; Plumb, Darren A; Froemel, Dara; Dragomir, Cecilia L; Maretzky, Thorsten; Boskey, Adele; Crawford, Howard C; Selleri, Licia; Goldring, Mary B; Blobel, Carl P

    2013-08-01

    Endochondral ossification is a highly regulated process that relies on properly orchestrated cell-cell interactions in the developing growth plate. This study is focused on understanding the role of a crucial regulator of cell-cell interactions, the membrane-anchored metalloproteinase ADAM17, in endochondral ossification. ADAM17 releases growth factors, cytokines, and other membrane proteins from cells and is essential for epidermal growth factor receptor (EGFR) signaling and for processing tumor necrosis factor alpha. Here, we report that mice lacking ADAM17 in chondrocytes (A17ΔCh) have a significantly expanded zone of hypertrophic chondrocytes in the growth plate and retarded growth of long bones. This abnormality is caused by an accumulation of the most terminally differentiated type of chondrocytes that produces a calcified matrix. Inactivation of ADAM17 in osteoclasts or endothelial cells does not affect the zone of hypertrophic chondrocytes, suggesting that the main role of ADAM17 in the growth plate is in chondrocytes. This notion is further supported by in vitro experiments showing enhanced hypertrophic differentiation of primary chondrocytes lacking Adam17. The enlarged zone of hypertrophic chondrocytes in A17ΔCh mice resembles that described in mice with mutant EGFR signaling or lack of its ligand transforming growth factor α (TGFα), suggesting that ADAM17 regulates terminal differentiation of chondrocytes during endochondral ossification by activating the TGFα/EGFR signaling axis.

  17. Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus

    PubMed Central

    Matsuo, Koichi; Kuroda, Yukiko; Nango, Nobuhito; Shimoda, Kouji; Kubota, Yoshiaki; Ema, Masatsugu; Bakiri, Latifa; Wagner, Erwin F.; Takeda, Yoshihiro; Yashiro, Wataru; Momose, Atsushi

    2015-01-01

    Endochondral ossification is a developmental process by which cartilage is replaced by bone. Terminally differentiated hypertrophic chondrocytes are calcified, vascularized, and removed by chondroclasts before bone matrix is laid down by osteoblasts. In mammals, the malleus is one of three auditory ossicles that transmit vibrations of the tympanic membrane to the inner ear. The malleus is formed from a cartilaginous precursor without growth plate involvement, but little is known about how bones of this type undergo endochondral ossification. Here, we demonstrate that in the processus brevis of the malleus, clusters of osteoblasts surrounding the capillary loop produce bone matrix, causing the volume of the capillary lumen to decrease rapidly in post-weaning mice. Synchrotron X-ray tomographic microscopy revealed a concentric, cylindrical arrangement of osteocyte lacunae along capillaries, indicative of pericapillary bone formation. Moreover, we report that overexpression of Fosl1, which encodes a component of the AP-1 transcription factor complex, in osteoblasts significantly blocked malleal capillary narrowing. These data suggest that osteoblast/endothelial cell interactions control growth plate-free endochondral ossification through ‘osteogenic capillaries’ in a Fosl1-regulated manner. PMID:26428006

  18. Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects

    PubMed Central

    Ma, Pan; Yan, Wenjuan; Tian, Ye; Wang, Jingya; Feng, Jian Q.; Qin, Chunlin; Cheng, Yi-Shing Lisa; Wang, Xiaofang

    2016-01-01

    During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20Bfl/fl mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling. PMID:27405802

  19. Triceps tendon avulsion: a case report and discussion about the olecranon ossification nucleus.

    PubMed

    Naito, Kiyohito; Homma, Yasuhiro; Morita, Mamoru; Mogami, Atsuhiko; Obayashi, Osamu

    2013-11-01

    Rupture of the triceps tendon is a rare condition. We report a case of triceps tendon rupture with avulsion fracture of the olecranon with discussion about pathogenesis from the viewpoint of healing of the olecranon ossification nucleus. An 18-year-old man presented with avulsion fracture of the olecranon and triceps tendon rupture. Operative treatment was conducted with good results. Rupture of the triceps tendon is a rare injury comprising approximately 2% of all tendon injuries, and avulsion at insertion into the olecranon is the most common site of rupture. This injury is most likely to happen in young people as sports-related trauma. Among young people who have insufficient healing of the olecranon ossification nucleus, avulsion fracture of the olecranon may occur due to strong contraction force of the triceps tendon. Our clinical evidence may suggest that avulsion fracture of the olecranon is related in olecranon ossification center healing. Most triceps tendon ruptures are accompanied by avulsion fracture of the olecranon, and it is important to suspect this injury when radiographs show a small fleck of bone avulsed from the olecranon.

  20. Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification

    PubMed Central

    MacRae, Vicky E.; Farquharson, Colin

    2016-01-01

    The fundamental process of endochondral ossification is under tight regulation in the healthy individual so as to prevent disturbed development and/or longitudinal bone growth. As such, it is imperative that we further our understanding of the underpinning molecular mechanisms involved in such disorders so as to provide advances towards human and animal patient benefit. The mouse metatarsal organ explant culture is a highly physiological ex vivo model for studying endochondral ossification and bone growth as the growth rate of the bones in culture mimic that observed in vivo. Uniquely, the metatarsal organ culture allows the examination of chondrocytes in different phases of chondrogenesis and maintains cell-cell and cell-matrix interactions, therefore providing conditions closer to the in vivo situation than cells in monolayer or 3D culture. This protocol describes in detail the intricate dissection of embryonic metatarsals from the hind limb of E15 murine embryos and the subsequent analyses that can be performed in order to examine endochondral ossification and longitudinal bone growth. PMID:28060328

  1. The ossification diathesis in the Medici family: DISH and other features.

    PubMed

    Weisz, George M; Matucci-Cerinic, Marco; Lippi, Donatella; Albury, William R

    2011-12-01

    The Medici family ruled Florence for most of the period from the 1430s to the 1730s, with the senior (primogenito) branch predominating until the line ended in the 1530s and the cadet (secondogenito) branch predominating thereafter. Recent studies have identified a familial syndrome consisting of cutaneous symptoms, peripheral arthropathy and spinal ankylosis in the primogenito branch of the family, and the presence of diffuse idiopathic skeletal hyperostosis (DISH) in two members of the secondogenito branch. These findings raise the question of whether DISH was also a component of the primogenito familial syndrome. The present study provides a further specification of the ossification diathesis in the familial syndrome of the primogenito branch of the Medici family. Recently discovered photographs of exhumed Medici skeletons from the primogenito line are examined, with a focus on spinal, sacro-iliac and peripheral ossifications. These observations are supplemented with published reports of radiological, histological and macroscopic studies of the skeletons. Our interpretations of the ossification data relating to the primogenito branch of the Medici family are supportive of a diagnosis of DISH. DISH was one component of the triple pathology identified as a syndrome in the fifteenth century primogenito Medici line. As a diagnosis of DISH has recently been proposed for two sixteenth century members of the secondogenito branch of the family, it appears that the same condition affected both branches of the Medici lineage, without excluding other forms of undifferentiated joint and spondylarthropathies.

  2. 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.

  3. Uterine Rupture with Cesarean Scar Heterotopic Pregnancy with Survival of the Intrauterine Twin

    PubMed Central

    Behrman, Eric R.; Bembry, James S.; Kovac, Christine M.

    2016-01-01

    Background. Heterotopic pregnancy is a multiple gestation with both intrauterine and ectopic fetuses. A cesarean scar ectopic pregnancy is when the fetus has implanted over the previous hysterotomy site. A known complication of cesarean scar ectopic pregnancy is uterine rupture, which can cause great morbidity and mortality. Case. 28-year-old G5P3105 at 10 weeks with a dichorionic diamniotic gestation was found to have a ruptured uterus with expulsion of a cesarean scar ectopic pregnancy and retention of the intrauterine fetus. After uterine repair, the singleton gestation reached viability was delivered by emergent cesarean section for placental abruption. Conclusion. Safe management of cesarean ectopic pregnancy requires early diagnosis by ultrasonography. With early detection, management can focus on preventing maternal morbidity of uterine rupture and life-threatening hemorrhage. PMID:28116191

  4. [Heterotopic pancreas as a cause of intussusception: first case reported in Peru].

    PubMed

    Bazán Zender, Carlos; Reyes Coloma, Luis; León Cueto, José Luis; Revoredo Palacios, Giancarlo; Arias Stella Castillo, Javier; Pezo, Alonso

    2015-01-01

    The heterotopic pancreas (HP) is a rare condition in the pediatric population. HP cases involving an ileal intussusception are rare in children and very rarely reported, usually presenting with symptoms of intestinal obstruction. We report the case of a one year old male patient with a chronic history of anorexia, irritability, abdominal pain, accompanied by intermittent episodes of "currant jelly" stools that evolved to rectal bleeding. The patient presented a concomitant diagnosis of allergic colitis, which prolonged the effective surgical treatment at an external health center. In the abdominal CT scan, the classic "target" sign was found. In the exploratory laparotomy an ileoileal intussusception was confirmed, a mass was found that the histopathology laboratory confirmed as HP. To our knowledge, it is the first case of pediatric intussusception by HP reported in Peru.

  5. New technique to protect ovarian function before pelvic irradiation. Heterotopic ovarian autotransplantation

    SciTech Connect

    Leporrier, M.; von Theobald, P.; Roffe, J.L.; Muller, G.

    1987-11-01

    The authors describe a new technique for the subcutaneous heterotopic transplantation of the ovary before pelvic irradiation to treat Hodgkin's disease. Creation of a cavity to receive the transplant and the use of two surgical teams and the surgical microscope during the operation ensured its successful outcome. The transplanted ovary was followed up clinically and by ultrasound monitoring: ovarian cycles remained regular despite radiotherapy, and follicle growth occurred normally. In comparison to other types of oophoropexy described in the literature, the advantages of this technique included total protection of the ovary from irradiation, and conservation of ovarian function and fertility. One year after the procedure, puncture of the ovarian compartment produced a mature oocyte specimen.

  6. Respiratory distress associated with heterotopic gastrointestinal cysts of the oral cavity: A case report.

    PubMed

    Méndez Sáenz, Marco Antonio; de Jesús Villegas González, Mario; Ponce Camacho, Marco A; Cavazos Cavazos, Lucia M; Ibarra, Bárbara Sáenz; Esquivel García, Blanca I; Treviño González, José Luis

    2016-12-01

    Heterotopic gastrointestinal cysts of the oral cavity are benign lesions usually discovered during infancy. Their pathogenesis is not very clear. They are rare congenital anomalies that result from remnants of foregut-derived epithelium in the head, neck, thorax or abdomen during embryonic development. The majority of these lesions occur in the anterior ventral surface of the tongue and extend to the floor of the mouth. They are confused clinically by surgeons in cases of head and neck masses in children as ranulas, dermoid and thyroglossal cysts, and lymphangioma. We report the case of a 28-day newborn with a 3.6 cm oval mass on the floor of the mouth causing difficulty eating and cyanosis during crying. Complete surgical excision was performed by an oral approach under general anesthesia. Microscopic examination revealed gastric epithelium with tall columnar mucous cells on the surface and numerous short closed crypts, resembling fundal glands and mature gastric epithelium.

  7. Heterotopic gastric mucosa of the anus: a case report and review of the literature.

    PubMed

    Steele, Scott R; Mullenix, Philip S; Martin, Matthew J; Ormseth, Eric; Weppler, Eric; Graham, James; Place, Ronald J

    2004-08-01

    Ectopic gastric mucosa has been described at various locations of the body, including all levels of the gastrointestinal tract. However, this finding is rare in the rectum and anus, with 38 reported cases. In only six cases, including the present one, has the heterotopic tissue been located within 2 cm of the dentate line. We report a case of gastric heterotopia discovered in a 21-year-old male who presented with anal pain and pruritus. Flexible sigmoidoscopy demonstrated an anal polyp, and biopsy confirmed fundic-type gastric tissue. A (99m)technetium-pertechnetate scan confirmed increased uptake in the anus. After minimal clinical improvement with proton-pump inhibitors, the patient underwent local surgical excision and remains symptom-free at a follow-up of 9 months. We review the potential etiologies, clinical manifestations, treatment options, and patient outcomes.

  8. Trauma induced heterotopic bone formation and the role of the immune system: A Review

    PubMed Central

    Kraft, Casey T.; Agarwal, Shailesh; Ranganathan, Kavitha; Wong, Victor W.; Loder, Shawn; Li, John; Delano, Matthew J.; Levi, Benjamin

    2015-01-01

    Extremity trauma, spinal cord injuries, head injuries and burn injuries place patients at high risk of pathologic extraskeletal bone formation. This heterotopic bone causes severe pain, deformities and joint contractures. The immune system has been increasingly implicated in this debilitating condition. This review summarizes the various roles immune cells and inflammation play in the formation of ectopic bone, and highlights potential areas of future investigation and treatment. Cell types in both the innate and adaptive immune system such as neutrophils, macrophages, mast cells, B cells and T cells have all been implicated as having a role in ectopic bone formation through various mechanisms. Many of these cell types are promising areas of therapeutic investigation for potential treatment. The immune system has also been known to also influence osteoclastogenesis, which is heavily involved in ectopic bone formation. Chronic inflammation is also known to have an inhibitory role in the formation of ectopic bone, whereas acute inflammation is necessary for ectopic bone formation. PMID:26491794

  9. Heterotopic and orthotopic autologous chondrocyte implantation using a minipig chondral defect model.

    PubMed

    Lohan, Anke; Marzahn, Ulrike; El Sayed, Karym; Bock, Christopher; Haisch, Andreas; Kohl, Benjamin; Stoelzel, Katharina; John, Thilo; Ertel, Wolfgang; Schulze-Tanzil, Gundula

    2013-10-01

    Implantation of non-articular (heterotopic) chondrocyte-based implants might be an alternative approach to articular cartilage repair. This strategy could be helpful in cases in which there are no or too few articular chondrocytes available. Therefore, this study was undertaken to compare joint cartilage defect healing in the minipig model after implantation of heterotopic auricular and orthotopic articular chondrocytes. Poly-glycolic acid (PGA) associated three-dimensional (3D) constructs were prepared culturing autologous minipig-derived articular and auricular chondrocytes for 7 days in a dynamic culture system. Chondrocyte PGA constructs were implanted into 8mm diameter and ∼1.1mm deep chondral defects within the medial and lateral condyles of the minipig knee joints. Empty defects served as controls for assessment of the intrinsic healing response. Defect healing was monitored 6 months post implantation using a macroscopic and microscopic score system and biomechanical analysis. Neo-cartilage formation could be observed in the PGA constructs seeded with articular and auricular chondrocytes in vivo. The defect healing did not significantly differ at the macroscopic and histological level in response to implantation of either autologous articular or auricular chondrocytes seeded constructs compared with the empty defects. Although the differences were not significant, the auricular chondrocytes-based implants led to a slightly inferior repair quality at the macroscopic level, but a histologically superior healing response when compared with the empty defect group. However, biomechanical analysis revealed a higher stiffness in repair tissues produced by auricular chondrocyte implantation compared with the other groups. Deduced from these results, articular chondrocytes represent the preferable cell source for implantation. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. [Heterotopic pancreas in the gallbladder. Diagnosis, therapy, and course of a rare developmental anomaly of the pancreas].

    PubMed

    Neupert, G; Appel, P; Braun, S; Tonus, C

    2007-03-01

    Ectopic pancreas is a rare entity but the second most prevalent pancreatic anomaly. Heterotopic pancreas is defined as the presence of pancreatic tissue without any anatomic or vascular continuity with the main body of the pancreas. Its aetiology is not clearly established. In 1916, Poppi published for the first time evidence of heterotopic pancreas in the gallbladder. A review of the literature up to the present showed only 28 more cases worldwide of ectopic pancreas in the gallbladder. Aberrant pancreas is incidentally discovered in 2% of autopsies and has been estimated to occur once in every 500 upper abdominal explorations. Ninety per cent of ectopic pancreas is found in the stomach, duodenum, and jejunum. Mostly it is asymptomatic and benign. For this reason, therapy is indicated only in patients with symptoms such as pyloric obstruction, bleeding, and malignant transformation. Surgical resection or endoscopic mucosal resection as a newer method are recommended.

  11. The Clinical Significance of Ossification of Ligamentum Nuchae in Simple Lateral Radiograph : A Correlation with Cervical Ossification of Posterior Longitudinal Ligament

    PubMed Central

    Kim, Duk-Gyu; Eun, Jong-Pil

    2015-01-01

    Objective Ossification of the ligamentum nuchae (OLN) is usually asymptomatic and incidentally observed in cervical lateral radiographs. Previous literatures reported the correlation between OLN and cervical spondylosis. The purpose of this study was to elucidate the clinical significance of OLN with relation to cervical ossification of posterior longitudinal ligament (OPLL). Methods We retrospectively compared the prevalence of OPLL in 105 patients with OLN and without OLN and compared the prevalence of OLN in 105 patients with OPLL and without OPLL. We also analyzed the relationship between the morphology of OLN and involved OPLL level. The OPLL level was classified as short (1-3) or long (4-6), and the morphologic subtype of OLN was categorized as round, rod, or segmented. Results The prevalence of OPLL was significantly higher in the patients with OLN (64.7%) than without OLN (16.1%) (p=0.0001). And the prevalence of OLN was also higher in the patients with OPLL (54.2%) than without OPLL (29.5%) (p=0.0002). In patients with round type OLN, 5 of 26 (19.2%) showed long level OPLL, while in patients with larger type (rod and segmented) OLN, 22 of 42 (52.3%) showed long level OPLL (p=0.01). Conclusion There was significant relationship between OLN and OPLL prevalence. This correlation indicates that there might be common systemic causes as well as mechanical causes in the formation of OPLL and OLN. The incidentally detected OLN in cervical lateral radiograph, especially larger type, might be helpful to predict the possibility of cervical OPLL. PMID:26713144

  12. 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

  13. Special pattern of endochondral ossification in human laryngeal cartilages: X-ray and light-microscopic studies on thyroid cartilage.

    PubMed

    Claassen, Horst; Schicht, Martin; Sel, Saadettin; Paulsen, Friedrich

    2014-04-01

    Endochondral ossification is a process that also occurs in the skeleton of the larynx. Differences in the ossification mechanism in comparison to growth plates are not understood until now. To get deeper insights into this process, human thyroid cartilage was investigated by the use of X-rays and a series of light-microscopic stainings. A statistical analysis of mineralization was done by scanning areas of mineralized cartilage and of ossification. We detected a special mode of endochondral ossification which differs from the processes in growth plates. Thyroid cartilage ossifies very slowly and in a gender-specific manner. Compared with age-matched women, bone formation in thyroid cartilage of men is significantly higher in the age group 41-60 years. Endochondral ossification is prepared by internal changes of extracellular matrix leading to areas of asbestoid fibers with ingrowing cartilage canals. In contrast to growth plates, bone is deposited on large areas of mineralized cartilage, which appear at the rims of cartilage canals. Furthermore, primary parallel fibered bone was observed which was deposited on woven bone. The predominant bone type is cancellous bone with trabeculae, whereas compact bone with Haversian systems was seldom found. Trabeculae contain a great number of reversal and arresting lines meaning that the former were often reconstructed and that bone formation was arrested and resumed again with advancing age. It is hypothesized that throughout life trabeculae of ossified thyroid cartilage undergo adaptation to different loads due to the use of voice.

  14. Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.

    PubMed

    Schottler, F; Couture, D; Rao, A; Kahn, H; Lee, K S

    1998-05-25

    Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

  15. Patterns of postcranial ossification and sequence heterochrony in bats: life histories and developmental trade-offs.

    PubMed

    Koyabu, Daisuke; Son, Nguyen Truong

    2014-12-01

    The recently increased interest in studies on sequence heterochrony has uncovered developmental variation between species. However, how changes in developmental program are related to shifts in life-history parameters remains largely unsolved. Here we provide the most comprehensive data to date on postcranial ossification sequence of bats and compare them to various boreoeutherian mammals with different locomotive modes. Given that bats are equipped with an elongated manus, we expected to detect characteristic heterochronies particularly related to wing development. Although heterochronies related to wing development were confirmed as predicted, unexpected heterochronies regarding the pedal digits were also found. The timing of ossification onset of pedal phalanges is earlier than other mammals. Particularly, bats deviate from others in that pedal phalanges initiate ossification earlier than manual phalanges. It is known that the foot size of new born bats is close to that of adults, and that it takes several weeks to month until the wing is developed for flight. Given that the foot is required to be firm and stable enough at the time of birth to allow continued attachment to the mother and/or cave walls, we suggest that the accelerated development of the hind foot is linked to their unique life history. Since the forelimb is not mature enough for flight at birth and requires extended postnatal time to be large enough to be fully functional, we postulate that bats invest in earlier development of the hindlimb. We conclud that energy allocation trade-offs can play a significant role in shaping the evolution of development.

  16. Drug therapy targeting pyrophosphate slows the ossification of spinal ligaments in twy mice.

    PubMed

    Hiratsuka, Shigeto; Takahata, Masahiko; Shimizu, Tomohiro; Hamano, Hiroki; Ota, Masahiro; Sato, Dai; Iwasaki, Norimasa

    2017-09-20

    The lack of an effective drug therapy against ossification of spinal ligament (OSL) warrants investigation into the therapeutic target of this disease. An endogenous inhibitor of biomineralization, pyrophosphate (PPi) is a potential therapy for ectopic ossification; however, exogenous PPi is rapidly hydrolyzed by tissue non-specific alkaline phosphatase (TNAP) present in body fluids. In this study, we examined whether a drug therapy targeting PPi is efficacious for the treatment of OSL using the Enpp1(ttw/ttw) (twy) mouse model. Twenty male twy mice were randomized into four groups: 1) vehicle (Control), 2) alkaline phosphatase inhibitor levamisole (5 mg/kg/day sc continuously), 3) levamisole + exogenous PPi (160 μmol/kg/day sc continuously), and 4) nuclear retinoic acid receptor-γ (RARγ) agonist (6 μg/kg sc daily). The RARγ agonist, which is a proven inhibitor of ectopic endochondral ossification, was used as a positive control. Treatments commenced when the mice were 5 weeks of age and continued for 4 weeks. Longitudinal micro-computed tomography and postmortem histological analysis were performed. Administration of levamisole alone and in combination with PPi increased serum PPi concentration by 17% and 52%, respectively, compared to that in vehicle-treated mice. The development of OSL in twy mice was suppressed by levamisole + PPi and RARγ agonist treatments, but not by levamisole alone. The levamisole + PPi therapy did not cause osteoporosis, whereas RARγ agonist-treated mice developed osteoporosis. Treatment of twy mice with levamisole in combination with exogenous PPi increased serum PPi level, which slowed the progression of OSL without producing adverse effect on bone. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. 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

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

    PubMed

    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

    2015-11-01

    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

  19. [Updates on ossification of posterior longitudinal ligament. Epidemiology and pathogenesis of OPLL].

    PubMed

    Matsunaga, Shunji

    2009-10-01

    The study aimed for epidemiology and pathogenesis of ossification of the posterior longitudinal ligament of the cervical spine (OPLL) has been continued by The Investigation Committee of Japanese Ministry of Health, Labour and Welfare till now. As a result, the number of patients and frequency in Japan were clarified, and the epidemiology in foreign countries came to be reported, too. The association of various factors to development of OPLL was reported, but a hereditary factor is most important as the pathogenesis of OPLL. Genetic analysis with participation of all Japan research institutes has started t and it is expected to elucidate pathogenic gene of OPLL in the near future.

  20. Diffuse pulmonary ossification as a rare cause of interstitial lung disease.

    PubMed

    Burkett, Andrew; Coffey, Niamh; Voduc, Nha

    2014-01-01

    Diffuse pulmonary ossification (DPO) is a rare form of interstitial lung disease. The present article describes a case of DPO in an elderly man who presented with progressive dyspnea on exertion and an isolated reduction in diffusing capacity for carbon monoxide. DPO may occur as sequelae of mitral stenosis, left heart failure, idiopathic pulmonary fibrosis, recurrent aspiration pneumonia, solid organ transplant, adult respiratory distress syndrome or may arise idiopathically. In the absence of other findings of interstitial lung disease, a lung biopsy is unlikely to be helpful in the management of these patients.

  1. Genomic study of ossification of the posterior longitudinal ligament of the spine

    PubMed Central

    IKEGAWA, Shiro

    2014-01-01

    Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common disease after the middle age. OPLL frequently causes serious neurological problems due to compression of the spinal cord and/or nerve roots. OPLL occurs in patients with monogenic metabolic diseases including rickets/osteomalacia and hypoparathyroidism; however most of OPLL is idiopathic and is considered as a multi-factorial (polygenic) disease influenced by genetic and environmental factors. Genomic studies for the genetic factors of OPLL have been conducted, mainly in Japan, including linkage and association studies. This paper reviews the recent progress in the genomic study of OPLL and comments on its future direction. PMID:25504229

  2. Optimising magnetic resonance imaging-based evaluation of the ossification of the medial clavicular epiphysis: a multi-centre study.

    PubMed

    Schmidt, S; Henke, C A; Wittschieber, D; Vieth, V; Bajanowski, T; Ramsthaler, F; Püschel, K; Pfeiffer, H; Schmeling, A; Schulz, R

    2016-11-01

    Evaluation of the ossification of the medial clavicular epiphysis plays a key role in forensic age estimation, particularly in determining whether the age of 18 has been attained. A key research objective in the forensic age estimation field at present is to establish non-X-ray methods for investigating the clavicle. This paper looks at the use of magnetic resonance imaging for evaluating the developmental state of the medial clavicular epiphysis. Clavicle specimens obtained from autopsies of 125 female and 270 male subjects aged from 10 to 30 were examined using a 3-T magnetic resonance scanner. One FFE-3D-T1 gradient echo sequence and one 2D-T2 turbo spin echo sequence were acquired. In each case, two investigators undertook a consensual determination of the ossification stage of the medial clavicular epiphysis using recognised classification systems. To determine intra-observer and inter-observer agreement, 80 clavicle specimens were subjected to repeat evaluation. We present statistics relating to the ossification stages. The inclusion of established sub-stages of clavicular ossification offers an additional option for determining whether a subject has attained the age of 18 which is applicable in both sexes. For both sexes, the minimum ages for ossification stages 4 and 5 allow conclusions to be drawn about a subject's age at a point in time lying several years in the past. Magnetic resonance imaging is a valid investigatory procedure for determining the ossification stage of the medial clavicular epiphysis. This paper makes a contribution to expanding the range of methods available for forensic age estimation.

  3. Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

    PubMed Central

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  4. [Heterotopic osteogenesis of autogenous marrow stromal cells on ceramic bovine bone/ hydrogel scaffold].

    PubMed

    He, Dawei; Jin, Yan; Luo, Kai; Li, Shibao

    2006-02-01

    To observe the heterotopic osteogenesis of the autogenous marrow stromal cells (MSCs) on the ceramic bovine bone (CBB)/hydrogel scaffold (HG) and the effects of the recombinant human bone morphogenetic protein-2 (rhBMP-2) and the transforming growth factor beta (TGF-beta) on osteogenesis. The autogenous marrow stromal cells were cultured by the mineralized condition medium (10% FBS, dexamethasone 10 nmol, L-vitamin C 50 mg/L, beta-sodium glycerophosphate DMEM culture medium 10 mmol). At 5 days, the MSCs differentiation was observed by Type I collagen, the Mend calcium-cobalt staining, and the Von-Kossa staining. The cell suspension of 5 x 10(6)/ml was obtained. There were three groups: Group A: added in rhBMP-2 (10 microg)-TGF-beta (0.05 microg); Group B: added in TGF-beta (0.05 microg); and Group C (the control group): without the growth factor. Then, the MSCs loading on CBB/HG were embedded in the autogenous subcutaneous area at 4 and 8 weeks, and the osteogenesis was observed by the HE staining and the modified Mallory's trichrome staining, with an image analysis. Type I collagen and the bone morphogenetic synthesis were examined by the immunohistochemistry stains. Most MSCs induced by the mineralized condition medium at 5 days became smaller and polygon-shaped, and the cytodendrite became shorter. The MSCs were observed by the Mend calcium-cobalt staining. Some brown and black grains were found in the cytochylema. The MSCs were positive for the Type I collagen immunohistochemistry stains. At 20 days, the mineralized nubs were found by the Von Kossas stains. At 4 weeks, some strips of the new bone were observed by the HE staining and the modified Mallory's trichrome staining in all the groups. The bone matrix area was significantly larger in Group A than in Group B(P < 0.01). The average gray degrees of Type I collagen were lower in Groups A and B than in Group C. However, there was no significant difference in the bone morphogenesis among the three groups. At 8

  5. Use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement

    SciTech Connect

    Sylvester, J.E.; Greenberg, P.; Selch, M.T.; Thomas, B.J.; Amstutz, H.

    1988-03-01

    Formation of heterotopic bone (HTB) following total hip replacement may partially or completely ankylose the joint space, causing pain and/or limiting the range of motion. Patients at high risk for formation of HTB postoperatively include those with previous HTB formation, heterotopic osteoarthritis, and active rheumatoid spondylitis. Patients in these high risk groups have a 63-69% incidence of post-operative HTB formation, usually seen radiographically by 2 months post-operation. From 1980-1986 twenty-nine hips in 28 consecutively treated patients were irradiated post-operatively at the UCLA Center for the Health Sciences. The indication for irradiation was documented HTB formation previously in 26 of the 27 hips presented below. From 1980-1982 patients received 20 Gray (Gy) in 2 Gy fractions; from 1982-1986 the dose was reduced to 10 Gy in 2 Gy fractions. Twenty-seven hips in 26 patients completed therapy and were available for evaluation, with a minimum of 2 month follow-up, and a median follow-up of 12 months. Three of 27 hips developed significant HTB (Brooker grade III or IV) post-operatively, whereas 5 of 27 hips developed minor, nonsymptomatic HTB (Brooker grade I). When irradiation was begun by postoperative day 4, 0 of 17 hips formed significant HTB. If irradiation began after post-operative day 4, 3 of 10 hips formed significant HTB (Brooker grade III or IV). These 3 hips received doses of 10 Gy in one hip and 20 Gy in the other 2 hips. There were no differences in the incidence or severity of side effects in the 10 Gy vs. the 20 Gy treatment groups. Eighteen hips received 10 Gy, 8 hips 20 Gy and, 1 hip 12 Gy. In conclusion, 10 Gy in 5 fractions appears as effective as 20 Gy in 10 fractions at preventing post-operative formation of HTB. For optimal results, treatment should begin as early as possible prior to post-operative day 4.

  6. Complex Evolutionary and Genetic Patterns Characterize the Loss of Scleral Ossification in the Blind Cavefish Astyanax mexicanus

    PubMed Central

    O’Quin, Kelly E.; Doshi, Pooja; Lyon, Anastasia; Hoenemeyer, Emma; Yoshizawa, Masato; Jeffery, William R.

    2015-01-01

    The sclera is the tough outer covering of the eye that provides structural support and helps maintain intraocular pressure. In some fishes, reptiles, and birds, the sclera is reinforced with an additional ring of hyaline cartilage or bone that forms from scleral ossicles. Currently, the evolutionary and genetic basis of scleral ossification is poorly understood, especially in teleost fishes. We assessed scleral ossification among several groups of the Mexican tetra (Astyanax mexicanus), which exhibit both an eyed and eyeless morph. Although eyed Astyanax surface fish have bony sclera similar to other teleosts, the ossicles of blind Astyanax cavefish generally do not form. We first sampled cavefish from multiple independent populations and used ancestral character state reconstructions to determine how many times scleral ossification has been lost. We then confirmed these results by assessing complementation of scleral ossification among the F1 hybrid progeny of two cavefish populations. Finally, we quantified the number of scleral ossicles present among the F2 hybrid progeny of a cross between surface fish and cavefish, and used this information to identify quantitative trait loci (QTL) responsible for this trait. Our results indicate that the loss of scleral ossification is common–but not ubiquitous–among Astyanax cavefish, and that this trait has been convergently lost at least three times. The presence of wild-type, ossified sclera among the F1 hybrid progeny of a cross between different cavefish populations confirms the convergent evolution of this trait. However, a strongly skewed distribution of scleral ossicles found among surface fish x cavefish F2 hybrids suggests that scleral ossification is a threshold trait with a complex genetic basis. Quantitative genetic mapping identified a single QTL for scleral ossification on Astyanax linkage group 1. We estimate that the threshold for this trait is likely determined by at least three genetic factors which

  7. Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult

    PubMed Central

    Aimi, Fabio; Georgiopoulou, Stavroula; Kalus, Ina; Lehner, Fabienne; Hegglin, Alica; Limani, Përparim; Gomes de Lima, Vinicius; A. Rüegg, Markus; Hall, Michael N.; Lindenblatt, Nicole; Haas, Elvira; Battegay, Edouard J.; Humar, Rok

    2015-01-01

    To explore the general requirement of endothelial mTORC2 during embryonic and adolescent development, we knocked out the essential mTORC2 component Rictor in the mouse endothelium in the embryo, during adolescence and in endothelial cells in vitro. During embryonic development, Rictor knockout resulted in growth retardation and lethality around embryonic day 12. We detected reduced peripheral vascularization and delayed ossification of developing fingers, toes and vertebrae during this confined midgestational period. Rictor knockout did not affect viability, weight gain, and vascular development during further adolescence. However during this period, Rictor knockout prevented skin capillaries to gain larger and heterogeneously sized diameters and remodeling into tortuous vessels in response to FGF2. Rictor knockout strongly reduced extensive FGF2-induced neovascularization and prevented hemorrhage in FGF2-loaded matrigel plugs. Rictor knockout also disabled the formation of capillary-like networks by FGF2-stimulated mouse aortic endothelial cells in vitro. Low RICTOR expression was detected in quiescent, confluent mouse aortic endothelial cells, whereas high doses of FGF2 induced high RICTOR expression that was associated with strong mTORC2-specific protein kinase Cα and AKT phosphorylation. We demonstrate that the endothelial FGF-RICTOR axis is not required during endothelial quiescence, but crucial for midgestational development and sustained and extensive neovascularization in the adult. PMID:26635098

  8. Ossification of the Medial Clavicular Epiphysis on Chest Radiographs: Utility and Diagnostic Accuracy in Identifying Korean Adolescents and Young Adults under the Age of Majority

    PubMed Central

    2016-01-01

    The aim of our study was to evaluate the utility and diagnostic accuracy of the ossification grade of medial clavicular epiphysis on chest radiographs for identifying Korean adolescents and young adults under the age of majority. Overall, 1,151 patients (age, 16-30) without any systemic disease and who underwent chest radiography were included for ossification grading. Two radiologists independently classified the ossification of the medial clavicular epiphysis from chest radiographs into five grades. The age distribution and inter-observer agreement on the ossification grade were assessed. The diagnostic accuracy of the averaged ossification grades for determining whether the patient is under the age of majority was analyzed by using receiver operating characteristic (ROC) curves. Two separate inexperienced radiologists assessed the ossification grade in a subgroup of the patients after reviewing the detailed descriptions and image atlases developed for ossification grading. The median value of the ossification grades increased with increasing age (from 16 to 30 years), and the trend was best fitted by a quadratic function (R-square, 0.978). The inter-observer agreements on the ossification grade were 0.420 (right) and 0.404 (left). The area under the ROC curve (AUC) was 0.922 (95% CI, 0.902-0.942). The averaged ossification scores of 2.62 and 4.37 provided 95% specificity for a person < 19 years of age and a person ≥ 19 years of age, respectively. A preliminary assessment by inexperienced radiologists resulted in an AUC of 0.860 (95% CI, 0.740-0.981). The age of majority in Korean adolescents and young adults can be estimated using chest radiographs. PMID:27550480

  9. Ossification of the Medial Clavicular Epiphysis on Chest Radiographs: Utility and Diagnostic Accuracy in Identifying Korean Adolescents and Young Adults under the Age of Majority.

    PubMed

    Yoon, Soon Ho; Yoo, Hye Jin; Yoo, Roh Eul; Lim, Hyun Ju; Yoon, Jeong Hwa; Park, Chang Min; Lee, Sang Seob; Yoo, Seong Ho

    2016-10-01

    The aim of our study was to evaluate the utility and diagnostic accuracy of the ossification grade of medial clavicular epiphysis on chest radiographs for identifying Korean adolescents and young adults under the age of majority. Overall, 1,151 patients (age, 16-30) without any systemic disease and who underwent chest radiography were included for ossification grading. Two radiologists independently classified the ossification of the medial clavicular epiphysis from chest radiographs into five grades. The age distribution and inter-observer agreement on the ossification grade were assessed. The diagnostic accuracy of the averaged ossification grades for determining whether the patient is under the age of majority was analyzed by using receiver operating characteristic (ROC) curves. Two separate inexperienced radiologists assessed the ossification grade in a subgroup of the patients after reviewing the detailed descriptions and image atlases developed for ossification grading. The median value of the ossification grades increased with increasing age (from 16 to 30 years), and the trend was best fitted by a quadratic function (R-square, 0.978). The inter-observer agreements on the ossification grade were 0.420 (right) and 0.404 (left). The area under the ROC curve (AUC) was 0.922 (95% CI, 0.902-0.942). The averaged ossification scores of 2.62 and 4.37 provided 95% specificity for a person < 19 years of age and a person ≥ 19 years of age, respectively. A preliminary assessment by inexperienced radiologists resulted in an AUC of 0.860 (95% CI, 0.740-0.981). The age of majority in Korean adolescents and young adults can be estimated using chest radiographs.

  10. 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

  11. 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

  12. Dlx5 is a positive regulator of chondrocyte differentiation during endochondral ossification.

    PubMed

    Ferrari, Deborah; Kosher, Robert A

    2002-12-15

    The process of endochondral ossification in which the bones of the limb are formed after generation of cartilage models is dependent on a precisely regulated program of chondrocyte maturation. Here, we show that the homeobox-containing gene Dlx5 is expressed at the onset of chondrocyte maturation during the conversion of immature proliferating chondrocytes into postmitotic hypertrophying chondrocytes, a critical step in the maturation process. Moreover, retroviral misexpression of Dlx5 during differentiation of the skeletal elements of the chick limb in vivo results in the formation of severely shortened skeletal elements that contain excessive numbers of hypertrophying chondrocytes which extend into ectopic regions, including sites normally occupied by immature chondrocytes. The expansion in the extent of hypertrophic maturation detectable histologically is accompanied by expanded and upregulated domains of expression of molecular markers of chondrocyte maturation, particularly type X collagen and osteopontin, and by expansion of mineralized cartilage matrix, which is characteristic of terminal hypertrophic differentiation. Furthermore, Dlx5 misexpression markedly reduces chondrocyte proliferation concomitant with promoting hypertrophic maturation. Taken together, these results indicate that Dlx5 is a positive regulator of chondrocyte maturation and suggest that it regulates the process at least in part by promoting conversion of immature proliferating chondrocytes into hypertrophying chondrocytes. Retroviral misexpression of Dlx5 also enhances formation of periosteal bone, which is derived from the Dlx5-expressing perichondrium that surrounds the diaphyses of the cartilage models. This suggests that Dlx5 may be involved in regulating osteoblast differentiation, as well as chondrocyte maturation, during endochondral ossification.

  13. [Ultrasonography assessment of ossification foci of the wrist and pubertal growth spurt].

    PubMed

    Nessi, R; Garattini, G; Bazzini, E; Zaffaroni, R; Lazzerini, F

    1997-01-01

    High-resolution ultrasound (US) of the hand and wrist was compared with radiography in 26 young patients (mean age: 11.4 years) to be submitted to orthodontic therapy. US scans were targeted on the ossification centers critical for the growth spurt, namely the pisiform and adductor sesamoid bones of the metacarpophalangeal joint of the thumb and the cartilage of the distal phalanx of the third finger. All images were retrospectively reviewed on a double-blind basis by two independent observers who gave a conspicuity score to each structure of interest. All the scores were submitted to statistical analysis with the Wilcoxon test. US images clearly demonstrated the initial appearance of the ossification centers of the pisiform and sesamoid bones. These structures appeared as hyperechoic spots causing marked acoustic shadowing. The persistence of the phalangeal cartilage was depicted as a thin rim interrupting the hyperechoic cortical profile of the bone. US results were statistically equivalent to radiographic findings in the pisiform [p (op1) = .3105; p (op2) = .8886] and sesamoid bones of the thumb [p (op1) = .1386; p (op2) = .354]. A statistically significant difference between the two techniques was found in the third finger cartilage (p (op1) = .0277; p (op2) = .0759) because its profile was poorly depicted on some US images. To conclude, wrist US is proposed as a simple and valuable radiation-free support examination for the follow-up of skeletal maturation in adolescents to be submitted to orthodontic therapy.

  14. [The non-damaging method for the insertion of a standard electrode for cochlear ossification].

    PubMed

    Diab, Kh M; Daikhes, N A; Pashchinina, O A; Siraeva, A R; Kuznetsov, A O

    2016-01-01

    The objective of the present study was to develop the non-damaging method for the insertion of a standard electrode for cochlear ossification with a view to improving the results of hearing and speech rehabilitation of the patients presenting with grade IV sensorineural impairment of hearing. Twenty preparations of the cadaveric temporal bone were used to investigate topographic and anatomical relationships in the main structures of the middle and internal ears, viz. the second cochlear coil, vestibulum and its windows, processus cochleaformis, spiral lamina, and modiolus. The optimal method for the insertion of a standard electrode into the spiral canal of the cochlea after the removal of the ossified structures is proposed. The optimal site for constructing the second colostomy is determined that allows the spiral plate and modiolus to be maximally preserved. The proposed method was employed to treat 11 patients with grade IV sensorineural impairment of hearing and more than 5 mm ossification of the basal cochlear coil. With this method, it proved possible to insert the maximum number of electrodes into the cochlear spiral canal and thereby to obtain excellent results of hearing and speech rehabilitation in the patients with the ossified cochlea.

  15. Forensic age estimation through evaluation of the apophyseal ossification of the iliac crest in Western Chinese.

    PubMed

    Zhang, Kui; Dong, Xiao-ai; Chen, Xiao-gang; Li, Yuan; Deng, Zhen-hua

    2015-07-01

    The criminal age estimation procedures have gained greatest significance to date, a reliable age diagnostics may depend on data of skeletal maturation from different socioeconomic status. In order to establish the iliac crest apophysis as a possible criterion for forensic age estimation in a different socioeconomic status, and to examine the pace of ossification for the iliac crest apophysis in Western Chinese, one thousand seven hundreds and seventy-seven conventional pelvic radiographs relating to West China Han group routinely taken between January 2010 and June 2012 have been sighted. The data was analysed with separation of the sexes. The results indicated that stage 2a was last observed in females at the age of 17.00 and in males at the age of 18.01, stage 3a was first achieved in females at the age of 14.46 and in males at the age of 15.31, stage 4 was observed between 17.95 and 25.98 years for male and between 18.36 and 25.95 years for female. By comparison with previous studies, our research indicated that Western Chinese presents a delaying development for the iliac crest apophysis. Furthermore, the present study with eight stages of ossification for the iliac crest offers a valuable alternative method of estimation of 18 years of age for Western Chinese.

  16. Ossification of the Posterior Petroclinoid Dural Fold: A Cadaveric Study with Neurosurgical Significance

    PubMed Central

    Kimball, David; Kimball, Heather; Matusz, Petru; Tubbs, R. Shane; Loukas, Marios; Cohen-Gadol, A. Aaron

    2015-01-01

    Objectives The roof of the porus trigeminus, composed of the posterior petroclinoid dural fold, is an important landmark to the skull base surgeon. Ossification of the posterior petroclinoid dural fold is an anatomical variation rarely mentioned in the literature. Such ossification results in the trigeminal nerve traversing a bony foramen as it enters Meckel cave. The authors performed this study to better elucidate this anatomical variation. Design Fifteen adult cadaveric head halves were subjected to dissection of the middle cranial fossa. Microdissection techniques were used to examine the posterior petroclinoid dural folds. Skull base osteology was also studied in 71 dry human skulls with attention paid to the attachment point of the posterior petroclinoid dural folds at the trigeminal protuberances. Setting Cadaver laboratory Main Outcome Measures Measurements were made using a microcaliper. Digital images were made of the dissections. Results Completely ossified posterior petroclinoid folds were present in 20% of the specimens. Of the 142 dry skull sides examined, 9% had large trigeminal protuberances. Conclusions Based on this study, the posterior petroclinoid dural fold may completely ossify in adults that may lead to narrowing of the porus trigeminus and potential compression of the trigeminal nerve at the entrance to Meckel cave. PMID:26225315

  17. Thoracic myelopathy due to ossification of the yellow ligament in young baseball pitchers.

    PubMed

    Kaneyama, Shuichi; Doita, Minoru; Nishida, Kotaro; Shimomura, Takatoshi; Maeno, Koichiro; Tamura, Yuichi; Kurosaka, Masahiro; Yonenobu, Kazuo

    2008-02-01

    Case series. To report rare cases of thoracic myelopathy due to ossification of the yellow ligament (OYL) in relatively young baseball pitchers and show clinical evidence of the role of dynamic mechanical stress on the development of OYL. The pathogenesis of OYL is still unclear. The majority of cases of OYL occur in middle-aged men whereas younger people are rarely affected. This has lead to the hypothesis that diffuse mechanical stress and degenerative changes correlate with the development of OYL. However, there have been no clinical reports demonstrating the critical role of mechanical stress in the ossification. Two young highly active baseball pitchers with thoracic myelopathy due to OYL are presented. Both had no previous systemic disorders or family history of treatment for OYL. Magnetic resonance imaging and computed tomography demonstrated compression of the spinal cord by unilateral left sided OYL at the level of the thoracolumbar junction. Both patients were treated with posterior decompression. They recovered full muscle power after operation and resumed pitching training. Patients had no other factors influencing the development of OYL and the lesions were localized at the left side in the thoracolumbar junction, indicating that repeated, localized rotatory mechanical stress caused by the pitching motion probably influenced the development of OYL in these young baseball pitchers.

  18. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription

    PubMed Central

    Wang, Weiguang; Lian, Na; Li, Lingzhen; Moss, Heather E.; Wang, Weixi; Perrien, Daniel S.; Elefteriou, Florent; Yang, Xiangli

    2009-01-01

    Activating transcription factor 4 (Atf4) is a leucine-zipper-containing protein of the cAMP response element-binding protein (CREB) family. Ablation of Atf4 (Atf4−/−) in mice leads to severe skeletal defects, including delayed ossification and low bone mass, short stature and short limbs. Atf4 is expressed in proliferative and prehypertrophic growth plate chondrocytes, suggesting an autonomous function of Atf4 in chondrocytes during endochondral ossification. In Atf4−/− growth plate, the typical columnar structure of proliferative chondrocytes is disturbed. The proliferative zone is shortened, whereas the hypertrophic zone is transiently expanded. The expression of Indian hedgehog (Ihh) is markedly decreased, whereas the expression of other chondrocyte marker genes, such as type II collagen (Col2a1), PTH/PTHrP receptor (Pth1r) and type X collagen (Col10a1), is normal. Furthermore, forced expression of Atf4 in chondrocytes induces endogenous Ihh mRNA, and Atf4 directly binds to the Ihh promoter and activates its transcription. Supporting these findings, reactivation of Hh signaling pharmacologically in mouse limb explants corrects the Atf4−/− chondrocyte proliferation and short limb phenotypes. This study thus identifies Atf4 as a novel transcriptional activator of Ihh in chondrocytes that paces longitudinal bone growth by controlling growth plate chondrocyte proliferation and differentiation. PMID:19906842

  19. 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.

  20. 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

  1. Masticatory muscle tendon-aponeurosis hyperplasia exhibits heterotopic calcification in tendons.

    PubMed

    Sato, T; Hori, N; Nakamoto, N; Akita, M; Yoda, T

    2014-05-01

    Masticatory muscle tendon-aponeurosis hyperplasia is a new disease entity associated with limited mouth opening. In this study, we analyzed the microstructural characteristics of muscles and tendons in masticatory muscle tendon-aponeurosis hyperplasia by electron microscopy and energy-dispersive X-ray analysis to determine the elemental composition. Histological analysis was performed to detect the calcification. Transmission electron microscopy and scanning electron microscopy were conducted to clarify the microstructural characteristics of muscles and tendons. Energy-dispersive X-ray microanalysis was performed to identify the distribution of elements. Mineralized nodules were observed in tendon tissues of masticatory muscle tendon-aponeurosis hyperplasia as compared with facial deformity. Electron microscopy revealed that the muscle and tendon tissues in masticatory muscle tendon-aponeurosis hyperplasia showed degenerative changes and distinctive histological findings as compared with tissues in facial deformity. We found that Ca, P, and Si were detected only in masticatory muscle tendon-aponeurosis hyperplasia. We demonstrated that masticatory muscle tendon-aponeurosis hyperplasia exhibits heterotopic calcification in tendon tissues. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Risk Factors and Early Predictors for Heterotopic Pregnancy after In Vitro Fertilization

    PubMed Central

    Geng, Ling; Xia, Mingdi; Zhai, Junyu; Zhang, Wei; Zhang, Yuchao; Sun, Yinhua; Zhang, Jiangtao; Zhu, Dongyi; Zhao, Han; Chen, Zi-Jiang

    2015-01-01

    This study investigated the risk factors and early predictors for heterotopic pregnancy (HP) after in vitro fertilization and embryo transfer (IVF-ET). From January 2008 to January 2013, 41 cases of HP and 72 cases of intrauterine twin pregnancy after IVF-ET were recruited and retrospectively analyzed. Compared with intrauterine twin pregnancy group, the HP group had a lower basal luteinizing hormone (LH) level (P = 0.005) and more cases had a history of hydrosalpinx (P = 0.008). After 14 days of IVF-ET, the serum β-HCG (β-human chorionic gonadotropin), E2 (Estradiol) and P (Progesterone) levels were lower in HP group (P<0.001, respectively). Moreover, vaginal bleeding and abdominal pain were the significant features of HP before diagnosis (P<0.001, respectively). Further by logistic regression, serum β-hCG, P levels on the 14th day after ET, and vaginal bleeding were identified as the independent factors of HP. These results indicate that when two or more embryos transferred in IVF procedure, β-hCG, P levels on the 14th day after ET, and vaginal bleeding could be taken as predictors for HP. PMID:26510008

  3. Heterotopic CO2 laser stimulation inhibits tooth-related somatosensory evoked potentials.

    PubMed

    Fujii-Abe, Keiko; Oono, Yuka; Motohashi, Katsunori; Fukayama, Haruhisa; Umino, Masahiro

    2010-06-01

    The diffuse noxious inhibitory control (DNIC) effect is the neurophysiological basis for the phenomenon that heterotopic "pain inhibits pain" in remote areas of the body. The effect of DNIC is mediated by spino-bulbo-spinal loops and a final postsynaptic inhibitory mechanism. The DNIC effect depends on intensity, duration, quality, and application site of conditioning stimulation and stimulated nerve fiber-type. DNIC induced by CO(2) laser conditioning stimulation has, however, not yet been investigated, and the present study was designed to examine this. As the indicator of test stimulation, the late component of somatosensory evoked potentials (SEPs) induced by electrical tooth stimulation and pain intensity were examined under CO(2) laser conditioning stimulation. As the conditioning stimuli, CO(2) laser energy (lambda = 10.6 microm, spot size Ø = 2 mm) was applied to the dorsum of the left hand. The maximum reductions in SEP amplitude and pain intensity evaluated using a visual analog scale were 34.7% and 28.7%, respectively during CO(2) laser conditioning stimulation. No aftereffect was observed. The present study revealed that CO(2) laser radiation attenuated the late component of SEPs induced by electrical tooth stimulation, triggering the DNIC effect but with no aftereffect.

  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

  5. Paraparesis in a black man brought on by ossification of the ligamentum flavum: case report and review of the literature.

    PubMed

    Wiseman, Diana Barrett; Stokes, John K; Toselli, Richard M

    2002-12-01

    We present the second case of paraparesis secondary to ossification of the ligamentum flavum at the midthoracic region in a black man. Ossification of the ligamentum flavum is frequently described in the Japanese population where the presentation is often in the lower thoracic region. The patient is a 37-year-old black man who, over the 6 months before admission, noticed progressive paraparesis. CT myelogram revealed severe thoracic stenosis by an ossified ligamentum flavum from T4 to T7 with most severe involvement at the T5, T6, and T7 levels. The patient underwent multilevel laminectomies and medial facetectomies from T4 to T7. Over the past decade, ossification of the ligamentum flavum has been reported with increasing frequency in non-Asian patients. This is the third case report in a black man. In addition, ossification of the ligamentum flavum in this particular location is rarely reported. The increased use of advanced neuroimaging techniques in the evaluation of "back pain" may reveal that the prevalence of this condition is higher than expected in non-Asian populations. Improvement in neurologic symptoms secondary to decompressive laminectomies will depend on the degree and duration of spinal cord compression.

  6. Effect of prenatal administration of therapeutic doses of topiramate on ossification of ribs and vertebrae in rat fetuses.

    PubMed

    Fadel, R A; Sequeira, R P; Abu-Hijleh, M F; Obeidat, M; Salem, A H A

    2012-01-01

    There are few studies that have addressed the effects of prenatal exposure of topiramate on ossification of the bones derived from the paraxial mesoderm. This study aimed to evaluate skeletal ossification of ribs and vertebrae in 20-day-old rat fetuses after maternal exposure to two therapeutic doses of topiramate. Three groups of Sprague-Dawley pregnant rats were used: control, topiramate 50 mg/kg/day and topiramate 100 mg/kg/day treated groups. Topiramate was administered by gavage from day 6-19 of gestation. Fetuses were collected on day 20 by caesarean section. Fetal bones were stained with alizarin red and ossification was assessed. Results showed significant delayed ossification of ribs and vertebrae in topiramate-exposed fetuses at both doses and the effects were not dose dependent. In all examined groups, there was a direct correlation between the fetal weight and the number of complete ossified vertebral centers. Also, there were significant increases in skeletal abnormalities, particularly in ribs in both treated groups when compared to the control group. In conclusion, therapeutic doses of topiramate should be taken cautiously during pregnancy as they lead to fetal growth restriction and increases abnormalities of axial skeleton in rat fetuses.

  7. 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

  8. Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves

    PubMed Central

    Stephens, Elizabeth H.; Saltarrelli, Jerome G.; Balaoing, Liezl R.; Baggett, L. Scott; Nandi, Indrajit; Anderson, Kristin M.; Morrisett, Joel D.; Reardon, Michael J.; Simpson, Melanie A.; Weigel, Paul H.; Olmsted-Davis, Elizabeth A.; Davis, Alan R.; Grande-Allen, K. Jane

    2012-01-01

    The calcification process in aortic stenosis has garnered considerable interest but only limited investigation into selected signaling pathways. This study investigated mechanisms related to hypoxia, hyaluronan homeostasis, brown adipocytic differentiation, and ossification within calcified valves. Surgically explanted calcified aortic valves (n=14) were immunostained for markers relevant to these mechanisms and evaluated in the center (NodCtr) and edge (NodEdge) of the calcified nodule (NodCtr), tissue directly surrounding nodule (NodSurr); center and tissue surrounding small “prenodules” (PreNod, PreNodSurr); and normal fibrosa layer (CollFibr). Pearson correlations were determined between staining intensities of markers within regions. Ossification markers primarily localized to NodCtr and NodEdge, along with markers related to hyaluronan turnover and hypoxia. Markers of brown adipocytic differentiation were frequently co-localized with markers of hypoxia. In NodCtr and NodSurr, brown fat and ossification markers correlated with hyaluronidase-1, whereas these markers, as well as hypoxia, correlated with hyaluronan synthases in NodEdge. The protein product of tumor necrosis factor-α stimulated gene-6 strongly correlated with ossification markers and hyaluronidase in the regions surrounding the nodules (NodSurr, PreNodSurr). In conclusion, this study suggests roles for hyaluronan homeostasis and the promotion of hypoxia by cells demonstrating brown fat markers in calcific aortic valve disease. PMID:23017666

  9. Primitive Spindle Cell Neoplasm of Ileum with Extensive Heterotopic Cartilage, Presenting as Acute Abdomen in a 6-Day-Old Neonate.

    PubMed

    Nael, Ali; Wu, William W; Shane, Lisa; Rao, Nagesh; Zwerdling, Theodore

    2016-01-01

    Neonatal intestinal masses with spindle cell morphology have broad differential diagnoses and require a multidisciplinary approach to make the final diagnosis. Spindle cell masses with heterotopic cartilage in the gastrointestinal tract are very rare, and, to our knowledge, have not previously been reported in the neonate. Here we present a case of intestinal primitive spindle cell neoplasm with extensive heterotopic cartilage that manifested initially as acute abdomen in a 6-day-old term infant. Plain radiography demonstrated pneumoperitoneum, prompting diagnostic laparotomy that identified a perforated mass involving the midileum. Histologic and immunohistochemical examination demonstrated an infiltrative spindle cell tumor most compatible with infantile fibrosarcoma (IFS) by a process of exclusion, with nodules of mature heterotopic cartilage. Additional staging studies did not reveal any evidence of residual or metastatic disease. Recognition of this rare variant of IFS will aid in differentiation from other neonatal intestinal mesenchymal tumors.

  10. Heterotopic pancreatic tissue associated with type 1 choledochal cyst, cystolithiasis and gall bladder stones: a rare entity with review of literature.

    PubMed

    Arora, Aditi; Singh, Pradyumn; Anand, Nidhi; Husain, Nuzhat

    2017-04-10

    Choledochal cyst is a rare congenital malformation, particularly when associated with stones in cyst (cystolithiasis), gallstones and heterotopic pancreatic tissue within the cyst wall. The current case represents a 5-year-old boy with abdominal pain, pale colored stools, and jaundice. Magnetic resonance cholangiopancreatography showed a cystic lesion, arising from common bile duct with cystolithiasis and cholelithiasis. He underwent excision of choledochal cyst and gallbladder with Roux-en-Y hepaticojejunostomy. Microscopic examination showed a cyst wall composed of fibrocollagenous tissue lined by cuboidal to low columnar epithelium. The subserosal layer of cyst wall showed presence of heterotopic exocrine pancreatic tissue comprising of pancreatic acinar cells and ducts. We report the first case of heterotopic pancreatic tissue associated with choledochal cyst and cystolithiasis and cholelithiasis occurring at the same time. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Local CO2-induced swelling of shales

    NASA Astrophysics Data System (ADS)

    Pluymakers, Anne; Dysthe, Dag Kristian

    2017-04-01

    In heterogeneous shale rocks, CO2 adsorbs more strongly to organic matter than to the other components. CO2-induced swelling of organic matter has been shown in coal, which is pure carbon. The heterogeneity of the shale matrix makes an interesting case study. Can local swelling through adsorption of CO2 to organic matter induce strain in the surrounding shale matrix? Can fractures close due to CO2-induced swelling of clays and organic matter? We have developed a new generation of microfluidic high pressure cells (up to 100 bar), which can be used to study flow and adsorption phenomena at the microscale in natural geo-materials. The devices contain one transparent side and a shale sample on the other side. The shale used is the Pomeranian shale, extracted from 4 km depth in Poland. This formation is a potential target of a combined CO2-storage and gas extraction project. To answer the first question, we place the pressure cell under a Veeco NT1100 Interferometer, operated in Vertical Scanning Interferometry mode and equipped with a Through Transmissive Media objective. This allows for observation of local swelling or organic matter with nanometer vertical resolution and micrometer lateral resolution. We expose the sample to CO2 atmospheres at different pressures. Comparison of the interferometry data and using SEM-EDS maps plus optical microscopy delivers local swelling maps where we can distinguish swelling of different mineralogies. Preliminary results indicate minor local swelling of organic matter, where the total amount is both time- and pressure-dependent.

  12. Osterix regulates calcification and degradation of chondrogenic matrices through matrix metalloproteinase 13 (MMP13) expression in association with transcription factor Runx2 during endochondral ossification.

    PubMed

    Nishimura, Riko; Wakabayashi, Makoto; Hata, Kenji; Matsubara, Takuma; Honma, Shiho; Wakisaka, Satoshi; Kiyonari, Hiroshi; Shioi, Go; Yamaguchi, Akira; Tsumaki, Noriyuki; Akiyama, Haruhiko; Yoneda, Toshiyuki

    2012-09-28

    Endochondral ossification is temporally and spatially regulated by several critical transcription factors, including Sox9, Runx2, and Runx3. Although the molecular mechanisms that control the late stages of endochondral ossification (e.g. calcification) are physiologically and pathologically important, these precise regulatory mechanisms remain unclear. Here, we demonstrate that Osterix is an essential transcription factor for endochondral ossification that functions downstream of Runx2. The global and conditional Osterix-deficient mice studied here exhibited a defect of cartilage-matrix ossification and matrix vesicle formation. Importantly, Osterix deficiencies caused the arrest of endochondral ossification at the hypertrophic stage. Microarray analysis revealed that matrix metallopeptidase 13 (MMP13) is an important target of Osterix. We also showed that there exists a physical interaction between Osterix and Runx2 and that these proteins function cooperatively to induce MMP13 during chondrocyte differentiation. Most interestingly, the introduction of MMP13 stimulated the calcification of matrices in Osterix-deficient mouse limb bud cells. Our results demonstrated that Osterix was essential to endochondral ossification and revealed that the physical and functional interaction between Osterix and Runx2 were necessary for the induction of MMP13 during endochondral ossification.

  13. New patterns of the growing L3 vertebra and its 3 ossification centers in human fetuses – a CT, digital, and statistical study

    PubMed Central

    Szpinda, Michał; Baumgart, Mariusz; Szpinda, Anna; WoŸniak, Alina; Mila-Kierzenkowska, Celestyna

    2013-01-01

    Background This study describes reference data for L3 vertebra and its 3 ossification centers at varying gestational ages. Material/Methods Using CT, digital-image analysis and statistics, the growth of L3 vertebra and its 3 ossification centers in 55 spontaneously aborted human fetuses aged 17–30 weeks was examined. Results Neither sex nor right-left significant differences were found. The height and transverse and sagittal diameters of the L3 vertebral body increased logarithmically. Its cross-sectional area followed linearly, whereas its volume increased parabolically. The transverse and sagittal diameters of the ossification center of the L3 vertebral body varied logarithmically, but its cross-sectional area and volume grew linearly. The ossification center-to-vertebral body volume ratio gradually declined with age. The neural ossification centers increased logarithmically in length and width, and proportionately in cross-sectional area and volume. Conclusions With no sex differences, the growth dynamics of the L3 vertebral body follow logarithmically in height, sagittal and transverse diameters, linearly (in cross-sectional area), and parabolically (in volume). The growth dynamics of the 3 ossification centers of the L3 vertebra follow logarithmically in transverse and sagittal diameters, and linearly (in cross-sectional area and volume). The age-specific reference intervals of the L3 vertebra and its 3 ossification centers present the normative values of clinical importance in the diagnosis of congenital spinal defects. PMID:23778313

  14. Acupuncture at heterotopic acupoints facilitates distal colonic motility via activating M3 receptors and somatic afferent C-fibers in normal, constipated, or diarrhoeic rats.

    PubMed

    Gao, X; Qin, Q; Yu, X; Liu, K; Li, L; Qiao, H; Zhu, B

    2015-12-01

    Previous studies have demonstrated the efficacy of somatic stimulation for patients with gastrointestinal motility disorders. However, little effort has been made to investigate the effects of acupuncture on colonic motility, particularly in pathological conditions. The precise mechanism employed in the regulation of acupuncture on colonic motility still remains unclear. We assessed the effect of acupuncture at heterotopic acupoints on distal colonic motility using a warm-water-filled manometric balloon inserted 5-6 cm into the rectum of anesthetized normal rats or rats with diarrhea or constipation. Choline chloride, 4-DAMP, cobra venom and capsaicin were separately applied to investigate the role of M3 receptors in the regulation of distal colonic motility by acupuncture at heterotopic acupoints, and whether Aδ- and/or C-fibers are required for triggering distal colonic motility by acupuncture. Acupuncture at heterotopic acupoints increased distal colonic motility not only in normal rats but also in rats with constipation or diarrhea. M3 receptors play an important role in the facilitation of distal colonic motility triggered by acupuncture at heterotopic acupoints. Afferent nerve Aδ- and C-fibers mediate the transduction of the acupuncture signal and C-fibers are essential for enhancing the effect of acupuncture at the heterotopic acupoint on distal colonic motility. Our results reveal that acupuncture at heterotopic acupoints increases distal colonic motility regardless of normal or pathological conditions via predominately activating C-fibers of somatic afferent nerve and M3 receptors. © 2015 The Authors.Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

  15. 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

  16. 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.

  17. Central adaptation following heterotopic hand replantation probed by fMRI and effective connectivity analysis.

    PubMed

    Eickhoff, S B; Dafotakis, M; Grefkes, C; Shah, N J; Zilles, K; Piza-Katzer, H

    2008-07-01

    In this functional magnetic resonance imaging (fMRI) study, we examined changes--relative to healthy controls--in the cortical activation and connectivity patterns of two patients who had undergone unilateral heterotopic hand replantation. The study involved the patients and a group of control subjects performing visually paced hand movements with their left, right, or both hands. Changes of effective connectivity among a bilateral network of core motor regions comprising M1, lateral premotor cortex (PMC), and the supplementary motor area (SMA) were assessed using dynamic causal modelling. Both patients showed inhibition of ipsilateral PMC and SMA when moving the healthy hand, potentially indicating a suppression of inference with physiological motor execution by the hemisphere controlling the replanted hand. Moving the replanted hand, both patients showed increased activation of contralateral PMC, most likely reflecting the increased effort involved, and a pathological inhibition of the ipsilateral on the active contralateral M1 indicative of an unsuccessful modulation of the inhibitory M1-M1 balance. In one patient, M1 contralateral to the replanted hand experienced increased tonic (intrinsic connectivity) and phasic (replanted hand movement) facilitating input, whereas in the other, pathological suppression was present. These differences in effective connectivity correlated with decreased behavioural performance of the latter as assessed by kinematic analysis, and seemed to be related to earlier and more intense rehabilitative exercise commenced by the former. This study hence demonstrates the potential of functional neuroimaging to monitor plastic changes of cortical connectivity due to peripheral damage and recovery in individual patients, which may prove to be a valuable tool in understanding, evaluating and enhancing motor rehabilitation.

  18. Uterus transplantation model in sheep with heterotopic whole graft and aorta and cava anastomoses.

    PubMed

    Gonzalez-Pinto, I M; Tryphonopoulos, P; Avison, D L; Nishida, S; Tekin, A; Santiago, S; Tzakis, A G

    2013-06-01

    Uterine transplantation in the sheep model has been described as a partial or whole orthotopic graft from a living donor with vascular anastomoses. As an alternative to surrogate pregnancy or adoption uterus transplantation might be indicated for cases of infertility of uterine origin. The main complications might be rejection and thrombosis. The objective of this work was to develop a model of whole uterus transplantation that was applicable to the human setting, using grafts obtained from brain-dead donors, and suitable for immunologic and viability follow-up with a reduced risk of thrombosis. Two donors and 1 recipient were operated. The first graft was used for an anatomic study; the second was used for transplantation. The donor operation consisted of an en bloc harvest of the uterus, adnexa, and proximal vagina with the distal aorta and cava. After harvest the donor sheep was humanely killed. In the recipient ewe, heterotopic implantation was performed in the lower abdomen. An End-to-side anastomoses of aorta and cava were performed below the recipient's renal vessels. A cutaneous vaginal stoma was performed in the right lower quadrant. The recipient ewe was humanely killed for an autopsy study. The anatomy of uterine veins of the ewe differs from the human. The uterine and ovarian veins join, forming the utero-ovarian vein, which drains at the confluence of the common iliac to the cava. En bloc harvesting allows for rapid graft preparation, with vascular cuffs easily anastomosed with a low risk of thrombosis. The vaginal stoma seems appropriate to facilitate follow-up and graft biopsy. This approach can be a suitable experimental model applicable to humans using grafts from brain-dead donors.

  19. The Risk Factors and Pregnancy Outcomes of 48 Cases of Heterotopic Pregnancy from a Single Center

    PubMed Central

    2016-01-01

    The purpose of this study was to investigate risk factors that are associated with heterotopic pregnancy (HP) following in vitro fertilization (IVF)-embryo transfer (ET) and to demonstrate the outcomes of HP after the surgical treatment of ectopic pregnancies. Forty-eight patients from a single center, who were diagnosed with HP between 1998 and 2012 were included. All of the patients had received infertility treatments, such as Clomid with timed coitus (n = 1, 2.1%), superovulation with intrauterine insemination (n = 7, 14.6%), fresh non-donor IVF-ET (n = 33, 68.8%), and frozen-thawed cycles (n = 7, 14.6%). Eighty-four additional patients were randomly selected as controls from the IVF registry database. HP was diagnosed at 7.5 ± 1.2 weeks (range 5.4-10.3) gestational age. In six cases (12.5%), the diagnosis was made three weeks after the patients underwent treatment for abortion. There were significant differences in the history of ectopic pregnancy (22.5% vs. 3.6%, P = 0.002). There were no significant differences in either group between the rates of first trimester intrauterine fetal loss (15.0% vs. 13.1%) or live birth (80.0% vs. 84.1%) after the surgical treatment for ectopic pregnancy. The risk factors for HP include a history of ectopic pregnancy (OR 7.191 [1.591-32.513], P = 0.010), abortion (OR 3.948 [1.574-9.902], P = 0.003), and ovarian hyperstimulation syndrome (OHSS) (OR 10.773 [2.415-48.060], P = 0.002). In patients undergoing IVF-ET, history of ectopic pregnancy, abortion, and OHSS may be risk factors for HP as compared to the control group of other IVF patients. The surgical treatment of HP does not appear to affect the rates of first trimester fetal loss or live birth. PMID:27366008

  20. A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation (VCA) Research

    PubMed Central

    Ibrahim, Zuhaib; Cooney, Damon S.; Shores, Jaimie T.; Sacks, Justin M.; Wimmers, Eric G.; Bonawitz, Steven C.; Gordon, Chad; Ruben, Dawn; Schneeberger, Stefan; Lee, W. P. Andrew; Brandacher, Gerald

    2013-01-01

    Vascularized Composite Allotransplantation (VCA) such as hand and face transplants represent a viable treatment option for complex musculoskeletal trauma and devastating tissue loss. Despite favorable and highly encouraging early and intermediate functional outcomes, rejection of the highly immunogenic skin component of a VCA and potential adverse effects of chronic multi-drug immunosuppression continue to hamper widespread clinical application of VCA. Therefore, research in this novel field needs to focus on translational studies related to unique immunologic features of VCA and to develop novel immunomodulatory strategies for immunomodulation and tolerance induction following VCA without the need for long term immunosuppression. This article describes a reliable and reproducible translational large animal model of VCA that is comprised of an osteomyocutaneous flap in a MHC-defined swine heterotopic hind limb allotransplantation. Briefly, a well-vascularized skin paddle is identified in the anteromedial thigh region using near infrared laser angiography. The underlying muscles, knee joint, distal femur, and proximal tibia are harvested on a femoral vascular pedicle. This allograft can be considered both a VCA and a vascularized bone marrow transplant with its unique immune privileged features. The graft is transplanted to a subcutaneous abdominal pocket in the recipient animal with a skin component exteriorized to the dorsolateral region for immune monitoring. Three surgical teams work simultaneously in a well-coordinated manner to reduce anesthesia and ischemia times, thereby improving efficiency of this model and reducing potential confounders in experimental protocols. This model serves as the groundwork for future therapeutic strategies aimed at reducing and potentially eliminating the need for chronic multi-drug immunosuppression in VCA. PMID:24145603

  1. 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

  2. PHAEOHYPHOMYCOSIS ASSOCIATED WITH OSSIFICATION OF THE SKULL AND CERVICAL VERTEBRAE IN A SWELL SHARK (CEPHALOSCYLLIUM VENTRIOSUM).

    PubMed

    Erlacher-Reid, Claire D; Nollens, Hendrik H; Schmitt, Todd L; St Leger, Judy; Sunico, Sarena

    2016-12-01

    A female, captive bred, juvenile swell shark ( Cephaloscyllium ventriosum ) was observed swimming in tight circles and rolling. Radiographs and computed tomography of this individual revealed extensive cartilage mineralization of the skull and cranial cervical vertebrae compared with diagnostic images of clinically healthy conspecifics. Gross necropsy and histopathologic examination revealed ossification and fibrosis of the cartilaginous matrix of the skull and cervical vertebrae with deep invasion by a pigmented hyphal fungus. There was no growth on fungal culture, but fungal polymerase chain reaction identified a DNA sequence compatible with Exophiala sp. (99%). Radiographs and computed tomography were helpful to determine a prognosis and course of action for this individual. This case emphasizes the need to include fungal infections as a differential diagnosis when evaluating elasmobranchs with abnormal swimming behaviors and mineralization of the skeletal structures.

  3. Fibrodysplasia ossificans progressiva in a Maine Coon cat with prominent ossification in dorsal muscle.

    PubMed

    Yabuzoe, Atsushi; Yokoi, Shin-ichi; Sekiguchi, Maiko; Momoi, Yasuyuki; Ide, Kaori; Nishifuji, Koji; Iwasaki, Toshiroh

    2009-12-01

    A one-year and six-month-old female Maine Coon cat presented with skin problems and paravertebral induration with a history of seven months. Survey radiographs and computed tomography revealed prominent calcifications in both sides of cervical, thoracic and lumbar vertebrae and soft tissue in femoral regions, below knee regions and in brachial regions. Histopathological findings from muscle biopsy samples showed connective tissue proliferation around adjacent skeletal muscle, cartilage formation and endochondral ossification. On the basis of these findings, this feline patient was diagnosed with fibrodysplasia ossificans progressiva (FOP). The most prominent signs observed in this FOP case were significant calcifications of dorsal muscle and presentation of cutaneous signs at the early stage.

  4. Avulsion fracture of the anterior inferior iliac spine with abundant reactive ossification in the soft tissue.

    PubMed

    Resnick, J M; Carrasco, C H; Edeiken, J; Yasko, A W; Ro, J Y; Ayala, A G

    1996-08-01

    Patients who have sustained an avulsion fracture and present clinically during the healing phase of the injury may manifest a mass that clinically and radiographically mimics a malignant neoplasm. A 15-year-old male soccer goalkeeper presented with a large ossified mass in the soft tissues overlying the right hip 6 months after experiencing a popping sensation in his hip joint during a game. Although an osteosarcoma was suspected clinically and radiographically, a Tru-Cut needle biopsy of the lesion revealed reactive bone formation. Correlation of the clinical, radiographic, and pathologic findings indicated an avulsion fracture of the anterior inferior iliac spine with abundant reactive ossification in the soft tissues. The healing phase of an avulsion fracture may clinically and radiographically be mistaken for neoplasia. In such cases, a Tru-Cut needle biopsy may reveal the reactive nature of the process.

  5. 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

  6. What understanding tendon cell differentiation can teach us about pathological tendon ossification.

    PubMed

    Magne, D; Bougault, C

    2015-08-01

    Tendons are the structures that attach muscles to bones and transmit mechanical forces. Tendon cells are composed of mature tenocytes and a rare population of tendon stem cells. Both cell types ensure homeostasis and repair of tendon extracellular matrix to guarantee its specific mechanical properties. Moreover, tendon cells seem to present a marked potential for trans-differentiation, predominantly into the chondrocyte and osteoblast lineages. In this review article, we first present chronic tendon pathologies associated with abnormal ossification, such as spondyloarthritis and calcifying tendinopathy, and discuss how tendon cell differentiation and trans-differentiation may participate in these diseases. We moreover present the factors known to influence tendon cell differentiation and trans-differentiation, with a particular emphasis on extracellular environment, mechanical stimulation and several soluble factors that can tip the balance toward one or another lineage. A better understanding of the neglected tendon cell biology may be extremely useful to understand the pathological mechanisms of spondyloarthritis and calcifying tendinopathy.

  7. 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.

  8. Cervical surgery for ossification of the posterior longitudinal ligament: One spine surgeon's perspective

    PubMed Central

    Epstein, Nancy E.

    2014-01-01

    Background: The selection, neurodiagnostic evaluation, and surgical management of patients with cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. Whether for prophylaxis or treatment, the decision to perform anterior vs. posterior vs. circumferential cervical OPLL surgery is complex. MR and CT Documentation of OPLL: Together, MR and CT cervical studies best document the full extent of OPLL. While MR provides the optimal soft-tissue overview (e.g. hyperintense signals reflecting edema/myelomalacia in the cord), CT's directly demonstrate the ossification of OPLL often “missed” by MR (e.g. documents the single or double layer signs of dural penetration. Patient Selection: Patients with mild myelopathy/cord compression rarely require surgery, while those with moderate/severe myelopathy/cord compression often warrant anterior, posterior, or circumferential approaches. Operative Approaches: Anterior corpectomies/fusions, warranted in patients with OPLL and kyphosis/loss of lordosis, also increase the risks of cerebrospinal fluid (CSF) leaks (e.g. single/double layer sign), and vascular injuries (e.g. carotid, vertebral). Alternatively, with an adequate lordosis, posterior procedures (e.g. often with fusions), may provide adequate multilevel decompression while minimizing risk of anterior surgery. Occasionally, combined pathologies may warrant circumferential approaches. Anesthetic and Intraoperative Monitoring Protocols: The utility of awake nasotracheal fiberoptic intubation/awake positioning, intraoperative somatosensory/motor evoked potential, and electromyographic monitoring, and the requirement for total intravenous anesthesia (TIVA) for OPLL surgery is also discussed. Conclusion: Anterior, posterior, or circumferential surgery may be warranted to treat patients with cervical OPLL, and must be based on careful patient selection, and both MR and CT documentation of the full extent of OPLL. PMID:24843818

  9. Dietary 135-fold cholecalciferol supplementation severely disturbs the endochondral ossification in growing dogs.

    PubMed

    Tryfonidou, M A; Holl, M S; Stevenhagen, J J; Buurman, C J; Deluca, H F; Oosterlaken-Dijksterhuis, M A; van den Brom, W E; van Leeuwen, J P T M; Hazewinkel, H A W

    2003-05-01

    The effects of excessive non-toxic dietary Vitamin D(3) supplementation on Ca homeostasis with specific effects on endochondral ossification and skeletal remodeling were investigated in a group of growing Great Dane dogs supplemented with cholecalciferol (Vitamin D(3); HVitD) versus a control group (CVitD) (1350 microg versus 11.4 microg Vitamin D(3) per kilogram diet) from 6 to 21 weeks of age. There were no differences between groups in plasma concentrations of total Ca, inorganic phosphate, growth hormone, and insulin-like growth factor I and no signs of Vitamin D(3) intoxication in HVitD. For the duration of the study in HVitD compared to CVitD, plasma levels of parathyroid hormone (PTH) decreased, calcitonin (CT) increased, 25-hydroxycholecalciferol [25(OH)D(3)] increased 30- to 75-fold, 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] increased 12- to 16-fold, and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] decreased by approximately 40%. The latter was attributed to the two-fold increased metabolic clearance rate in the HVitD versus CVitD accompanied by the absence of the anabolic effect of PTH on the production of 1,25(OH)(2)D(3). Fractional Ca absorption (alpha) did not differ between groups at 8 and 14 weeks of age, whereas at 20 weeks of age alpha increased by only 16.4% in HVitD compared to CVitD. Excessive non-toxic Vitamin D(3) supplementation resulted in decreased bone remodeling and focal enlargement of the growth plate with morphology resembling those induced by administration of CT. Hypercalcitoninemia and the imbalanced relationship between 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3) are potent candidates for the disturbed endochondral ossification.

  10. Preservation of left ventricular function and morphology in volume-loaded versus volume-unloaded heterotopic heart transplants.

    PubMed

    Didié, Michael; Biermann, Daniel; Buchert, Ralph; Hess, Andreas; Wittköpper, Katrin; Christalla, Peter; Döker, Stephan; Jebran, Fawad; Schöndube, Friedrich; Reichenspurner, Hermann; El-Armouche, Ali; Zimmermann, Wolfram-Hubertus

    2013-08-15

    Total mechanical unloading of the heart in classical models of heterotopic heart transplantation leads to cardiac atrophy and functional deterioration. In contrast, partial unloading of failing human hearts with left ventricular (LV) assist devices (LVADs) can in some patients ameliorate heart failure symptoms. Here we tested in heterotopic rat heart transplant models whether partial volume-loading (VL; anastomoses: aorta of donor to aorta of recipient, pulmonary artery of donor to left atrium of donor, superior vena cava of donor to inferior vena cava of recipient; n = 27) is superior to the classical model of myocardial unloading (UL; anastomoses: aorta of donor to aorta of recipient, pulmonary artery of donor to inferior vena cava of recipient; n = 14) with respect to preservation of ventricular morphology and function. Echocardiography, magnetic resonance imaging, and LV-pressure-volume catheter revealed attenuated myocardial atrophy with ~30% higher LV weight and better systolic contractile function in VL compared with UL (fractional area shortening, 34% vs. 18%; maximal change in pressure over time, 2,986 ± 252 vs. 2,032 ± 193 mmHg/s). Interestingly, no differences in fibrosis (Picrosirus red staining) or glucose metabolism (2-[18F]-fluoro-2-deoxy-D-glucose-PET) between VL and UL were observed. We conclude that the rat model of partial VL attenuates atrophic remodelling and shows superior morphological as well as functional preservation, and thus should be considered more widely as a research model.

  11. Ruptured heterotopic pregnancy in a natural conception cycle: a case report at the Yaounde central Hospital (Cameroon)

    PubMed Central

    Fouedjio, Jeanne Hortence; Fouelifack, Florent Ymele; Fouogue, Jovanny Tsuala; Sando, Zacharie

    2013-01-01

    Heterotopic pregnancy is very rare under natural circumstances. We report the case of a 28 year old Gravida2 Para1001 woman at 9 weeks of pregnancy who consulted in emergency for acute pelvic pain following metrorrhagia. Physical exam revealed hemoperitoneum without shock. An emergency ultrasonography revealed two gestational sacs, one intra-uterine and the other extra-uterine. Laparotomy was done and the findings were: a ruptured right tubal pregnancy with 1,300 milliliters of hemoperitoneum, type B left utero-adnexal adhesions and an increased uterus consistent with a 9 weeks pregnancy. Right total salpingectomy was done and the patient did well postoperatively. That intrauterine pregnancy evolved normally under progesterone supply and the woman delivered a termed live female baby weighing 3.1 kilogrammes. In our context where ultrasound is not always available, practitioners carrying out salpingectomy for ruptured ectopic pregnancies should bear in mind the plausibleness of heterotopic pregnancy in order to properly handle the uterus. PMID:24876895

  12. ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice

    PubMed Central

    Guaiquil, Victor H.; Swendeman, Steven; Zhou, Wenhui; Guaiquil, Patricio; Weskamp, Gisela; Bartsch, Jörg W.

    2010-01-01

    ADAM8 is a member of the “a disintegrin and metalloproteinase” (ADAM) family of membrane-anchored metalloproteinases. ADAM8-deficient mice have no evident spontaneous developmental or pathological defects, and little is currently known about the role of ADAM8 in disease. Here, we investigated the contribution of ADAM8 to pathological neovascularization in mice using an oxygen-induced retinopathy (OIR) model and heterotopical injection of tumor cells. We found an increase in retinal re-vascularization but fewer neovascular tufts in the OIR model and increased growth of heterotopically injected tumor cells in Adam8−/− mice compared with wild-type controls. These results suggest that ADAM8 functions to limit both of these processes in wild-type mice. In cell-based assays, overexpression of ADAM8 increased the ectodomain shedding of several co-expressed membrane proteins with roles in angiogenesis (CD31, Tie-2, Flk-1, Flt-1, EphrinB2, EphB4, VE-cadherin, KL-1, E-selectin, and neuregulin-1β2). Thus, dysregulated expression of ADAM8 in endothelial cells in vivo could potentially increase the processing of these and other substrate proteins. Taken together, our findings suggest that inhibiting ADAM8 could be useful for promoting re-vascularization and thereby preventing formation of neovascular tufts in proliferative retinopathies. On the other hand, blocking ADAM8 could be detrimental in the context of rapidly growing tumors. PMID:20119708

  13. Evolution of ossification sequences in salamanders and urodele origins assessed through event-pairing and new methods.

    PubMed

    Germain, Damien; Laurin, Michel

    2009-01-01

    Ossification sequences of the skull in extant Urodela and in Permo-Carboniferous Branchiosauridae have already been used to study the origin of lissamphibians. But most of these studies did not consider some recent methods developed to analyze the developmental sequences within a phylogenetic framework. Here, we analyze the ossification sequences of 24 cranial bones of 23 extant species of salamanders using the event-pairing method. This reveals new developmental synapomorphies for several extant salamander taxa and ancestral sequences for Urodela under four alternative reference phylogenies. An analysis with the 12 bones for which ossification sequence data are available in urodeles and in the branchiosaurid Apateon is also performed in order to compare the ancestral condition of the crown-group of Urodela to the sequence of Apateon. This reveals far more incompatibilities than previously suggested. The similarities observed between some extant salamanders and branchiosaurids may result from extensive homoplasy, as the extreme variation observed in extant Urodela suggests, or be plesiomorphic, as the conservation of some ossification patterns observed in other remotely related vertebrates like actinopterygians suggests. We propose a new, simpler method based on squared-change optimization to estimate the relative timing of ossification of various bones of hypothetical ancestors, and use independent-contrasts analysis to estimate the confidence intervals around these times. Our results show that the uncertainty of the ancestral ossification sequence of Urodela is much greater than event-pairing suggests. The developmental data do not allow to conclude that branchiosaurids are closely related to salamanders and their limited taxonomic distribution in Paleozoic taxa precludes testing hypotheses about lissamphibian origins. This is true regardless of the analytical method used (event-pairing or our new method based on squared-change parsimony). Simulations show that

  14. An unusual form of spondyloepiphyseal dysplasia, with advanced carpal and spinal end-plate ossification mimicking COMP-mutation-like multiple epiphyseal dysplasia.

    PubMed

    Pazzaglia, Ugo Ernesto; Beluffi, Giampiero; Zarattini, Guido

    2008-07-01

    We present a child with irregular ossification of tubular bone epiphyses, short bones, and spine. The radiographic evolution of bones undergoing endochondral ossification was followed from the age of 1 year 9 months to 6 years. The unusual features demonstrated in this child made classification difficult: pseudoachondroplasia was excluded because no mutations of the COMP gene were found. Considering the evolution of the radiographic appearances, the most likely diagnosis would seem to be an unusual form of spondyloepiphyseal dysplasia, mimicking some aspects of multiple epiphyseal dysplasia. Endochondral ossification was diffusely altered with a mixture of epiphyseal ossification delay associated with acceleration and early fusion. This case was a unique presentation within the family, suggesting a mutation in the affected child.

  15. Visualization of Ca2+-Induced Phospholipid Domains

    NASA Astrophysics Data System (ADS)

    Haverstick, Doris M.; Glaser, Michael

    1987-07-01

    Large vesicles (5-15 μ m) were formed by hydrating a dried lipid film containing phospholipids labeled with a fluorophore in one fatty acid chain. By using a fluorescence microscope attached to a low-light-intensity charge-coupled-device camera and digital-image processor, the vesicles were easily viewed and initially showed uniform fluorescence intensity across the surface. The fluorescence pattern of vesicles made with a fluorophore attached to phosphatidylcholine or phosphatidylethanolamine was unaffected by the presence of divalent cations such as Ca2+, Mg2+, Mn2+, Zn2+, or Cd2+. The fluorescence pattern of vesicles containing a fluorophore attached to the acidic phospholipids phosphatidylserine or phosphatidic acid showed distinct differences when treated with Ca2+ or Cd2+, although they were unaffected by Mg2+, Mn2+, or Zn2+. Treatment with 2.0 mM Ca2+ or Cd2+ resulted in the movement of the fluorophore to a single large patch on the surface of the vesicle. When vesicles were formed in the presence of 33 mol% cholesterol, patching was seen at a slightly lower Ca2+ concentration (1.0 mM). The possibility of interactions between Ca2+ and acidic phospholipids in plasma membranes was investigated by labeling erythrocytes and erythrocyte ghosts with fluorescent phosphatidic acid. When Ca2+ was added, multiple (five or six) small patches were seen per individual cell. The same pattern was observed when vesicles formed from whole lipid extracts of erythrocytes were labeled with fluorescent phosphatidic acid and then treated with Ca2+. This shows that the size and distribution of the Ca2+-induced domains depend on phospholipid composition.

  16. 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

  17. Heterotopic Pregnancy After In Vitro Fertilization and Embryo Transfer After Bilateral Total Salpingectomy/Tubal Ligation: Case Report and Literature Review.

    PubMed

    Xu, Ying; Lu, Yingli; Chen, Huiling; Li, Dandan; Zhang, Jingwen; Zheng, Lianwen

    2016-01-01

    Heterotopic pregnancy is defined as the simultaneous occurrence of intrauterine and ectopic pregnancy, either of which may be single or multiple. It occurs in up to 1% of pregnancies after in vitro fertilization and embryo transfer. This article reports 2 rare cases of heterotopic pregnancy after in vitro fertilization and presents a literature review. In the first case, a 28-year-old woman had previous laparoscopic bilateral total salpingectomy for a right tubal pregnancy and a left hydrosalpinx. However, she had ovarian heterotopic pregnancy after a third in vitro fertilization cycle. Emergency laparotomy was performed. The synchronous intrauterine pregnancy continued with no further complications and ended in the delivery of a singleton term pregnancy. The second case combined interstitial and intrauterine pregnancies after bilateral tubal ligation for hydrosalpinges followed by in vitro fertilization and frozen embryo transfer. The possibility of heterotopic pregnancy after bilateral total salpingectomy/tubal ligation, although extremely rare, should also be considered by gynecologists when they treat an in vitro fertilization patient even though an intrauterine pregnancy has been confirmed.

  18. Morphology and function of cryopreserved whole ovine ovaries after heterotopic autotransplantation

    PubMed Central

    Grazul-Bilska, Anna T; Banerjee, Jashoman; Yazici, Ilker; Borowczyk, Ewa; Bilski, Jerzy J; Sharma, Rakesh K; Siemionov, Maria; Falcone, Tommaso

    2008-01-01

    . Proliferating cells were detected in follicles, and the rate of apoptosis was minimal in ovaries of control and autotransplanted ovaries. Conclusion These data demonstrate successful autotransplantation of a portion of frozen/thawed ovaries manifested by restoration of selected ovarian function including in vitro maturation of collected oocytes, presence of follicles from several stages of folliculogenesis and blood vessels expressing specific markers of vascularization, and proliferation and apoptosis of ovarian cells. Thus, heterotopic autotransplantation of a whole frozen/thawed ovary allows for development of preovulatory follicles, oocyte growth, and for restoration of vascularization and cellular function. However, additional improvements are required to enhance the efficiency of autotransplantation of frozen/thawed ovaries to produce more oocytes. PMID:18402709

  19. 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

  20. Mono- and dimeric complexes of an asymmetric heterotopic P,CNHC,pyr ligand.

    PubMed

    Bouché, Mathilde; Mordan, Michael; Kariuki, Benson M; Coles, Simon J; Christensen, Jeppe; Newman, Paul D

    2016-09-14

    An asymmetric heterotopic ligand (S-N(Me)CP) containing a central bicyclic, expanded-ring NHC with one pyridyl and one phosphine exo-substituent has been synthesised and its coordination chemistry with selected late transition metals investigated. The amidinium precursor [S-N(Me)CHP]PF6 shows variable coordination modes with Ag(i), Cu(i) and Au(i) depending on the L : M ratio. The reaction of two mols of [S-N(Me)CHP]PF6 with [Cu(MeCN)4]BF4, AgBF4 or Au(THT)Cl gives the bis-ligand complexes [Cu(κ-P-N(Me)CHP)2(CH3CN)2]BF4·(PF6)2, 1, and [M(κ-P-N(Me)CHP)2]X·(PF6)2 (3: M = Ag, X = BF4; 6: M = Au, X = Cl) respectively. The 1 : 1 reaction of [S-N(Me)CHP]PF6 with AgOTf gave the head-to-tail dimer H,T-[Ag2(μ-N,P-N(Me)CHP)2(μ-OTf)2](PF6)2, 2, whereas the analogous reaction with Au(THT)Cl gave monomeric [Au(κ-P-N(Me)CHP)Cl]PF6, 5. Complex 2 was converted to H,T-[Ag2(μ-C,P-N(Me)CP)2](PF6)2, 4, upon addition of base, while 6 gave [Au(κ-C-N(Me)CP)2]Cl, 8, when treated likewise. Reaction of [S-N(Me)CHP]PF6 with Ni(1,5-COD)2 gave the oxidative addition/insertion product [Ni(κ(3)-N,C,P-N(Me)CP)(η(3)-C8H13)]PF6, 9, which converted to [Ni(κ(3)-N,C,P-N(Me)CP)Cl]PF6, 10, upon exposure of a CHCl3 solution to air. Complex 10 showed conformational isomerism that was also present in [Rh(κ(3)-N,C,P-N(Me)CP)(CO)]PF6, 14, prepared from the precursor complex [Rh(κ-P-N(Me)CHP)(acac)(CO)]PF6, 13, upon heating in C6H5Cl. [Pt(κ(3)-N,C,P-N(Me)CP)(Cl)]PF6, 12, derived from trans-[Pt(κ-P-N(Me)CHP)2(Cl)2](PF6)2, 11, was isolated as a single conformer.

  1. Comparison of Acute Rejection in Sensitized (“Domino”) and Unsensitized Donor Hearts following Heterotopic Transplantation

    PubMed Central

    Schuetz, Albert; Breuer, Martin; Engelhardt, Michael; Brandl, Ulrike; Hammer, Claus; Kemkes, Bernhard M.

    1991-01-01

    scintigraphy, accurately revealed the various stages of acute rejection in all groups (p < 0.001). We conclude that the native heart appears to become sensitized during acute rejection episodes of a heterotopically transplanted heart. Cytoimmunologic monitoring and calculation of T-cell/B-cell ratios support this conclusion. In addition, we conclude that cyto-immunologic monitoring and antimyosin scintigraphy are highly specific and sensitive tools for diagnosis of cellular rejection. (Texas Heart Institute Journal 1991;18:286-92) PMID:15227412

  2. Sex-difference in the ossification rate of the appendicular skeleton in Capra pyrenaica Schinz, 1838, and its utility in the sex identification of long bones.

    PubMed

    Serrano, E; Pérez, J M; Christiansen, P; Gállego, L

    2006-04-01

    The main goal of our work is to quantify differences in the rate of ossification in post-cranial Iberian ibex skeletons, related to sex. Another objective is to improve criteria for assessing the sex of post-cranial bones by combining the degree of ossification of the distal epiphysis and biometrical data. Forty Capra pyrenaica skeletons were examined in order to determine the degree of ossification by means of an Ossification Index. Our results evidence that sexual differences in the rate of ossification become visible at 6 months of age. On average, females complete their bone development 2 years before males do. Finally, by means of lineal classification functions which take into account both biometrical and anatomical criteria, we can achieve, in average, a 95.5% of correct sex discrimination within a sample consisting of ibex metacarpi and metatarsi from individuals aging from <1 to 12 years. Therefore, we conclude that the rhythm of ossification in the post-cranial skeleton of C. pyrenaica may be used as a criterion for assessing the sex of skeletal remains and could be applicable to other dimorphic ungulates. Nevertheless, the results obtained for specimens belonging to a particular population may have limited application to other populations with different medium sizes and living at particular densities within habitats with variable quality.

  3. Ossification post-traumatique du ligament collatéral médial du genou: à propos d’un cas

    PubMed Central

    Arabi, Hafid; Sellahi, Hicham

    2016-01-01

    L’ossification hétérotopique est une ossification pathologique des parties molles. C’est une affection bénigne, récidivante et de survenue imprévisible. On décrit le cas d’un patient, traité pour une fracture du plateau tibial gauche avec mise en place d’une plaque vissée. A deux mois de l’opération, le patient a présenté une raideur du genou gauche. Le bilan radiologique standard a révélé une ossification du ligament latéral interne (LLI), confirmée par la tomodensitométrie. On ne sait pas actuellement les facteurs déterminant l’ossification des ligaments et tendons. Bien que les cliniciens prescrivent souvent des médicaments prophylactiques tels que les anti-inflammatoires et des séances de radiothérapie pour prévenir l’ossification hétérotopique des parties molles; la physiopathologie de l’ossification hétérotopique est peu connue. PMID:27800107

  4. Segmental Subtotal Corpectomy and Reconstruction With Titanium Cage and Anterior Plate for Multilevel Ossification of the Posterior Longitudinal Ligament.

    PubMed

    Zhang, Tao; Guo, Ying; Hu, Naiwu; Chen, Limin; Wu, Yin; Wang, Yang; Liu, Libing; Zhao, Chengbin

    2016-11-01

    This retrospective study assessed the outcomes of segmental subtotal corpectomy with titanium cage reconstruction and anterior plate fixation for multilevel ossification of the posterior longitudinal ligament. The study included 34 patients with multilevel ossification of the posterior longitudinal ligament who underwent segmental subtotal corpectomy with titanium cage reconstruction and anterior plate fixation from June 2005 to May 2011. Clinical and radiologic data were obtained. Neurologic function was evaluated by Japanese Orthopedic Association scores before and after surgery. No death, paralysis, or other surgically associated injuries occurred. After surgery, the bone graft fusion was firm, with no cases of lack of postoperative bone fusion, broken or loose titanium plate and screws, dislodged titanium cage, or injury to the vertebral artery, nerve root, or spinal cord. Cerebrospinal fluid leakage occurred in 2 cases. Japanese Orthopedic Association scores improved from 6.74±1.82 preoperatively to 11.33±3.5 postoperatively (P<.05). Neurologic outcomes were excellent or good in 84.21% of patients at follow-up of 1 to 6 years. No postoperative cerebrospinal fluid leakage occurred. Reasonable and skilled operation of the pneumatic drill is the key to successful surgery. Anterior corpectomy with titanium cage reconstruction and plate fixation and drilling applications can directly remove the hypertrophy and ossification of the posterior longitudinal ligament and relieve spinal cord compression. This technique retained the integrity of the vertebrae, increasing the possibility of bone graft healing. Segmental subtotal corpectomy with titanium cage reconstruction and anterior plate fixation can be used for the treatment of multilevel ossification of the posterior longitudinal ligament. [Orthopedics. 2016; 39(6):e1140-e1146.].

  5. Static osteogenesis does not precede dynamic osteogenesis in periosteal ossification of Pleurodeles (Caudata, Amphibia) and Pogona (Squamata, Lepidosauria).

    PubMed

    Cubo, Jorge; Hui, Mylaine; Clarac, François; Quilhac, Alexandra

    2017-02-01

    Two successive mechanisms have been described in perichondral ossification: (1) in static osteogenesis, mesenchymal cells differentiate into stationary osteoblasts oriented randomly, which differentiate into osteocytes in the same site; (2) in dynamic osteogenesis, mesenchymal cells differentiate into osteoblasts that are all oriented in the same direction and move back as they secrete collagen fibers. This study is aimed at testing the hypothesis that the ontogenetic sequence static then dynamic osteogenesis observed in the chicken and in the rabbit is homologous and was acquired by the last common ancestor of amniotes or at a more inclusive node. For this we analyze the developmental patterns of Pleurodeles (Caudata, Amphibia) and those of the lizard Pogona (Squamata, Lepidosauria). We processed Pleurodeles larvae and Pogona embryos, prepared thin and ultrathin sections of appendicular bones, and analyzed them using light and transmission electron microscopy. We show that static osteogenesis does not precede dynamic osteogenesis in periosteal ossification of Pleurodeles and Pogona. Therefore, the null hypothesis is rejected and according to the parsimony method the ontogenetic sequence observed in the chicken and in the rabbit are convergent. In Pleurodeles and Pogona dynamic osteogenesis occur without a previous rigid mineralized framework, whereas in the chicken and in the rabbit dynamic osteogenesis seems to take place over a mineralized support whether bone (in perichondral ossification) or calcified cartilage (in endochondral ossification). Interestingly, in typical dynamic osteogenesis, osteoblasts show an axis (basal nucleus-distal endoplasmic reticulum) perpendicular to the front of secreted unmineralized bone matrix, whereas in Pleurodeles and Pogona this axis is parallel to the bone matrix.

  6. Metaplastic ossification of the temporal artery with osteoclast-like giant cells: a mimicker of giant cell (temporal) arteritis.

    PubMed

    Sekulic, Miroslav; Truskinovsky, Alexander M

    2017-05-11

    To describe a patient presenting with suspected giant cell (temporal) arteritis (GCA) in whom subsequent temporal artery biopsy showed luminal narrowing by medial calcification, metaplastic ossification, and fibrointimal proliferation, consistent with calciphylaxis. A 55-year-old man with end-stage renal disease presented with unilateral loss of vision and elevated erythrocyte sedimentation rate and was initially treated as though he had GCA; however, a subsequent temporal artery biopsy showed marked luminal narrowing by medial calcification, metaplastic ossification, and fibrointimal proliferation, consistent with calciphylaxis. In addition, the tunica media of the affected artery contained multinucleate giant cells, but these represented osteoclasts and foreign body giant cells reacting to calcium, rather than a part of GCA. This is a rare report of metaplastic ossification and the finding of non-GCA-related giant cells in the tunica media of the temporal artery, thus representing a clinical and histopathologic mimicker of GCA. The clinical differential diagnosis of GCA includes other etiologies that can present similarly; however, temporal artery biopsy can discern the underlying pathology. Importantly, the identification of giant cells is not required for the diagnosis of GCA, and likewise, as our case shows, the finding of giant cells in the wall of a temporal artery does not always imply a diagnosis of GCA.

  7. 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.

  8. Lateral Lumbar Interbody Fusion for Ossification of the Yellow Ligament in the Lumbar Spine: First Reported Case

    PubMed Central

    Abe, Tetsuya; Funayama, Toru; Noguchi, Hiroshi; Nakayama, Keita; Miura, Kousei; Nagashima, Katsuya; Kumagai, Hiroshi; Yamazaki, Masashi

    2017-01-01

    When ossification of the yellow ligament (OYL) occurs in the lumbar spine and extends to the lateral wall of the spinal canal, facetectomy is required to remove all of the ossified lesion and achieve decompression. Subsequent posterior fixation with interbody fusion will then be necessary to prevent postoperative progression of the ossification and intervertebral instability. The technique of lateral lumbar interbody fusion (LLIF) has recently been introduced. Using this procedure, surgeons can avoid excess blood loss from the extradural venous plexus and detachment of the ossified lesion and the ventral dura mater is avoidable. We present a 55-year-old male patient with OYL at L3/4 and anterior spondylolisthesis of L4 vertebra, with concomitant ossification of the posterior longitudinal ligament, who presented with a severe gait disturbance. He underwent a 2-stage operation without complications: LLIF for L3/4 and L4/5 was performed at the initial surgery, and posterior decompression fixation using pedicle screws from L3 to L5 was performed at the second surgery. His postoperative progress was favorable, and his interbody fusion was deemed successful. Here, we present the first reported case of LLIF for OYL of the lumbar spine. This procedure can be a good option for OYL of the lumbar spine. PMID:28352485

  9. Immature muscular tissue differentiation into bone-like tissue by bone morphogenetic proteins in vitro, with ossification potential in vivo.

    PubMed

    Hayashi, Tatsuhide; Kobayashi, Syuichiro; Asakura, Masaki; Kawase, Mayu; Ueno, Atsuko; Uematsu, Yasuaki; Kawai, Tatsushi

    2014-09-01

    The objective of this study was to induce bone formation from immature muscular tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition, cultured IMTs were implanted subcutaneously into Sprague-Dawley (SD) rats to determine their in vivo ossification potential. BMPs, extracted from bovine cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks culture on ePTFE scaffolds. Osteoblast-like cells and osteoid tissues were partially identified by hematoxylin-eosin staining 2 weeks after culture. Collagen type I (Col-I), osteopontin (OP), and osteocalcin (OC) were detected in the osteoid tissues by immunohistochemical staining. OC gene expression remained low, but OP and Col-I were upregulated during the culture period. In vivo implanted IMTs showed slight radiopacity 1 week after implantation and strong radiopacity 2 and 3 weeks after implantation. One week after implantation, migration of numerous capillaries was observed and ossification was detected after 2 weeks by histological observation. These results suggest that IMTs are able to differentiate into bone-like tissue in vitro, with an ossification potential after implantation in vivo.

  10. Formation and ossification of limb elements in Trachemys scripta and a discussion of autopodial elements in turtles.

    PubMed

    Sheil, Christopher A; Portik, Daniel

    2008-06-01

    Though sequences of formation and ossification of bony elements have been described for many taxa, controversy surrounds the formation of limb elements in turtles. Three hypotheses for patterns of formation of autopodial elements have been proposed, differing primarily in the origin of Distal Carpal/Tarsal 3, the digital arch, and Centrale 4. Patterns of formation and ossification of limb elements are described for Trachemys scripta. These patterns are compared to similar data for representatives of four families of turtles (Cheloniidae, Chelydridae, Emydidae, and Trionychidae). Hypotheses of limb formation are compared in the context of new and published data. Three species (Trachemys scripta, Chrysemys picta, and Chelydra serpentina) suggest that Distal Carpal 3 forms by branching from the ulnare, whereas Distal Carpal 3 may branch from Distal Carpal 4 in Macrochelys temminckii and Chelonia mydas; data from Graptemys nigrinoda, Apalone spinifera, and Eretmochelys imbricata did not provide evidence for the origin of Distal Carpal 3. Centrale 4 was not observed to branch from the ulnare and apparently arises by de-novo condensation. Distal Carpal 4 did not branch from Centrale 4 in any species. Until the developmental origins of Distal Carpal 3 and Centrale 4 are understood, interspecific variation in the origin of these elements remains, and may explain some of the observed differences. Trends of ossification in the fore- and hind limb autopodium also are summarized. Homology of elements in pedal Digit V is discussed, and we suggest that the hooked proximal element of this digit be recognized as Distal Tarsal 5.

  11. 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.

  12. Cervical vertebral injuries associated with the ossification of the posterior longitudinal ligament: Imaging features

    PubMed Central

    Ehara, Shigeru

    2017-01-01

    Background Spinal injuries associated with ossification of the posterior longitudinal ligament (OPLL) have been characterized. However, the imaging features of traumatic cervical spine fractures in patients with OPLL have not been assessed adequately. Purpose To characterize the patterns of traumatic cervical spine fractures associated with different types of OPLL. Material and Methods We retrospectively analyzed the patterns of fractures resulting from cervical spine injury in patients with OPLL of different types and assessed the fracture patterns in patients with ankylosed segments. Results Twenty-six patients (23 men, 3 women; median age, 67.0 years; age range, 43–87 years) were included. Fall from a height <3 m was the most common trauma. Contiguous type OPLL was seen in 11 patients (42%), segmental type in 11 (42%), and mixed type in four (15%). Four of the contiguous OPLL and one of the mixed OPLL patients had ankylosed segments. The incidence of cervical fractures was 69% (16/26): seven (64%) in contiguous OPLL, five (46%) in segmental OPLL, and in all four patients with mixed OPLL. Unilateral interfacetal fracture-dislocation was most common (4/16); the others were bilateral interfacetal fracture-dislocation, fractures through the ankylosed segment, transdiscal fractures, isolated facet fractures, and compression fractures. Cervical fractures were exclusively observed in the C4 to C7, except in one case occurred at the C2 level. Conclusion Interfacetal fracture-dislocation in the lower cervical vertebrae constitutes the most common injury resulting from minor trauma. PMID:28321332

  13. Investigation of aluminum and iron deposition on metaplastic bones in three patients with diffuse pulmonary ossification.

    PubMed

    Ohtsuki, Yuji; Mori, Kousuke; Ohnishi, Hirozo; Enzan, Hideaki; Iguchi, Mitsuko; Lee, Gang-Hong; Furihata, Mutsuo

    2015-12-01

    Diffuse pulmonary ossification (DPO) is a rare pulmonary lesion. DPO is typically detected at autopsy rather than premortem. Recently, however, several cases were diagnosed antemortem using computed tomography, high-resolution computed tomography, or video-assisted thoracic surgery. In the present study, we evaluated DPO at autopsy from two patients with post-myocardial infarction (cases 1 and 3) and one patient with duodenal cancer (case 2). Multiple metaplastic bones (nodular in case 1 and 3 or dendriform in case 2) were detected in these three cases. In an attempt to detect aluminum and iron deposition in these metaplastic bones, histochemical investigations were performed. The two nodular types of one and three cases were positive for aluminum and iron, but the dendriform type of case 2 was positive only for aluminum. The depositions occurred in a linear pattern along the calcifying front. It is of great interest that these deposition patterns were similar to those of bones from three previously reported DPO cases and from the bones of hemodialysis patients. It is suggested that these abnormal metal depositions in the calcifying front might disturb the normal mineralization processes of the metaplastic bones, although no morphological abnormality was detected, except for dense black color of calcifying front lines. Further investigations are needed in more patients with DPO to obtain more information on this topic.

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

    SciTech Connect

    Tsuji, Takehito Kondo, Eri; Yasoda, Akihiro; Inamoto, Masataka; Kiyosu, Chiyo; Nakao, Kazuwa; Kunieda, Tetsuo

    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 induce 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.

  15. Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice.

    PubMed

    Liu, Kang; Wu, Lianguo; Shi, Xiaolin; Wu, Fengqing

    2016-08-01

    Naringin is an abundant flavanone in pomelo, grapefruit as well as lime and its variants, has been shown to exhibit certain antioxidative, anti-inflammatory, anti-cancer and hypoglycemic effects. The aim of the current study was to evaluate the protective effects of naringin against ankylosing spondylitis (AS) and to elucidate the potential underlying mechanism. Firstly, a mouse model of ankylosing spondylitis (AS) was established. Next, osteocalcin (OC), alkaline phosphatase (ALP) and triglyceride (TG) activity values, inflammatory factor and oxidative stress were evaluated in the AS mice. Then, the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) protein expression levels in the AS mice were investigated using western blot analysis. The results showed that naringin increased OC, ALP and TG activity values in the AS mouse model. Furthermore, inflammatory factor and oxidative stress levels in the AS mice were restrained by treatment with naringin. Furthermore, JAK2 and STAT3 protein expression levels were reduced by treatment with naringin. In conclusion, the present results indicated that the protective effects of naringin against AS are exerted via the induction of ossification, suppression of inflammation and oxidative stress and the downregulation of JAK2/STAT3 in mice.

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

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26309799

  17. Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice

    PubMed Central

    Liu, Kang; Wu, Lianguo; Shi, Xiaolin; Wu, Fengqing

    2016-01-01

    Naringin is an abundant flavanone in pomelo, grapefruit as well as lime and its variants, has been shown to exhibit certain antioxidative, anti-inflammatory, anti-cancer and hypoglycemic effects. The aim of the current study was to evaluate the protective effects of naringin against ankylosing spondylitis (AS) and to elucidate the potential underlying mechanism. Firstly, a mouse model of ankylosing spondylitis (AS) was established. Next, osteocalcin (OC), alkaline phosphatase (ALP) and triglyceride (TG) activity values, inflammatory factor and oxidative stress were evaluated in the AS mice. Then, the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) protein expression levels in the AS mice were investigated using western blot analysis. The results showed that naringin increased OC, ALP and TG activity values in the AS mouse model. Furthermore, inflammatory factor and oxidative stress levels in the AS mice were restrained by treatment with naringin. Furthermore, JAK2 and STAT3 protein expression levels were reduced by treatment with naringin. In conclusion, the present results indicated that the protective effects of naringin against AS are exerted via the induction of ossification, suppression of inflammation and oxidative stress and the downregulation of JAK2/STAT3 in mice. PMID:27446336

  18. Interaction of zinc with cadmium and copper on ossification of embryonic chick bone in tissue culture.

    PubMed

    Kaji, T; Takata, M; Miyahara, T; Kozuka, H; Koizumi, F

    1990-01-01

    Histological changes are shown of ossification induced by a simultaneous exposure to zinc and cadmium or to zinc and copper using embryonic chick femur in a culture system. Cadmium caused an atrophic change of the osseous tissue in the absence of zinc but caused an osteomalacic change with a partial degenerative change in the presence of zinc after a 6-day culture. Copper caused an atrophic change in the absence or presence of zinc. These observations were partly supported by the fact that the diaphysial calcium content was significantly decreased by zinc alone, and the decrease was unaffected by cadmium or copper. Zinc significantly decreased cadmium accumulation but not copper accumulation in the diaphysis. Thus, in spite of the inhibitory effect on calcification, zinc prevented a decrease in bone matrix formation caused by cadmium but not that by copper. Exposure of chick femur culture to zinc and cadmium induced changes consistent with osteomalacia, i.e., decreased mineralization of bone, with or without suppression of matrix formation. Exposure to zinc and copper, however, induced changes consistent with osteoporosis, i.e., decreased mineralization and matrix formation.

  19. Monocytes Seeded on Engineered Hypertrophic Cartilage Do Not Enhance Endochondral Ossification Capacity.

    PubMed

    Todorov, Atanas; Scotti, Celeste; Barbero, Andrea; Scherberich, Arnaud; Papadimitropoulos, Adam; Martin, Ivan

    2017-07-01

    Engineered hypertrophic cartilage (HC) represents an attractive bone substitute material, capable to induce bone formation by endochondral ossification. Since bone formation by HC depends on factors released from the extracellular matrix, in this study, we hypothesized that HC seeding with monocytes committed to osteoclastogenesis could enhance its remodeling, improve chemotaxis of skeletal and vascular cells, and consequently enhance bone formation. This would be particularly relevant for devitalized HC, which currently exhibits only limited osteoinductivity. Living or devitalized HC engineered from human bone marrow-derived mesenchymal stromal cells (MSCs) was seeded or not with human monocytes in the presence of macrophage colony-stimulating factor and RANK-ligand, cultured for up to 15 days, or implanted ectopically in nude mice. Monocytes seeded on devitalized, but not living, HC induced its in vitro resorption, resulting in 30-fold higher release and 2.7-fold lower content of glycosaminoglycans compared with unseeded samples. In vitro, supernatants from monocyte-seeded devitalized HC attracted more monocytes compared with unseeded samples, but did not enhance chemotaxis of MSCs or human umbilical vein endothelial cells. In vivo, however, neither remodeling nor invasion by osteoclasts, endothelial cells, and mouse MSCs were significantly affected by the seeding with monocytes. Finally, in vitro priming of living or devitalized HC by monocytes did not enhance their bone-forming capacity. Further investigations should test the proposed approach on HC engineered to prevent rapid degradation and support osteoclastogenesis, or identify alternative strategies to enhance engineered HC remodeling and bone-forming capacity.

  20. Spontaneous Cervical Intradural Disc Herniation Associated with Ossification of Posterior Longitudinal Ligament

    PubMed Central

    Wang, Dachuan; Wang, Haifeng; Shen, Wun-Jer

    2014-01-01

    Intradural herniation of a cervical disc is rare; less than 35 cases have been reported to date. A 52-year-old man with preexisting ossification of posterior longitudinal ligament developed severe neck pain with Lt hemiparesis while asleep. Neurological exam was consistent with Brown-Séquard syndrome. Magnetic resonance images showed a C5-6 herniated disc that was adjacent to the ossified ligament and indenting the cord. The mass was surrounded by cerebrospinal fluid signal intensity margin, and caudally the ventral dura line appears divided into two, consistent with the “Y-sign” described by Sasaji et al. Cord edema were noted. Because of preexisting canal stenosis and spinal cord at risk, a laminoplasty was performed, followed by an anterior C6 corpectomy. Spot-weld type adhesions of the posterior longitudinal ligament to the dura was noted, along with a longitudinal tear in the dura. An intradural extra-arachnoid fragment of herniated disc was removed. Clinical exam at 6 months after surgery revealed normal muscle strength but persistent mild paresthesias. It is difficult to make a definite diagnosis of intradural herniation preoperatively; however, the clinical findings and radiographic signs mentioned above are suggestive and should alert the surgeon to look for an intradural fragment. PMID:25295205

  1. Investigation of ossification in the posterior longitudinal ligament using micro-focus X-ray CT scanning and histological examination.

    PubMed

    Fukutake, Katsunori; Ishiwatari, Takao; Takahashi, Hiroshi; Tsuchiya, Kazuaki; Okubo, Yoichiro; Shinozaki, Minoru; Tochigi, Naobumi; Wakayama, Megumi; Nemoto, Tetsuo; Shibuya, Kazutoshi; Wada, Akihito

    2015-11-21

    Ossification in the posterior longitudinal ligament (PLL) correlates with changes of enthesis during the early stages of development, but this issue remains controversial, as little is known regarding the details of this process. The aim of the present study was to elucidate part of the ossification mechanism. Thus, in the present study, we observed and evaluated minute ossifications in the PLL that did not exhibit symptoms of ossification of the posterior longitudinal ligament (OPLL). The subjects in the present study were derived from serial autopsy cases from January 2009 to December 2013 at Toho University Omori Medical Center, Japan. Minute ossifications in the PLL from autopsy subjects without any history of OPLL were screened as high-density areas using micro-focus X-ray CT, and the foci were histologically examined. Subsequently, we conducted both micro-focus X-ray CT image analysis and histological examination, and evaluated the correlation between these findings and putative predictive factors reported in previous studies. A total of 103 individuals among the 267 subjects involved in the present study were analyzed within the study period. There were no cases involving OPLL identification prior to death, and no subjects presented with neurological symptoms of myelopathy. The incidence of cases involving high-density areas greater than 0.1 mm(2) in the PLL was 46.6 %, half of which revealed mature bone structures inside this area. Thus, the high-density areas comprised three types: a continuous posterior-annular fibrosus type (23 cases), an isolated posterior-annular fibrosus type (11 cases), and a posterior-vertebral type (29 cases). However, a positive correlation was observed between the proportion of high-density areas, age (Pearson r = 0.265, p < 0.01), and HbA1c (Pearson r = 0.294, p < 0.01). Histological examination confirmed that these high-density areas involved calcification with or without mature bone formation. We evaluated

  2. Heterotopic gastric mucosa in the anus and rectum: first case report of endoscopic submucosal dissection and systematic review.

    PubMed

    Iacopini, Federico; Gotoda, Takuji; Elisei, Walter; Rigato, Patrizia; Montagnese, Fabrizio; Saito, Yutaka; Costamagna, Guido; Iacopini, Giampaolo

    2016-08-01

    Heterotopic gastric mucosa (HGM) is the most reported epithelial heterotopia, but it is very rare in the rectum and anus. The first case of an asymptomatic adult male with a large nonpolypoid HGM in the low rectum underwent complete resection by endoscopic submucosal dissection (ESD) is reported. The systematic review was based on a comprehensive search of MEDLINE, EMBASE and Google Scholar. Studies on humans were identified with the term 'heterotopic gastric mucosa in the rectum and /or anus.' The search identified 79 citations, and 72 cases were evaluated comprising the present report. Congenital malformations were observed in 17 (24%) patients; rectal duplication accounted for most of the cases. The HGM was located in the anus and perineal rectum in 25 cases (41%) and low, middle and proximal pelvic rectum in 20 (33%), five (8%) and 11 cases (18%), respectively. Morphology was nonpolypoid in 37 cases (51%), polypoid in 26 cases (36%) and ulcerated in nine cases (13%). Specific anorectal symptoms were reported by 50 (69%) patients of the whole study population, and by 33 (97%) of 34 patients ≤ 18 years. Complications were observed in 23 cases (32%). The HGM was excised in 50 cases (83%). Endoscopic resection was performed in 17 cases (34%); resection was piecemeal in five of 12 lesions ≥15 mm, required argon plasma coagulation in two cases and was associated with residual tissue in two (17%). Intestinal metaplasia and an adenoma with low-grade dysplasia were described in three adults (4%). This systematic review shows that the HGM in the rectum and anus may be associated with specific rectal symptoms and serious complications, mainly in the pediatric population, and a risk of malignancy in adults. Its complete excision should be recommended, and the ESD can overcome the technical limits of conventional endoscopic snare resection and avoid unnecessary surgery. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun

  3. Heterotopic gastric mucosa in the anus and rectum: first case report of endoscopic submucosal dissection and systematic review

    PubMed Central

    Iacopini, Federico; Gotoda, Takuji; Elisei, Walter; Rigato, Patrizia; Montagnese, Fabrizio; Saito, Yutaka; Costamagna, Guido; Iacopini, Giampaolo

    2016-01-01

    Background: Heterotopic gastric mucosa (HGM) is the most reported epithelial heterotopia, but it is very rare in the rectum and anus. Methods: The first case of an asymptomatic adult male with a large nonpolypoid HGM in the low rectum underwent complete resection by endoscopic submucosal dissection (ESD) is reported. The systematic review was based on a comprehensive search of MEDLINE, EMBASE and Google Scholar. Studies on humans were identified with the term ‘heterotopic gastric mucosa in the rectum and /or anus.’ Results: The search identified 79 citations, and 72 cases were evaluated comprising the present report. Congenital malformations were observed in 17 (24%) patients; rectal duplication accounted for most of the cases. The HGM was located in the anus and perineal rectum in 25 cases (41%) and low, middle and proximal pelvic rectum in 20 (33%), five (8%) and 11 cases (18%), respectively. Morphology was nonpolypoid in 37 cases (51%), polypoid in 26 cases (36%) and ulcerated in nine cases (13%). Specific anorectal symptoms were reported by 50 (69%) patients of the whole study population, and by 33 (97%) of 34 patients ≤ 18 years. Complications were observed in 23 cases (32%). The HGM was excised in 50 cases (83%). Endoscopic resection was performed in 17 cases (34%); resection was piecemeal in five of 12 lesions ≥15 mm, required argon plasma coagulation in two cases and was associated with residual tissue in two (17%). Intestinal metaplasia and an adenoma with low-grade dysplasia were described in three adults (4%). Discussion: This systematic review shows that the HGM in the rectum and anus may be associated with specific rectal symptoms and serious complications, mainly in the pediatric population, and a risk of malignancy in adults. Its complete excision should be recommended, and the ESD can overcome the technical limits of conventional endoscopic snare resection and avoid unnecessary surgery. PMID:27103738

  4. Erythroblast transformation-specific 2 correlates with vascular smooth muscle cell apoptosis in rat heterotopic heart transplantation model

    PubMed Central

    Liu, Xiaojuan; Yan, Daliang; Li, Yangcheng; Sha, Xilin; Wu, Kunpeng; Zhao, Jianhua; Yang, Chen; Zhang, Chao

    2016-01-01

    Background Cardiac allograft vasculopathy (CAV) decreases the long-term survival of heart transplantation recipients. Vascular smooth muscle cell (VSMC) apoptosis is an important pathological feature of CAV. Erythroblast transformation-specific 2 (Ets-2), as a transcription factor, participates in cell apoptosis and plays an important role in organ transplantation. Methods Hearts from Wistar-Furth (WF:RT1u) rats were heterotopically transplanted into Lewis (Lew:RT1l) rats without immunosuppression. Additional syngeneic heterotopic cardiac transplantations were performed in Lewis rats. HE staining was used to identify CAV. Ets-2 expression was examined by western blot. Ets-2 tissue location was examined by immunohistochemical assay and double immunostaining. Cleaved caspase 3 expression was detected by western blot. Co-localization of Ets-2 and cleaved caspase 3 was detected by double immunostaining. Ets-2, p53, cleaved caspase 3 and Bcl-xl expression in rat VSMC line A7R5 was examined after Ets-2 siRNA transfection. TUNEL assay was applied to detect A7R5 apoptosis with or without ETS-2 siRNA transfection. Immunoprecipitation was performed to explore the interaction between Ets-2 and p53. Results Ets-2 expression decreased in the allograft group but had no obvious change in the isograft group. Meanwhile, the phenomenon of CAV was observed in the allograft group and there is neointima formation in the isograft group which is not obvious compared with allograft group. Additionally, Ets-2 expression was opposite to VSMC apoptosis in the allograft group. In vitro, Ets-2 siRNA transfection in A7R5cells resulted in enhanced cell apoptosis. Finally, Ets-2 interacted with p53. Conclusions Ets-2 might inhibit VSMC apoptosis via p53 pathway. The results further elucidate the molecular mechanism of VSMC apoptosis after heart transplantation during CAV and provide theoretical basis for seeking new specific drug targets for CAV prevention and treatment. PMID:27621856

  5. Sphingosine 1-Phosphate Receptor Modulator Fingolimod (FTY720) Attenuates Myocardial Fibrosis in Post-heterotopic Heart Transplantation.

    PubMed

    Ahmed, Naseer; Linardi, Daniele; Muhammad, Nazeer; Chiamulera, Cristiano; Fumagalli, Guido; Biagio, Livio San; Gebrie, Mebratu A; Aslam, Muhammad; Luciani, Giovanni Battista; Faggian, Giuseppe; Rungatscher, Alessio

    2017-01-01

    Background and Objective: Sphingosine 1-phosphate (S1P), and S1P receptor modulator fingolimod have been suggested to play important cardioprotective role in animal models of myocardial ischemia/reperfusion injuries. To understand the cardioprotective function of S1P and its mechanism in vivo, we analyzed apoptotic, inflammatory biomarkers, and myocardial fibrosis in an in vivo heterotopic rat heart transplantation model. Methods: Heterotopic heart transplantation is performed in 60 Sprague-Dawley (SD) rats (350-400 g). The heart transplant recipients (n = 60) are categorized into Group A (control) and Group B (fingolimod treated 1 mg/kg intravenous). At baseline with 24 h after heart transplantation, blood and myocardial tissue are collected for analysis of myocardial biomarkers, apoptosis, inflammatory markers, oxidative stress, and phosphorylation of Akt/Erk/STAT-3 signaling pathways. Myocardial fibrosis was investigated using Masson's trichrome staining and L-hydroxyline. Results: Fingolimod treatment activates both Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathways as evident from activation of anti-apoptotic and anti-inflammatory pathways. Fingolimod treatment caused a reduction in myocardial oxidative stress and hence cardiomyocyte apoptosis resulting in a decrease in myocardial reperfusion injury. Moreover, a significant (p < 0.001) reduction in collagen staining and hydroxyproline content was observed in fingolimod treated animals 30 days after transplantation demonstrating a reduction in cardiac fibrosis. Conclusion: S1P receptor activation with fingolimod activates anti-apoptotic and anti-inflammatory pathways, leading to improved myocardial salvage causing a reduction in cardiac fibrosis.

  6. Specification of cerebellar progenitors after heterotopic-heterochronic transplantation to the embryonic CNS in vivo and in vitro.

    PubMed

    Carletti, Barbara; Grimaldi, Piercesare; Magrassi, Lorenzo; Rossi, Ferdinando

    2002-08-15

    The different cerebellar phenotypes are generated according to a precise time schedule during embryonic and postnatal development. To assess whether the differentiative potential of cerebellar progenitors is progressively restricted in space and time we examined the fate of embryonic day 12 (E12) or postnatal day 4 (P4) cerebellar cells after heterotopic-heterochronic transplantation into the embryonic rat brain in utero or into organotypic CNS explants in vitro. Donor cells, isolated from transgenic mice overexpressing the enhanced-green fluorescent protein under the control of the beta-actin-promoter, engrafted throughout the host brainstem and diencephalon, whereas they rarely incorporated into specific telencephalic structures. In any recipient site, the vast majority of transplanted cells could be recognized as cerebellar phenotypes, and we did not obtain clear evidence that ectopically located cells adopted host-specific identities. Nevertheless, the two donor populations displayed different developmental potentialities. P4 progenitors exclusively generated granule cells and molecular layer interneurons, indicating that they are committed to late-generated cerebellar identities and not responsive to heterotopic-heterochronic environmental cues. In contrast, E12 precursors had the potential to produce all major cerebellar neurons, but the repertoire of adult phenotypes generated by these cells was different in distinct host regions, suggesting that they require instructive environmental information to acquire mature identities. Thus, cerebellar precursors are able to integrate into different foreign brain regions, where they develop mature phenotypes that survive long after transplantation, but they are committed to cerebellar fates at E12. Embryonic progenitors are initially capable, although likely not competent, to generate all cerebellar identities, but their potential is gradually restricted toward late-generated phenotypes.

  7. 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.

  8. Compression Angle of Ossification of the Posterior Longitudinal Ligament and Its Clinical Significance in Cervical Myelopathy

    PubMed Central

    Lee, Nam; Yoon, Do Heum; Kim, Keung Nyun; Shin, Hyun Chul; Shin, Dong Ah

    2016-01-01

    Objectives The correction of clinical and radiologic abnormalities in patients with symptomatic ossification of the posterior longitudinal ligament (OPLL) is the current mainstay of treatment. This study aimed to identify radiographic predictors of severity of myelopathy in patients with symptomatic OPLL. Methods Fifty patients with symptomatic cervical OPLL were enrolled. Based on Japanese Orthopedic Association (JOA) scores, patients were divided into either the mild myelopathy (n=31) or severe myelopathy (n=19) group. All subjects underwent preoperative plain cervical roentgenogram, computed tomography (CT), and MR imaging (MRI). Radiological parameters (C2–7 sagittal vertical axis, SVA; C2–7 Cobb angle; C2–7 range of motion, ROM; OPLL occupying ratio; and compression angle) were compared. Compression angle of OPLL was defined as the angle between the cranial and caudal surfaces of OPLL at the maximum level of cord compression Results The occupying ratio of the spinal canal, C2–7 Cobb angle, C2–7 SVA, types of OPLL, and C2–7 ROM of the cervical spine were not statistically different between the two groups. However, the OPLL compression angle was significantly greater (p=0.003) in the severe myelopathy group than in the mild myelopathy group and was inversely correlated with JOA score (r=-0.533, p<0.01). Furthermore, multivariate regression analysis demonstrated that the compression angle (B=-0.069, p<0.001) was significantly associated with JOA scores (R=0.647, p<0.005). Conclusion Higher compression angles of OPLL have deleterious effects on the spinal cord and decrease preoperative JOA scores. PMID:27651865

  9. The iliac crest in forensic age diagnostics: evaluation of the apophyseal ossification in conventional radiography.

    PubMed

    Wittschieber, Daniel; Vieth, Volker; Domnick, Christoph; Pfeiffer, Heidi; Schmeling, Andreas

    2013-03-01

    Due to the increasing significance of forensic age estimations in the age of globalisation, novel radiographic criteria besides clavicles and hand bones may provide additional certainty for forensic age expertises. The present study analyses the suitability of the iliac crest apophysis by means of 643 pelvic radiographs of patients between 10 and 30 years of age. Retrospective assessments were carried out according to the forensically established classification and sub-classification systems modified after Kreitner et al. (Rofo 166(6):481-486, 1997) and Kellinghaus et al. (Int J Legal Med 124(4):321-325, 2010). The basic ossification stages range from 1 to 4, and the sub-stages of stage 2 and 3 range from a to c. While stage 3c was first achieved at the age of 15 by both sexes, stage 4 was first observed in females at the age of 16 and in males at the age of 17. This indicates the possibility of a valid diagnosis of both the age of 14 and the age of 16 years which represent legally relevant age thresholds in numerous countries. Applied as targeted radiography on the iliac crest, the exposure to radiation would range between other radiographic techniques recently applied. Therefore, the iliac crest apophysis appears principally suitable as novel possible criterion for forensic age estimation in the living. However, for the establishment of the iliac crest apophysis in routine diagnostics, further studies are needed focussing on the comparison of different grading systems and different radiological techniques.

  10. Spinal cord morphology and pathology in ossification of the posterior longitudinal ligament.

    PubMed

    Kameyama, T; Hashizume, Y; Ando, T; Takahashi, A; Yanagi, T; Mizuno, J

    1995-02-01

    We analysed nine autopsy cases of ossification of the posterior longitudinal ligament (OPLL) to elucidate the relationship between morphology and pathology of the spinal cord. The cross-sectional shape of the spinal cord at the most severely affected segment was classified into two categories: boomerang (convex lateral surfaces and concave anterior surface) and triangular (angular lateral surfaces and flat anterior surface). In the cases with a boomerang shape, even when the compression was severe, major pathological changes were restricted to the grey matter and the white matter was relatively well preserved. No secondary descending degeneration of the lateral columns was seen, and ascending degeneration of the posterior column was restricted to the fasciculus cuneatus whose fibres were derived from the affected segments. In the cases with a triangular shape, pathological changes were more severe, both white matter and grey matter were involved, and only the anterior columns were free of pathological changes. There were severe pathological changes over more than one segment, and both descending degeneration of the lateral pyramidal tracts and ascending degeneration of the posterior column, including the fasciculus gracilis, were observed. The transverse area of the spinal cord was > 60% of normal in most of the cases with a boomerang shape, but it was reduced to < 60% of normal in more than one segment in the cases with a triangular shape. The compression ratio of the spinal cord (sagittal diameter/transverse diameter x 100%) was not related to pathological changes. In conclusion, a triangular-shaped spinal cord with transverse area of < 60% of normal in more than one segment appeared to be associated with severe and irreversible pathological changes in cases of OPLL.

  11. Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing.

    PubMed

    Holstein, Joerg H; Menger, Michael D; Scheuer, Claudia; Meier, Christoph; Culemann, Ulf; Wirbel, Rainer J; Garcia, Patric; Pohlemann, Tim

    2007-02-13

    Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analysis. Thirty-six SKH1-hr mice were treated with daily i.p. injections of 5000 U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks of fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6+/-19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5+/-7.1%) when compared to vehicle-treated controls (14.3+/-8.2% and 105.9+/-6.6%; p<0.05). Accordingly, the histomorphometric examination revealed an increased fraction of mineralized bone and osteoid (33.0+/-3.0% versus 28.5+/-3.6%; p<0.05). Of interest, this early effect of the initial 6-day EPO treatment had vanished at 5 weeks after fracture. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.

  12. Spinal Cord Kinking in Thoracic Myelopathy Caused by Ossification of the Ligamentum Flavum

    PubMed Central

    Wang, Ting; Pan, Min; Yin, Chu-Qiang; Zheng, Xiu-Jun; Cong, Ya-Nan; Wang, De-Chun; Li, Shu-Zhong

    2015-01-01

    Background: Ossification of the ligamentum flavum (OLF) is being increasingly recognized as a cause of thoracic myelopathy. This study was to describe a rare clinical entity of spinal cord kinking (SK) in thoracic myelopathy secondary to OLF. Methods: The data of 95 patients with thoracic myelopathy secondary to OLF were analyzed retrospectively. The incidence and location of SK were determined using preoperative magnetic resonance imaging (MRI). The clinical presentation and radiological characteristics in patients with SK were analyzed. Posterior en bloc laminectomy with OLF was performed, and the surgical results were evaluated. Results: SK was found in seven patients (7.4%) based on preoperative MRI. The patients included one male and six females with an average age of 55.6 years (range, 48–64 years). Five patients presented with radiculomyelopathy and two presented with typical thoracic myelopathy of spastic paraparesis. In all cases, the kinking was located just above the end of the spinal cord where the conus medullaris (CM) was compressed by the OLF. The degree of SK varied from mild to severe. The tip of the CM was located between the upper third of T11 to the lower third of L1, above the lower edge of L1. With an average follow-up of 30.4 months, the modified Japanese Orthopedic Association score significantly improved from 5.7 ± 1.8 preoperatively to 8.9 ± 1.4 postoperatively (t = 12.05; P < 0.0001) with an improvement rate of 63.1 ± 12.3%. Conclusions: SK is a rare radiological phenomenon. It is typically located at the thoracolumbar junction, where the CM is compressed by the OLF. Our findings indicate that these patients may benefit from a posterior decompressive procedure. PMID:26415796

  13. Dysregulation of ossification-related miRNAs in circulating osteogenic progenitor cells obtained from patients with aortic stenosis

    PubMed Central

    Takahashi, Kan; Takahashi, Yuji; Osaki, Takuya; Nasu, Takahito; Tamada, Makiko; Okabayashi, Hitoshi; Nakamura, Motoyuki; Morino, Yoshihiro

    2016-01-01

    CAVD (calcific aortic valve disease) is the defining feature of AS (aortic stenosis). The present study aimed to determine whether expression of ossification-related miRNAs is related to differentiation intro COPCs (circulating osteogenic progenitor cells) in patients with CAVD. The present study included 46 patients with AS and 46 controls. Twenty-nine patients underwent surgical AVR (aortic valve replacement) and 17 underwent TAVI (transcatheter aortic valve implantation). The number of COPCs was higher in the AS group than in the controls (P<0.01). Levels of miR-30c were higher in the AS group than in the controls (P<0.01), whereas levels of miR-106a, miR-148a, miR-204, miR-211, miR-31 and miR-424 were lower in the AS group than in the controls (P<0.01). The number of COPCs and levels of osteocalcin protein in COPCs were positively correlated with levels of miR-30a and negatively correlated with levels of the remaining miRNAs (all P<0.05). The degree of aortic valve calcification was weakly positively correlated with the number of COPCs and miR-30c levels. The number of COPCs and miR-30c levels were decreased after surgery, whereas levels of the remaining miRNAs were increased (all P<0.05). Changes in these levels were greater after AVR than after TAVI (all P<0.05). In vitro study using cultured peripheral blood mononuclear cells transfected with each ossification-related miRNA showed that these miRNAs controlled levels of osteocalcin protein. In conclusion, dysregulation of ossification-related miRNAs may be related to the differentiation into COPCs and may play a significant role in the pathogenesis of CAVD. PMID:27129184

  14. Heterotopic pancreas in Meckel's diverticulum in a 7-year-old child with intussusception and recurrent gastrointestinal bleeding: case report and literature review focusing on diagnostic controversies.

    PubMed

    Riccardo, Guanà; Valeria, Bucci; Giulia, Carbonaro; Alessia, Cerrina; Luisa, Ferrero; Elisabetta, Teruzzi; Alessandro, Mussa; Isabella, Morra; Jürgen, Schleef

    2014-01-01

    Meckel's diverticulum, the most common congenital abnormality of the small intestine, may be associated to heterotopic pancreas, often diagnosed incidentally on histopathological examination. Intussusception affects infants between the ages of 5 and 9 months, but it may also occur in older children, teenagers and adults, and in some cases can be derived by a Meckel's diverticulum resulting in acute abdomen. We analyse the management and the recent literature on similar cases, describing diagnostic options. In May 2013, a 7-year-old girl admitted to our hospital with recurrent gastrointestinal bleeding, was discovered to have an ileoileal intussusception with a leading Meckel's diverticulum with heterotopic pancreatic tissue. This association is rare evidence in children and its proper management can be controversial, in particular from a diagnostic point of view. In such cases, preoperative radiological diagnosis can be only suspected in the presence of suggestive signs, more often depicted by ultrasound or computed tomography scan. During laparotomy an accurate exploration of all ileum is recommended, for the possibility to find others heterotopic segments.

  15. The use of postoperative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: An animal model

    SciTech Connect

    Konski, A.; Weiss, C.; Rosier, R.; Poulter, C.; Pelligrini, V.; Anthony, P.; Evarts, C.M.; Richardson, M.; Henzler, M.; Rubin, P. )

    1990-04-01

    Radiation has been shown to be effective in the prevention of heterotopic bone. The exact etiology of heterotopic bone is unknown. Total hip prosthetic devices that do not depend upon bone cement for fixation have become increasingly popular. The mechanism by which the bone forms around the prosthesis is similar to the process by which fractures heal which has been shown to be sensitive to irradiation. Using a rabbit model we have undertaken a study to investigate the effect of irradiation on the bony ingrowth on porous coated implants. Forty-five rabbits had porous coated implants surgically placed in the tibiae bilaterally. Each rabbit had one tibia randomly irradiated with 1,000 cGy in 5 fractions starting on the first post-operative day. Animals were sacrificed weekly starting 2 weeks post-operatively and the tibae were sent for pullout studies. The amount of force necessary to pullout the treated tibae was statistically less than the amount of force necessary to remove the untreated tibae at 2 weeks. From 3 weeks on there was no difference in the force necessary to remove the prosthesis from the untreated or treated tibae. Histologically, the untreated tibae showed bone formation while the treated tibae did not. Because of these results, it is suggested that the treatment of patients at risk for development of heterotopic bone be modified to only include the area between the femur and pelvis avoiding treatment of the prosthetic device.

  16. Carcinoid tumor of the lung with massive ossification: report of a case showing the evidence of osteomimicry and review of the literature.

    PubMed

    Tsubochi, Hiroyoshi; Endo, Shunsuke; Oda, Yoshinao; Dobashi, Yoh

    2013-01-01

    Carcinoid tumor is one of the commonly encountered primary pulmonary neoplasms. Although it has been known to be accompanied by calcification and/or ossification, presentation with a large ossified mass is rare. We describe here the case of a 29-year-old female with the radiological finding of a single bony nodular lesion. Pathological examination of the surgically resected specimen led to the diagnosis of carcinoid tumor of the lung with massive ossification. Although histological features showed the tumor of low grade malignancy, subcarinal and right hilar lymph nodes were found to be positive for metastasis. Further immunohistochemical analysis revealed that the tumor cells expressed the osteogenic inducer protein, bone morphogenic protrein-2 [BMP-2] and osteoblastic marker protein, osteocalcin. We interpreted this to mean that the carcinoid tumor cells had acquired an osteoblastic phenotype and had subsequently developed marked intratumoral ossification. The relevant literature is reviewed and possible mechanisms of tumor-related osteogenesis are discussed.

  17. 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.

  18. Assessment of the three-dimensional relationship of the ossific nuclei and cartilaginous anlagen in congenital clubfoot by 3-D MRI.

    PubMed

    Itohara, Tomonobu; Sugamoto, Kazuomi; Shimizu, Nobuyiki; Ohno, Ikko; Tanaka, Hisashi; Nakajima, Yoshikazu; Sato, Yoshinobu; Yoshikawa, Hideki

    2005-09-01

    Radiographic measurement is the usual method used to objectively determine the extent of a congenital clubfoot deformity. Although radiographs have been used clinically to estimate the size and location of tarsal bones through measurements of the ossific nuclei, it is not clear to what extent these relationships are actually reflected in these measurements. So, we used a 3-D MRI system that could more objectively estimate sizes and positional relationships. We evaluated 5 patients with unilateral congenital clubfoot deformity. Magnetic resonance imaging was performed of both feet using 1.5-T magnet. Based on the resulting magnetic resonance imaging volume data, a three-dimensional surface bone model was reconstructed by the Marching Cubes method. We used this model to perform a comparative analysis of the volume and volume ratio of each cartilaginous anlage and ossific nucleus, the length of the talus and the calcaneus, and the position of the center of gravity of ossific nuclei within the cartilaginous anlagen. We measured the relationship between the ossific nuclei and cartilaginous anlagen in the talus and calcaneus of patients with unilateral clubfoot deformity. In clubfeet talus volume was reduced by 20.1% and calcaneal volume was reduced by 15.7%. Furthermore, the volume of the talar ossific nucleus was reduced by 42.6% and that of the calcaneal ossific nucleus was reduced by 12.1%. The length of the clubfoot talus was 8.2% shorter than normal, and that of the calcaneus was 4.8% shorter. The assessment technique presented herein was shown to be useful in ascertaining the various pathological characteristics associated with clubfoot.

  19. [Radical tumour resection in the upper extremity and heterotopic replantation of the hand. Analyses of functional results in two patients].

    PubMed

    Piza-Katzer, H; Baur, E-M; Estermann, D

    2008-10-01

    We describe here two cases treated 17 years apart from each other. The patients were young males with malignant soft tissue tumours of the forearm and elbow joint. Radical tumour resection involved removal of the elbow joint. Neither of the patients consented to upper arm amputation, but agreed to undergo heterotopic replantation of the amputated distal third of the forearm together with the hand to the stump of the upper arm. The tendons of the forearm were attached to the three muscles of the upper arm, and the distal nerves were coapted with the nerve trunks of the upper arm. However, the reconstructive procedures carried out in these two patients were anatomically different. In the first patient, for technical reasons, only the deep flexor tendons were sutured. Furthermore, development of a postoperative haematoma necessitated revision surgery with split-thickness skin graft to cover the defect of the forearm. Long-term immobilisation together with a conservative approach to mobility had resulted in less than optimal results so that it appeared meaningful to re-operate the patient even 17 years after the primary operation to help him gain improved sensibility as well as motor function. These goals were achieved to a surprising extent by scar release, Z-plasty, removal of split-thickness skin graft, neurolysis, arthrodesis of the IP joint of the thumb, and tendon transposition together with intensive early postoperative sensibility and mobility training. In the second patient, longitudinal division of the muscles of the upper arm into different compartments and interweaving of the long tendons of the forearm into these muscles as well as early intensive mobility training and reintegration of the replanted hand in the body scheme resulted in the rapid gain of extremely good functional results so that the patient is now able to employs his heterotopically replanted hand quite effectively in his activities of daily living as a farmer. We believe that the

  20. Effects of heterotopic noxious stimuli on activity of neurones in subnucleus reticularis dorsalis in the rat medulla.

    PubMed Central